Efeitos da N(épsilon)-(carboximetil)lisina (CML), um produto final de glicação avançada (PFGA), na doença falciforme

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-08T17:17:43Z No. of bitstreams: 1 Uche Samuel Ndidi Efeitos da N(Epsilon) (carboximetil)... 2018.pdf: 2753856 bytes, checksum: 3be25d0eb36e2c3f8e7a8c6bc60febaf (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-08T17:44:39Z (GMT) No. of bitstreams: 1 Uche Samuel Ndidi Efeitos da N(Epsilon) (carboximetil)... 2018.pdf: 2753856 bytes, checksum: 3be25d0eb36e2c3f8e7a8c6bc60febaf (MD5)Made available in DSpace on 2018-08-08T17:44:39Z (GMT). No. of bitstreams: 1 Uche Samuel Ndidi Efeitos da N(Epsilon) (carboximetil)... 2018.pdf: 2753856 bytes, checksum: 3be25d0eb36e2c3f8e7a8c6bc60febaf (MD5) Previous issue date: 2018CNPq, FAPESB, FIOCRUZ-IGMFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.A doença falciforme (DF) caracteriza-se pela presença da hemoglobina S, que pode estar em homozigose (HbSS), como na anemia falciforme (AF), bem como em associação com outras hemoglobinas variantes ou talassemias, como na doença SC (HbSC). A HbS forma agregados em estado de desoxigenação, com consequente rigidez eritrocitária, fatores que contribuem para alterações na microvasculatura, resultando em vaso-oclusão, isquemia tecidual, lesão de órgãos, eventos dolorosos e compromentimento crônico de vários orgãos e sistemas. A gravidade da vaso-oclusão e a progressão para isquemia do órgão terminal são potencializadas pelo estresse oxidativo, sendo que os produtos finais de glicação avançada (PFGAs), tais como N(épsilon)carboximetilisina (CML), constituem marcadores desse processo de oxidação. -OBJETIVO: O objetivo geral do presente estudo foi determinar os níveis de CMLs no soro de pacientes com DF (HbSS e HbSC), bem como associar essas concentrações a biomarcadores laboratoriais e genéticos, bem como ao tratamento com a hidroxiuréia (HU). MATERIAIS E MÉTODOS: Os testes hematológicos foram realizados em contador de células automatizado; os marcadores bioquímicos foram mensurados no soro por ensaio de imunoquímica. Os perfiis de hemoglobina foram confirmados por cromatografia líquida de alta eficiência (HPLC). Os haplótipos associados ao grupo de genes da globina beta S (HBB S) e genes da globina beta C (HBB C) foram investigados por reação em cadeia da polimerase, seguida da análise de polimorfismos de comprimento de fragmentos de restrição (RFLP). Os níveis séricos de CML foram avaliados por ELISA competitivo. As análises estatísticas foram realizadas utilizando-se os softwares SPSS e GraphPad, considerando p≤0,05 como estatisticamente significante. RESULTADOS: O presente estudo demonstra a existência de características laboratoriais distintas nos indivíduos com AF em tratamento com HU em comparação aos sem tratamento. Em resumo, o estudo demonstrou que o tratamento com HU reduziu a anemia hemolítica aguda e as crises vaso-oclusivas. Em relação aos níveis de CML, foi demonstrado que os indivíduos com AF apresentaram concentrações mais elevadas no soro, em comparação aos controles saudáveis (HbAA). Foi identificada a correlação significativa entre alanina aminotransferase (ALT) e CML. Demonstrou ainda que a CML está associada ao haplótipo βS em pacientes com AF e evidenciou que os níveis de CML estiveram mais elevados nos pacientes com doença SC em comparação com os controles saudáveis e também revelou anemia hemolítica, crises de dor e hipocolesterolemia em pacientes com HbSC em comparação com o controle saudável. CONCLUSÃO: Nossos resultados sugerem que a HU parece influenciar a inflamação, hemólise e função hepática dos pacientes com AF. As evidências do presente estudo sugerem a possibilidade de que os CMLs tenham papel na patologia da DF, com associação aos haplótipos da globina beta, nas complicações presentes na AF, mas que os seus níveis séricos não são influenciados pelo tratamento com HU.Sickle cell disease (SCD) is characterized by the presence of hemoglobin S, which may be homozygous (HbSS), like in sickle cell anemia (SCA), as well as in association with other variant hemoglobins or thalassemias, such as SC (HbSC). HbS forms aggregates in a state of deoxygenation, with consequent erythrocyte rigidity, factor that contribute to changes in the microvasculature, resulting in vaso-occlusion, tissue ischemia, organ damage, pain and chronic compromise of various organs and systems. The severity of the vaso-occlusion and progression to end organ ischemia is potentiated by oxidative stress and advanced glycation end-products (AGEs) such as N(epsilon)-carboxymethylisine (CML) have been demonstrated to be markers of oxidative stress. OBJECTIVE: The general objective of the present study was to determine serum CML levels in patients with SCD (HbSS and HbSC), as well as to associate their concentrations with laboratory and genetic biomarkers, as well as with hydroxyurea (HU) treatment. MATERIALS AND METHODS: Hematological tests were performed in an automated cell counter; the biochemical markers were measured in the serum by immunochemistry assay. Hemoglobin profiles were confirmed by high performance liquid chromatography (HPLC). The haplotypes associated with the beta globin gene cluster (HBB S) and beta globin C (HBB C) genes were investigated by polymerase chain reaction, followed by restriction fragment length polymorphism (RFLP) analysis. Serum levels of CML were evaluated by competitive ELISA. Statistical analyzes were performed using the software SPSS and GraphPad, considering p ≤ 0.05 as statistically significant. RESULTS: The present study demonstrates the existence of distinct laboratory characteristics in individuals with SCA on HU treatment compared to those without treatment. In summary, the study demonstrated that treatment with HU reduced acute hemolytic anemia and vaso-occlusive crises. Regarding CML levels, individuals with SCA presented higher serum concentrations than healthy controls (HbAA). Significant correlation between alanine aminotransferase (ALT) and CML was identified. It also showed that CML is associated with βS haplotype in patients with SCA and that CML levels were higher in patients with SC disease compared to healthy controls. Hemolytic anemia, pain crises and hypocholesterolemia were identified in individuals with HbSC compared to healthy control. CONCLUSION: Our results suggest that HU plays a significant role in inflammation, hemolysis, and hepatic systems in sickle cell anemia. The evidences of the present study suggest the possibility that CMLs have a role in the pathology of SCD. It also suggests an association between CML and SCA haplotypes, and has shown that CML has a role to play in the complications of SCA that is not influenced by HU treatment

Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin–induced diabetic albino rats

Objective: To test two water soluble extracts (aqueous and ethanolic) obtained from the leaves of Vitex doniana in normal and streptozotocin-induced diabetic rats for their effects on pancreatic endocrine tissues and serum marker enzymes for a period of 21 d. Methods: A total of 55 rats divided into 11 groups of 5 rats each were assigned into diabetic and non-diabetic groups and followed by a daily administration of ethanolic and aqueous extracts for 21 d. Group 1 was the normal control while group 7 was treated with standard drug. Results: The histopathological studies of the diabetic rats indicated increase in the volume density of islets, percent of β-cells and size of islet in the groups that received the plant extracts, which suggested regeneration of β-cells along with β-cells repairs, as compared with the non-treated diabetic control which showed complete degeneration of the islet cells. There was significant reduction (P0.01) in the serum activities of marker enzymes was observed for non-diabetic treated rats. Results of total bilirubin, direct bilirubin and unconjugated bilirubin showed that diabetic control group was significantly higher (P0.01) in total bilirubin and direct bilirubin compared with the normal control. Conclusions: This herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat

Association Between Dietary Pattern And Severity Of Pain Crisis In Adolescents With Sickle Cell Anaemia Attending A Tertiary Health Facility In Northwestern Nigeria

Background: Sickle cell anaemia is an inherited chronic disease with clinical manifestations arising from polymerization of haemoglobin leading to the deformity of red blood cells into a sickled shape.Objective: This study assessed the dietary pattern and severity of pain crisis in adolescents with sickle cell anaemia.Methods: The study design was a cross-sectional survey. Fifty consenting participants with a diagnosis of sickle cell anaemia aged 10 to 19 years were enrolled in this study. Severity of pain crisis was evaluated using a modified Wong-Baker's Pain Scale. Food frequency questionnaire was used to obtain food consumption patterns. Data generated was analyzed using Statistical Package for Social Sciences (SPSS) software. Cross tabulation and Chi-square were used to determine relationships between variables and statistical significance was established at p<0.05.Results: All the participants were single with 54 % (n/50) female and 60 % (n/50) of them had at least secondary education. Mean age of participants was 14.3±2.8years. Adolescents who had no pain crisis were 28 % (n/N) while 42 % (n/N), 18 % (n/N) and 12 % (n/N), had mild, moderate and severe pain respectively. Dietary pattern consisted mostly of cereals, roots and tubers, milk and milk products consumed with vegetables being the least consumed. Roots and tubers, milk and milk products showed significant negative relationship with pain severity (p=0.025 and p=0.019 respectively) while meal skipping showed significant positive relationship with severity pain (p=0.034).Conclusion: Poor dietary practices was associated with the severity of pain crisis of the adolescents living with SCA

Effects of aqueous extracts of <i>Acacia albida</i> stem bark on Wistar albino rats infected with <i>Trypanosoma evansi</i>

<div><p>The effect of aqueous extract of <i>Acacia albida</i> stem bark was investigated in Wistar albino rats infected with <i>Trypanosoma evansi</i>. The extract showed highest reduction in parasitemia at the dose of 600 mg/kg body weight (bw). A dose of 300 mg/kg bw improved packed cell volume the most by 14.35%. The group treated with 150 and 600 mg/kg bw of the extract showed significant decrease (<i>P</i> < 0.05) in alanine transaminase and aspartate transaminase levels which were lower than those of the group treated with diminazene aceturate. The group treated with 150 mg/kg bw of the extract showed the least urea, albumin and protein level and lowest relative organ weight. There was a significant difference (<i>P</i> < 0.05) in the levels of catalase and Thiobarbituric acid reactive substances in liver and kidney of the animals in the infected-untreated group and the extracts-treated groups. The results of this study show that the extracts of <i>A. albida</i> have antitrypanosomal activity against <i>T. evansi</i> infection.</p></div

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

Effect of N(Epsilon)-(carboxymethyl)lysine on Laboratory Parameters and Its Association with βS Haplotype in Children with Sickle Cell Anemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-11-18T16:34:02Z No. of bitstreams: 1 Ndidi, U. S. Effect....pdf: 5542454 bytes, checksum: fa2a3b16136b031175a4ffa17f0265f6 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-11-18T16:54:02Z (GMT) No. of bitstreams: 1 Ndidi, U. S. Effect....pdf: 5542454 bytes, checksum: fa2a3b16136b031175a4ffa17f0265f6 (MD5)Made available in DSpace on 2019-11-18T16:54:03Z (GMT). No. of bitstreams: 1 Ndidi, U. S. Effect....pdf: 5542454 bytes, checksum: fa2a3b16136b031175a4ffa17f0265f6 (MD5) Previous issue date: 2019Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant 154419/2014-1 to MSG) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES) (Finance Code 001 to RPS and SCMAY) for their financial support.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Ahmadu Bello University. Department of Biochemistry. Zaria, Nigeria.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 Anemias. Departamento de Análises Clínicas e Toxicologicas. 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 Anemias. Departamento de Análises Clínicas e Toxicologicas. 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 Anemias. Departamento de Análises Clínicas e Toxicologicas. 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 Anemias. Departamento de Análises Clínicas e Toxicologicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemias. Departamento de Análises Clínicas e Toxicologicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemias. Departamento de Análises Clínicas e Toxicologicas. Salvador, BA, Brasil.Fundação de Hematologia e Hemoterapia da Bahia. Salvador, BA, Brasil.Kuwait University. Faculty of Medicine. Department of Pediatrics. Kuwait.Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemias. Departamento de Análises Clínicas e Toxicologicas. 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 Anemias. Departamento de Análises Clínicas e Toxicologicas. Salvador, BA, Brasil.The present study aimed to investigate the association of Nε-carboxymethyllysine (CML) with laboratory parameters and βS haplotypes in pediatric sickle cell anemia (SCA) patients with or without hydroxyurea (HU) therapy. We included 55 children with SCA (SCAtotal), where 27 were on HU treatment (SCA-HU+) and 28 without HU treatment (SCA-HU-). Laboratory characteristics were determined using electronic methods while CML was measured using competitive ELISA. βS haplotypes were determined by RFLP-PCR. Significant increases in MCV and MCH and significant decreases in leukocytes, eosinophils, basophils, atypical lymphocytes, lymphocytes, and monocytes were found in SCA-HU+ compared to SCA-HU-. SCA-HU+ presented significant reduction in aspartate transaminase and lactate dehydrogenase and increase in creatinine levels compared to SCA-HU-. CML levels were significantly higher in both SCA-HU+ and SCA-HU- compared to the healthy control. In addition, a negative correlation was found between CML and alanine transaminase in SCA-HU+ and SCAtotal (p < 0 01). A significant association was found between CML levels and βS haplotypes. The results suggest that CML has a role to play in SCA complications, independent of HU therapy

Hydroxyurea alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with βS haplotype and α-thalassemia.

This study investigated the effects of hydroxyurea (HU) on hematological, biochemical and inflammatory parameters in children with sickle cell anemia (SCA) in association with βS haplotype and α-thalassemia. We included 22 children with SCA who were followed for an average of 14.5 months. Laboratory parameters were assessed by electronic methods, and molecular analysis was investigated by PCR-RFLP and allele-specific PCR. Results showed significant increases in hemoglobin, HbF, hematocrit, MCV, MCH, glucose, HDL-C and albumin levels, as well as significant decreases in MCHC and AST levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes, in children during HU therapy. HbF levels were positively correlated with hemoglobin, hematocrit, MCV and total protein, yet negatively correlated with MCHC, RDW, AAT and AST during HU therapy (p<0.05). Children who carried the Central African Republic haplotype, in response to HU therapy, presented significant increases in hemoglobin, hematocrit, triglycerides and uric acid levels, as well as significant decreases in MCHC, AST and direct bilirubin levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes. Those with the Benin haplotype presented increases in HbF and albumin levels, and a reduction in platelet counts (p<0.05). Children with α-thalassemia presented decreased ALT during HU use, while those without this deletion presented increases in hemoglobin, hematocrit, MCV, MCH, HDL-C and albumin, as well as decreases in MCHC, neutrophils, lymphocytes, reticulocytes and AST (p<0.05). Hence, regardless of its use in association with βS haplotypes or α-thalassemia, HU seems to be linked to alterations in hemolytic, inflammatory, hepatic, lipid and glycemic profiles

Sickle cell disease: A distinction of two most frequent genotypes (HbSS and HbSC).

Sickle cell disease (SCD) consists of a group of hemoglobinopathies in which individuals present highly variable clinical manifestations. Sickle cell anemia (SCA) is the most severe form, while SC hemoglobinopathy (HbSC) is thought to be milder. Thus, we investigated the clinical manifestations and laboratory parameters by comparing each SCD genotype. We designed a cross-sectional study including 126 SCA individuals and 55 HbSC individuals in steady-state. Hematological, biochemical and inflammatory characterization was performed as well as investigation of previous history of clinical events. SCA patients exhibited most prominent anemia, hemolysis, leukocytosis and inflammation, whereas HbSC patients had increased lipid determinations. The main cause of hospitalization was pain crises on both genotypes. Vaso-occlusive events and pain crises were associated with hematological, inflammatory and anemia biomarkers on both groups. Cluster analysis reveals hematological, inflammatory, hemolytic, endothelial dysfunction and anemia biomarkers in HbSC disease as well as SCA. The results found herein corroborate with previous studies suggesting that SCA and HbSC, although may be similar from the genetic point of view, exhibit different clinical manifestations and laboratory alterations which are useful to monitor the clinical course of each genotype