28 research outputs found
Efeitos da N(épsilon)-(carboximetil)lisina (CML), um produto final de glicação avançada (PFGA), na doença falciforme
No full textA 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.CNPq, FAPESB, FIOCRUZ-IGMSickle 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.2021-07-0
Efeitos da N(épsilon)-(carboximetil)lisina (CML), um produto final de glicação avançada (PFGA), na doença falciforme
No full textCNPq, 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.2021-07-0
Insights on Phytomonas: A Bibliometric Analysis on Global Research Outputs Highlighting Research Gaps and Future Directions
No full textThe study aims to access the research output on Phytomonas from inception to 2023 using bibliometric science mapping and visualization tools. We analyzed the distribution of publications retrieved from the Scopus database, categorized topics, and tracked progress over time. Additionally, we examined country contributions and author collaboration (co-authorship), with particular emphasis on research topics and emerging research areas. We also highlighted the paucity of research from Australia, Africa, and Asia, where Phytomonas could be a major parasite affecting important crops
Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin–induced diabetic albino rats
No full textABSTRACTObjectiveTo 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.MethodsA 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.ResultsThe 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 (P<0.05) in the serum activities of marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in diabetes treated rats, whereas an insignificant increase (P>0.01) 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 (P<0.05) in total bilirubin and unconjugated bilirubin compared with treated groups while non-diabetic treated groups showed no significant increase (P>0.01) in total bilirubin and direct bilirubin compared with the normal control.ConclusionsThis herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat
<i>In vitro</i> antitrypanosomal and antioxidant activities of methanol extracts of selected Nigerian plants
No full textPhytochemical and Antitrypanosomal Studies of Different Solvents Extracts of Boswellia dalzielii
No full textAssociation Between Dietary Pattern And Severity Of Pain Crisis In Adolescents With Sickle Cell Anaemia Attending A Tertiary Health Facility In Northwestern Nigeria
No full textBackground: 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>
No full text<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
No full textFundação 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
Structure, mutation, functional domain roles and medical implications of glycerol kinase
No full textGlycerol kinase (GK) is a key part of glycerol metabolism. It connects the metabolic pathways for lipids and carbohydrates by phosphorylating glycerol to glycerol-3-phosphate in an ATP-dependent reaction. This is essential for maintaining carbohydrate homeostasis, plasma glycerol withdrawal, and the utilization of glycerol by different tissues. Together, these processes impact glucose uptake and lipid metabolism. This review discusses the structure of GK, highlights the implications of mutations in the primary sequence, and provides insights on the roles of the various functional domains in the GK-catalyzed reaction. It also discussed the roles of GK in glycerol metabolism, energy production, and its connections with various cellular pathways and disease conditions. The proper regulation of GK activity is crucial, reflecting its critical role in various important cellular processes. Therefore, its regulation has been analyzed from the gene level to posttranslational modification and has implications for GK-linked disease. Separately, the critical role of this enzyme in some disease-causing organisms made it a promising target for inhibitor development. We here explore the current state of GK inhibitor research and discuss strategies for their development. Challenges in GK inhibitor research are identified, and approaches such as high-throughput screening, structure-based drug design, and computational modelling for discovering novel inhibitors are reviewed. Finally, the review highlights critical areas for further research, including the role of GK in synthetic biology and tumour development, among others
