RESUMO
Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid levels and the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing inhibition remain elusive. In a quest to elucidate these mechanisms, we conducted a molecular dynamics simulation approach followed by a Raman spectroscopy study to delve into the intricate interplay between the folic acid metabolite, 7,8-dihydrofolate (DHF), and the angiotensin-converting enzyme ACE2 receptor, coupled with its interaction with the receptor-binding domain (RBD) of the Wuhan strain of SARS-CoV-2. Through a meticulous exploration, we scrutinized the transformation of the ACE2 + RBD complex, allowing these reactants to form bonds. This was juxtaposed with a similar investigation where ACE2 was initially permitted to react with DHF, followed by the exposure of the ACE2 + DHF complex to RBD. We find that DHF, when bonded to ACE2, functions as a physical barrier, effectively inhibiting the binding of the Wuhan strain RBD. This physicochemical process offers a cogent explanation for the observed inhibition of host cell infection in subjects receiving supplementary folic acid doses, as epidemiologically substantiated in multiple studies. This study not only sheds light on a potential avenue for mitigating SARS-CoV-2 infection but also underscores the crucial role of folic acid metabolites in host-virus interactions. This research paves the way for novel therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating the molecular mechanisms underlying the protective effects of folic acid in the context of viral infections.
Assuntos
COVID-19 , Ácido Fólico , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2 , Ácido Fólico/análogos & derivados , Ácido Fólico/metabolismo , Ácido Fólico/farmacologia , Simulação de Dinâmica Molecular , Ligação Proteica , Análise Espectral RamanRESUMO
Dihydrofolate reductase (DHFR) is an essential enzyme for nucleotide metabolism used to obtain energy and structural nucleic acids. Schistosoma mansoni has all the pathways for pyrimidine biosynthesis, which include the thymidylate cycle and, consequentially, the DHFR enzyme. Here, we describe the characterization of Schistosoma mansoni DHFR (SmDHFR) using isothermal titration calorimetry for the enzymatic activity and thermodynamic determination, also the folate analogs inhibition. Moreover, X-ray crystallography was used to determine the enzyme atomic model at 1.95 Å.
Assuntos
Schistosoma mansoni/enzimologia , Tetra-Hidrofolato Desidrogenase/metabolismo , Animais , Calorimetria , Cristalografia por Raios X , Ensaios Enzimáticos , Ácido Fólico/análogos & derivados , Congelamento , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Síncrotrons , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/isolamento & purificaçãoRESUMO
Tuberculosis is a disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious pathogen, with a high prevalence in developing countries in Africa and Asia. There still is a need for the development or repurposing of novel therapies to combat this disease owing to the long-term nature of current therapies and because of the number of reported resistant strains. Here, structures of dihydrofolate reductase from M. tuberculosis (MtDHFR), which is a key target of the folate pathway, are reported in complex with four antifolates, pyrimethamine, cycloguanil, diaverdine and pemetrexed, and its substrate dihydrofolate in order to understand their binding modes. The structures of all of these complexes were obtained in the closed-conformation state of the enzyme and a fine structural analysis indicated motion in key regions of the substrate-binding site and different binding modes of the ligands. In addition, the affinities, through Kd measurement, of diaverdine and methotrexate have been determined; MtDHFR has a lower affinity (highest Kd) for diaverdine than pyrimethamine and trimethoprim, and a very high affinity for methotrexate, as expected. The structural comparisons and analysis described in this work provide new information about the plasticity of MtDHFR and the binding effects of different antifolates.
Assuntos
Antagonistas do Ácido Fólico/química , Ácido Fólico/análogos & derivados , Mycobacterium tuberculosis/enzimologia , Tetra-Hidrofolato Desidrogenase/química , Sítios de Ligação , Cristalização/métodos , Cristalografia por Raios X/métodos , Escherichia coli/genética , Ácido Fólico/química , Humanos , Ligantes , Modelos Moleculares , Conformação Proteica , Tuberculose/microbiologiaRESUMO
Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration.
Assuntos
Materiais Biocompatíveis/uso terapêutico , Fenda Labial/terapia , Fissura Palatina/terapia , Medicina Regenerativa/métodos , Animais , Fenda Labial/epidemiologia , Fenda Labial/patologia , Fenda Labial/fisiopatologia , Fissura Palatina/epidemiologia , Fissura Palatina/patologia , Fissura Palatina/fisiopatologia , Ácido Fólico/análogos & derivados , Ácido Fólico/uso terapêutico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Osteogênese/efeitos dos fármacos , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodosRESUMO
Resumo OBJETIVO Compreender as percepções das gestantes acerca do cuidado recebido durante o pré-natal, no âmbito da atenção primária à saúde. MÉTODO Estudo qualitativo, baseado na Grounded Theory. A coleta de dados foi realizada de agosto a dezembro de 2016, através de entrevista semiestruturada com 12 gestantes que realizaram acompanhamento pré-natal na atenção primária do município de Florianópolis/SC/Brasil. A coleta e análise dos dados foram realizadas concomitantemente. Na análise de dados utilizou-se a codificação aberta e axial. RESULTADOS Foram elaboradas três categorias, sendo elas: O cuidado antes e durante a gestação. Participação em grupos de gestantes e, Cuidado de qualidade durante a gestação. CONCLUSÃO As percepções das gestantes acerca do cuidado recebido durante o pré-natal estão relacionadas à atenção dispensada, ao acolhimento humanizado, consideração da subjetividade da gestante e amparo nos momentos difíceis que tornam este período satisfatório.
Resumen OBJETIVO Comprender las percepciones de las gestantes acerca del cuidado recibido durante el prenatal, en el ámbito de la atención primaria a la salud. MÉTODO Estudio cualitativo, basado en la Grounded Theory. La recolección de datos fue realizada de agosto a diciembre de 2016, a través de entrevista semiestructurada con 12 gestantes en la atención primaria a la salud del municipio de Florianópolis/SC/Brasil. La recolección y análisis de los datos se realizaron concomitantemente. En el análisis de datos se utilizó la codificación abierta y axial. RESULTADOS Fueron elaboradas tres categorías, siendo ellas: El cuidado antes y durante la gestación, Participación en grupos de gestantes y, Cuidado de calidad durante la gestación. CONCLUSIÓN Las percepciones de las gestantes acerca del cuidado recibido durante el prenatal están relacionadas la atención dispensada, acogida humanizada, consideración de la subjetividad de la gestante y amparo en los momentos difíciles que hacen este período satisfactorio.
Abstract OBJECTIVE To understand the perceptions of pregnant women about the care received during prenatal care, in the field of primary health care. METHOD Qualitative study, based on Grounded Theory. Data collection was performed from August to December 2016, through a semi-structured interview with 12 pregnant women who received prenatal care in the city of Florianópolis/SC/Brazil. Data collection and analysis were performed concomitantly. Data analysis was performed using open and axial coding. RESULTS Three categories were elaborated: Care before and during gestation, Participation in groups of pregnant women, and Quality care during pregnancy. CONCLUSION The perceptions of the pregnant women about the care received during the prenatal care is related to the care given, humanized reception, consideration of the pregnant woman's subjectivity and support in the difficult moments that make this period satisfactory.
Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Adulto Jovem , Cuidado Pré-Natal/normas , Atenção Primária à Saúde/normas , Qualidade da Assistência à Saúde , Cuidado Pré-Natal/psicologia , Complexo Vitamínico B/administração & dosagem , Brasil , Compostos Ferrosos/administração & dosagem , Pesquisa Qualitativa , Gestantes/psicologia , Gravidez não Planejada , Ácido Fólico/administração & dosagem , Ácido Fólico/análogos & derivadosRESUMO
Size, shape, and surface properties of superparamagnetic iron oxide nanoparticles (SPIONs) can influence their interaction with biological systems, particularly the incorporation by tumor cells and consequently the biological activity and efficiency in biomedical applications. Several strategies have been used to evaluate cellular uptake of SPIONs. While qualitative methods are generally based on microscopy techniques, quantitative assays are carried out by techniques such as inductively coupled plasma-mass spectrometry and flow cytometry. However, inexpensive colorimetric methods based on equipments commonly found in chemistry and biochemistry laboratories are preferred for routine measurements. Nevertheless, colorimetric assays must be used judiciously, particularly when nanoparticles are involved, since their interaction with biological constituents tends to lead to quite underestimated results. Thus, herein described is a colorimetric protocol using 2,2'-bipyridine as chromogenic ligand, where each step was optimized and validated by total reflection X-ray fluorescence spectroscopy, realizing a highly reproducible and reliable method for determination of iron content in cells incubated with SPIONs. The limit of blank and limit of detection were determined to be as low as 0.076 and 0.143 µg Fe/mL, using sample volumes as small as 190 µL and a number of cells as low as 2.0 × 105. Furthermore, three different types of surface-functionalized nanoparticles were incorporated in cells and evaluated through this protocol, enabling to monitor the additive effect of o-phosphorylethanolamine (PEA) and folic acid (FA) conjugation on iron oxide nanoparticles (SPION-PEA and SPION-PEA/FA), that enhanced the uptake by HeLa cells, respectively, by four and ten times when compared to SPIONs conjugated with nonbioactive molecules. Graphical abstract Colorimetric determination of superparamagnetic iron oxide nanoparticles (SPIONs) incorporated by cells.
Assuntos
Meios de Contraste/análise , Etanolaminas/análise , Ácido Fólico/análise , Nanopartículas de Magnetita/análise , Permeabilidade da Membrana Celular , Sobrevivência Celular , Colorimetria/métodos , Meios de Contraste/química , Meios de Contraste/farmacocinética , Etanolaminas/química , Etanolaminas/farmacocinética , Compostos Férricos/análise , Compostos Férricos/química , Compostos Férricos/farmacocinética , Ácido Fólico/análogos & derivados , Ácido Fólico/farmacocinética , Células HeLa , Humanos , Nanopartículas de Magnetita/químicaRESUMO
We evaluated the addition of folic acid to the extender TRIS-egg yolk used in cryopreservation, seekingimprovements for the sperm kinetics and mitochondrial activity post-thawing. Were evaluated sevenejaculates/animal from six Santa Inês by Artificial Vagina, with minimum values of motility by 70.0% and vigor3. We evaluated the seminal pool for concentration and morphology. We diluted in Tris-egg yolk extender forcryopreservation, dividing it in control, Group 2 we added 10.000 uM and Group 3 we added 5000 uM of folicacid. We froze in straws(0.25 mL). Was evaluated for motility and vigor, post-thawing by slow term-resistancetest, the times T0, T60, T120 and T180 minutes one week after. For the mitochondrial activity evaluation, wasused cationic lipophilic fluorochrome JC-1. The folic acid effects were analyzed using ANOVA followed byStudent Newman-Keuls test. The groups with folic acid showed significant higher motility. Mitochondrialactivity did not differ between groups.(AU)
Assuntos
Animais , Masculino , Criopreservação/métodos , Criopreservação/veterinária , Ovinos/embriologia , Ácido Fólico/análogos & derivados , Ácido Fólico/análise , Antioxidantes/análiseRESUMO
We evaluated the addition of folic acid to the extender TRIS-egg yolk used in cryopreservation, seekingimprovements for the sperm kinetics and mitochondrial activity post-thawing. Were evaluated sevenejaculates/animal from six Santa Inês by Artificial Vagina, with minimum values of motility by 70.0% and vigor3. We evaluated the seminal pool for concentration and morphology. We diluted in Tris-egg yolk extender forcryopreservation, dividing it in control, Group 2 we added 10.000 uM and Group 3 we added 5000 uM of folicacid. We froze in straws(0.25 mL). Was evaluated for motility and vigor, post-thawing by slow term-resistancetest, the times T0, T60, T120 and T180 minutes one week after. For the mitochondrial activity evaluation, wasused cationic lipophilic fluorochrome JC-1. The folic acid effects were analyzed using ANOVA followed byStudent Newman-Keuls test. The groups with folic acid showed significant higher motility. Mitochondrialactivity did not differ between groups.
Assuntos
Masculino , Animais , Antioxidantes/análise , Criopreservação/métodos , Criopreservação/veterinária , Ovinos/embriologia , Ácido Fólico/análise , Ácido Fólico/análogos & derivadosRESUMO
The selective action of drugs in tumor cells is a major problem in cancer therapy. Most chemotherapy drugs act nonspecifically and damage both cancer and healthy cells causing various side effects. In this study, the preparation of a selective drug delivery system, which is able to act as a carrier for hydrophobic and anticancer drugs is reported. Amino-functionalized silica nanoparticles loaded with curcumin were successfully synthesized via sol-gel approach and duly characterized. Thereafter, the targeting ligand, folate, was covalently attached to amino groups of nanoparticle surface through amide bond formation. The cytotoxic effect of nanoparticles on prostate cancer cells line was evaluated and compared to normal cells line (prostate epithelial cell). Cytotoxicity experiments demonstrated that folate-functionalized nanoparticles were significantly cytotoxic to tumor cells, whereas normal cells were much less affected by the presence of these structures.
Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Portadores de Fármacos/síntese química , Nanopartículas/química , Dióxido de Silício/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Curcumina/toxicidade , Dimetil Sulfóxido , Portadores de Fármacos/toxicidade , Ácido Fólico/análogos & derivados , Ácido Fólico/química , Ácido Fólico/toxicidade , Humanos , Nanopartículas/toxicidade , Tamanho da Partícula , Propilaminas/química , Propilaminas/toxicidade , Dióxido de Silício/síntese química , Dióxido de Silício/toxicidadeRESUMO
The objective of this study was to evaluate the estrogenic effects and mechanisms of three flavonoid components in Xiaoyao powder: quercetin, kaempferol, and isorhamnetin. The drugs were used to treat estrogen receptor (ER)-positive human breast cancer MCF-7 cells, and proliferation was measured using the MTT method. The expression of proteins and mRNA of the ER subtype were measured using western blotting and real time polymerase chain reaction. The quercetin (10(-2) µM, 10(-3) µM), kaempferol (100 µM, 10(-2) µM), and isorhamnetin (10(-3) µM) promoted the proliferation of MCF-7 cells, and the expression of ERα and ERß proteins and mRNA were all increased significantly (P < 0.05). These effects were reversed by treatment with 0.1 µM estrogen antagonist ICI182780. Three flavonoid components in Xiaoyao powder increased the expression of proteins and mRNA of ERα and ERß and promoted the proliferation of MCF-7 cells. These estrogenic effects were mediated by the ER.
Assuntos
Medicamentos de Ervas Chinesas/química , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Quempferóis/farmacologia , Quercetina/análogos & derivados , Quercetina/farmacologia , RNA Mensageiro/genética , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/agonistas , Receptor beta de Estrogênio/metabolismo , Ácido Fólico/análogos & derivados , Ácido Fólico/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Quempferóis/antagonistas & inibidores , Células MCF-7 , Pós/química , Quercetina/antagonistas & inibidores , RNA Mensageiro/agonistas , RNA Mensageiro/metabolismo , Transdução de SinaisRESUMO
In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹59Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Ehrlich/radioterapia , Sistemas de Liberação de Medicamentos , Ácido Fólico/análogos & derivados , Gadolínio DTPA/administração & dosagem , Polietilenoglicóis/química , Compostos Radiofarmacêuticos/administração & dosagem , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Ehrlich/patologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Sistemas de Liberação de Medicamentos/efeitos adversos , Feminino , Ácido Fólico/química , Gadolínio , Gadolínio DTPA/efeitos adversos , Gadolínio DTPA/uso terapêutico , Concentração de Íons de Hidrogênio , Dose Letal Mediana , Lipossomos , Fígado/patologia , Fígado/fisiopatologia , Fígado/efeitos da radiação , Camundongos , Necrose , Radioisótopos , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico , Propriedades de Superfície , Carga Tumoral/efeitos da radiação , Aumento de Peso/efeitos da radiaçãoRESUMO
Thymidylate synthase (TS) catalyzes the synthesis of deoxythymidine monophosphate (dTMP), which is an essential precursor for DNA synthesis. The rationale underlying drug design is to identify compounds that differentially inhibit a viral or parasite enzyme vs. the host homologue. We studied the TS of the white spot syndrome virus (WSSV TS) and the corresponding TS from the host, the marine invertebrate shrimp Litopenaeus vannamei. TS is the only de novo source of dTMP and is essential for host and viral DNA replication. To establish proof of principle, we cloned a full-length TS cDNA from the white shrimp L. vannamei (shrimp TS) that corresponds to a deduced sequence of 289 amino acids and over-expressed it to study inhibition of both shrimp and viral TSs. Steady-state kinetic parameters for both TSs are similar, and dissociation (K(d)) or half maximal inhibitory concentration constants (IC(50)) did not show differential inhibition between the folate analogues. Differences in their amino acid sequence are not reflected in theoretical molecular models of both TSs, since both appear to have identical active sites. These results suggest that the eukaryotic TS active site is very constrained into the functional residues involved in reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP).
Assuntos
Penaeidae/enzimologia , Timidilato Sintase/metabolismo , Vírus da Síndrome da Mancha Branca 1/enzimologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Domínio Catalítico/genética , Clonagem Molecular , Nucleotídeos de Desoxiuracil/metabolismo , Ácido Fólico/análogos & derivados , Ácido Fólico/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Isoindóis/farmacologia , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Quinazolinas/farmacologia , Alinhamento de Sequência , Timidilato Sintase/antagonistas & inibidores , Timidilato Sintase/genéticaRESUMO
In this report, we have reanalyzed genotyping data in a collection of families from South America based on maternal origin. Genotyping analysis was performed at the Craniofacial Anomalies Research Center at the University of Iowa. These genotypes were derived from genomic DNA samples obtained from blood spots from children born with isolated orofacial clefts in 45 hospitals located in eight countries (Argentina, Bolivia, Brazil, Chile, Ecuador, Paraguay, Uruguay, and Venezuela) collaborating with ECLAMC (Latin American Collaborative Studies of Congenital Malformations) between January 1998 and December 1999. Dried blood samples were sent by regular mail to the Laboratory of Congenital Malformations, Federal University of Rio de Janeiro. Previous findings suggested that mitochondrial haplotype D is more commonly found among cleft cases born in South America. We hypothesized that association of certain genes may depend upon the ethnic origin, as defined by population-specific markers. Therefore, we tested if markers in MTHFR (5,10-methylenetetrahydrofolate reductase) and RFC1 (reduced folate carrier 1) were associated with oral clefts, depending on the maternal origin defined by the mitochondrial haplotype. Transmission distortion of alleles in MTHFR C677T and RFC1 G80A polymorphic variants was tested in 200 mother/affected child pairs taking into consideration maternal origin. RFC1 variation was over-transmitted to children born with cleft lip only (P = 0.017) carrying mitochondrial DNA haplotypes other than haplotype D. Our results provide a new indication that variation in RFC1 may contribute to cleft lip only. Future studies should investigate the association between oral clefts and RFC1 based on more discrete phenotypes.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Ácido Fólico/análogos & derivados , Proteínas de Membrana Transportadoras/genética , População Negra , Fenda Labial/etnologia , Fissura Palatina/etnologia , DNA Mitocondrial/genética , Feminino , Ácido Fólico/genética , Marcadores Genéticos , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Indígenas Sul-Americanos , Recém-Nascido , Polimorfismo Genético , Proteína Carregadora de Folato Reduzido , América do Sul , População BrancaRESUMO
In this report, we have reanalyzed genotyping data in a collection of families from South America based on maternal origin. Genotyping analysis was performed at the Craniofacial Anomalies Research Center at the University of Iowa. These genotypes were derived from genomic DNA samples obtained from blood spots from children born with isolated orofacial clefts in 45 hospitals located in eight countries (Argentina, Bolivia, Brazil, Chile, Ecuador, Paraguay, Uruguay, and Venezuela) collaborating with ECLAMC (Latin American Collaborative Studies of Congenital Malformations) between January 1998 and December 1999. Dried blood samples were sent by regular mail to the Laboratory of Congenital Malformations, Federal University of Rio de Janeiro. Previous findings suggested that mitochondrial haplotype D is more commonly found among cleft cases born in South America. We hypothesized that association of certain genes may depend upon the ethnic origin, as defined by population-specific markers. Therefore, we tested if markers in MTHFR (5,10-methylenetetrahydrofolate reductase) and RFC1 (reduced folate carrier 1) were associated with oral clefts, depending on the maternal origin defined by the mitochondrial haplotype. Transmission distortion of alleles in MTHFR C677T and RFC1 G80A polymorphic variants was tested in 200 mother/affected child pairs taking into consideration maternal origin. RFC1 variation was over-transmitted to children born with cleft lip only (P = 0.017) carrying mitochondrial DNA haplotypes other than haplotype D. Our results provide a new indication that variation in RFC1 may contribute to cleft lip only. Future studies should investigate the association between oral clefts and RFC1 based on more discrete phenotypes.
Assuntos
Feminino , Humanos , Recém-Nascido , Fenda Labial/genética , Fissura Palatina/genética , Ácido Fólico/análogos & derivados , Proteínas de Membrana Transportadoras/genética , População Negra , Fenda Labial/etnologia , Fissura Palatina/etnologia , DNA Mitocondrial/genética , População Branca , Ácido Fólico/genética , Marcadores Genéticos , Predisposição Genética para Doença/genética , Haplótipos , Indígenas Sul-Americanos , Polimorfismo Genético , América do SulRESUMO
Oxidation of LDL contributes to endothelial dysfunction and atherosclerosis. This process could be associated with hyperhomocysteinemia, a condition that can be reduced after folic acid treatment. Because a reduction in LDL oxidation may improve endothelial function, we studied the effect of some vitamins (folic acid, 5-methyltetrahydrofolic acid, and vitamin B-12) on LDL oxidation, either in the presence or absence of homocysteine. For this purpose, two in vitro systems were used: an endothelial cell-catalyzed LDL oxidation system and a cell-free copper-initiated LDL oxidation system. The kinetics of copper-catalyzed LDL oxidation was determined by continuous monitoring of the production of conjugated dienes in the reaction medium. TBARS production, a parameter of lipid peroxidation, was also evaluated. In both in vitro systems, only 5-methyltetrahydrofolic acid was able to decrease TBARS production in a concentration-dependent manner, independently of the presence or absence of homocysteine. In the copper-induced LDL oxidation system, vitamin B-12 and 5-methyltetrahydrofolic acid increased the lag time of conjugated diene production by 25 and 47%, respectively, suggesting that both vitamins in this system had antioxidant properties. Folic acid was unable to show antioxidant properties when included in either in vitro system. The results demonstrate that 5-methyltetrahydrofolic acid and vitamin B-12 are important protective agents against LDL oxidative modifications.
Assuntos
Cobre/farmacologia , Endotélio Vascular/fisiologia , Ácido Fólico/farmacologia , Homocisteína/farmacologia , Lipoproteínas LDL/sangue , Vitamina B 12/farmacologia , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Ácido Fólico/análogos & derivados , Humanos , Cinética , Lipoproteínas LDL/efeitos dos fármacos , Valores de Referência , Veias UmbilicaisRESUMO
Se realizó una revisión bibliográfica actualizada acerca de las tendencias actuales en el tratamiento del embarazo ectópico. Se describen los diferentes métodos de tratamientos médicos, quirúrgicos, conservadores y radicales así como el uso de la cirugía laparoscópica
Assuntos
Humanos , Adulto , Feminino , Gravidez , Ácido Fólico/análogos & derivados , Gravidez Ectópica/cirurgia , Gravidez Ectópica/tratamento farmacológico , Leucovorina , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
The serum/plasma total homocysteine (tHcy) concentration, now recognized as an independent risk factor for accelerated atherosclerotic disease, is increased in overtly hypothyroid patients, and it decreases with thyroid replacement therapy. Whether or not individuals with subclinical hypothyroidism also increase their tHcy concentrations, and whether this elevation might help to explain the increased prevalence of the atherosclerotic diseases observed in this condition, remains unclear. If individuals with subclinical hypothyroidism have higher tHcy concentrations than euthyroid subjects, there would be added incentive to treat this condition earlier. In this cross-sectional study (New Mexico Elder Health Survey) of a randomly selected sample of Medicare recipients (age > or =65 years), no significant difference in serum tHcy concentrations could be detected between the 112 participants with subclinical hypothyroidism (Groups 2 and 3) and the 643 participants with thyrotropin (TSH) values < or =4.6 microU/mL (Group 1) after adjusting for differences in gender, ethnicity, age, and serum concentrations of folate, vitamin B(12), and creatinine. Only those participants with the highest TSH levels (>10 microU/mL) (Group 3) had a significantly higher prevalence of coronary heart disease (CHD) when compared against Group 1 participants (p = 0.007). No consistent significant differences in the prevalences of CHD or in the CHD risk factors examined were observed when all participants with subclinical hypothyroidism (Groups 2 and 3 combined) were compared against Group 1 participants.