Estudio de complejos metálicos con ligandos de interés biológico y/o farmacológico

El trabajo, que se inicia con una breve descripción de los métodos y técnicas utilizados, está dividido en tres partes. En la primera parte se encara el estudio de una serie de nuevos metalofármacos, varios de los cuales aparecen como potencialmente útiles para la suplementación de algunos bioelementos esenciales (Mg, Cu, Se, Zn) tanto en medicina humana como veterinaria. Asimismo, se presentan algunos complejos de litio adecuados para el tratamiento de desórdenes psíquicos y se estudia el comportamiento del complejo que forma el Zn(II) con la carnosina, un fármaco que está adquiriendo creciente interés y difusión. La segunda parte se dedica al estudio de algunos complejos de metales pesados, fundamentalmente de varios compuestos de plata con potencial actividad antimicrobiana, y de dos sacarinatos (de talio y de plomo), en el contexto de la utilización de este ligando en procesos de detoxificación. Finalmente, en la tercera parte, se estudian algunos complejos de los ácidos nicotínico y picolínico, en sistemas que guardan relación directa con el llamado factor de tolerancia a la glucosa. La Tesis se cierra con una serie de conclusiones generales en las que se presenta un breve resumen de los compuestos y sistemas estudiados y de los principales resultados obtenidos, concluyendo con el listado de los trabajos originales a que dieron lugar estos estudios.Tesis digitalizada en SEDICI gracias a la Biblioteca Central de la Facultad de Ciencias Exactas (UNLP).Facultad de Ciencias Exacta

Synthesis and characterization of EDTA complexes useful for trace elements supplementation

The synthesis of two heterobimetallic EDTA complexes, MgCu(EDTA).6H2O and ZnCu(EDTA).6H2O, is described. They were characterized by means of vibrational (infrared and Raman) and electronic (reflectance) spectroscopy. Several dissolution tests in 0.1 N HCl and simulated gastric juice were also performed. The results support the potential usefulness of these complexes for copper supplementation in human and veterinary medicine and to the simultaneous reinforcement of Mg(II) and Zn(II) levels.Facultad de Ciencias Exacta

Comparison of the effectiveness of kaolinitic clays with ordered and disordered structure for the removal of cd(ii)

La presencia de cadmio en el medioambiente se ha visto incrementada en el último siglo por factores antropogénicos. Los minerales arcillosos han demostrado su utilidad como adsorbentes, entre otras sustancias, de metales pesados; debido a su gran disponibilidad y el bajo costo del proceso. En este trabajo se evaluó la efectividad de dos arcillas de mediano porcentaje de mineral caolinítico disponibles en Argentina, una de estructura ordenada y la otra de estructura desordenada para remover Cd(II) de soluciones acuosas. Bajo las condiciones operadas (concentración inicial de Cd(II) 2-75 mg/L, 100 mL solución, 2 g/L de arcilla, 180 min de agitado, 22ºC) se concluyó que la caolinita desordenada posee mayor capacidad de adsorción a bajas concentraciones de Cd(II); mientras que la caolinita de estructura ordenada para altas concentraciones de Cd(II). Además, se observó que el proceso de adsorción puede estudiarse de manera efectiva mediante las isotermas de Freundlich y Langmuir.The presence of cadmiun in the environment has increased in the last century by anthropogenic factors. Clay minerals have proven to be useful as adsorbents of, among other substances, heavy metals; due to the high availability and low cost of the process. In this work, we evaluated the effectiveness of two clays with medium percentage of kaolinitic mineral available in Argentina, one with an ordered structure and the other with a disordered structure to remove Cd(II) from aqueous solutions. Under the operated conditions (initial concetration of Cd(II) 2-75 mg/L, 100 mL solution, 2 g/L of clay, 180 min of stirring, 22ºC) it was concluded that the disordered kaolinite has a greater adsorption capacity at low concentrations of Cd(II while orderly structure kaolinite for high Cd(II) concentrations. In addition, it was observed that the adsorption process can be effectively studied using the Freundlich and Langmuir isotherms.Fil: Portela, Gisele. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Tandil. Centro de Investigaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires. Sede Olavarria del Centro de Investifaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires | Universidad Nacional del Centro de la Pcia.de Bs.as.. Centro de Investigaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires. Sede Olavarria del Centro de Investifaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires.; ArgentinaFil: Tironi, Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Tandil. Centro de Investigaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires. Sede Olavarria del Centro de Investifaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires | Universidad Nacional del Centro de la Pcia.de Bs.as.. Centro de Investigaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires. Sede Olavarria del Centro de Investifaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires.; ArgentinaFil: Wagner, Claudia Cecilia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Tandil. Centro de Investigaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires. Sede Olavarria del Centro de Investifaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires | Universidad Nacional del Centro de la Pcia.de Bs.as.. Centro de Investigaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires. Sede Olavarria del Centro de Investifaciones En Fisica E Ingenieria del Centro de la Provincia de Buenos Aires.; Argentin

Synthesis and characterization of EDTA complexes useful for trace elements supplementation

The synthesis of two heterobimetallic EDTA complexes, MgCu(EDTA).6H2O and ZnCu(EDTA).6H2O, is described. They were characterized by means of vibrational (infrared and Raman) and electronic (reflectance) spectroscopy. Several dissolution tests in 0.1 N HCl and simulated gastric juice were also performed. The results support the potential usefulness of these complexes for copper supplementation in human and veterinary medicine and to the simultaneous reinforcement of Mg(II) and Zn(II) levels.Facultad de Ciencias Exacta

Experimental and Theoretical Studies of Calcium Fructoborate

Calcium fructoborate samples of composition Ca(C₆H₁₀O₆BO)₂·3.5H₂O were characterized by chemical analysis, infrared and Raman spectroscopy, and thermoanalytical (thermogravimetric and differential thermal analysis) data. Theoretical studies, using density functional theory, were made for seven different structural models of the fructoborate moiety, and the most stable structure could be derived from these calculations. The results of the theoretical study also allow improving the assignment of the vibrational spectra of the compound.Facultad de Ciencias ExactasCentro de Química Inorgánic

Spectroscopic and magnetic properties of a Ni(II) complex with citric acid

The complex compound K₂[Ni(cit)(H₂O)₂]₂·4H₂O (cit = triionized citrate ion) seems to be a good model for the investigation of Ni(II)/citrate interactions that are of interest in relation to nickel metabolism and bioaccumulation. Its infrared and Raman spectra were recorded and analyzed on the basis of its structural peculiarities. The magnetic susceptibility, investigated in the temperature range between 1.9 and 300 K, shows the absence of magnetic interactions between the two metal centers present in this structure.Centro de Química Inorgánic

Predicting the Proteins of Angomonas deanei, Strigomonas culicis and Their Respective Endosymbionts Reveals New Aspects of the Trypanosomatidae Family

Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. in an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei) and Strigomonas culicis (first known as Blastocrithidia culicis), respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. the monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. the monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. the assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine/pyrimidine metabolism. These findings increase our understanding of the intricate symbiotic relationship between the bacterium and the trypanosomatid host and provide clues to better understand eukaryotic cell evolution.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)ERC AdG SISYPHEUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Metab Macromol Firmino Torres de Castro, BR-21941 Rio de Janeiro, BrazilLab Bioinformat, Lab Nacl Computacao Cient, Rio de Janeiro, BrazilINRIA Grenoble Rhone Alpes, BAMBOO Team, Villeurbanne, FranceUniv Lyon 1, CNRS, UMR5558, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, FranceUniv Estadual Campinas, Inst Biol, Dept Genet Evolucao & Bioagentes, São Paulo, BrazilUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, São Paulo, BrazilLab Nacl Ciencia & Tecnol Bioetano, São Paulo, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, BrazilUniv Fed Goias, Inst Ciencias Biol, Mol Biol Lab, Goiania, Go, BrazilFundacao Oswaldo Cruz, Inst Carlos Chagas, Lab Biol Mol Tripanossomatideos, Curitiba, Parana, BrazilFundacao Oswaldo Cruz, Inst Carlos Chagas, Lab Genom Func, Curitiba, Parana, BrazilUniv Estadual Campinas, Ctr Pluridisciplinar Pesquisas Quim Biol & Agr, São Paulo, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Belo Horizonte, MG, BrazilUniv Fed Santa Catarina, Dept Microbiol Imunol & Parasitol, Ctr Ciencias Biol, Lab Protozool & Bioinformat, Florianopolis, SC, BrazilUniv Fed Vicosa, Dept Bioquim & Biol Mol, Ctr Ciencias Biol & Saude, Vicosa, MG, BrazilInst Butantan, Lab Especial Ciclo Celular, São Paulo, BrazilUniv São Paulo, Dept Biol, Fac Filosofia Ciencias & Letras Ribeirao Preto, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of Scienc

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases

Background: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Main body of the abstract: Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. Conclusion: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV