RESUMEN
PATIENTS AND METHODS: In this study, 13 patients (11 men and 2 women) undergoing hemodialysis (HD) with the use of a catheter placed into the inferior vena cava with percutaneous translumbar access were retrospectively evaluated. In the studied group, 16 procedures of percutaneous translumbar catheterization were performed. Complications connected with the presence of catheter, such as hematoma, thrombosis, infection, catheter movement or unsuccessful catheterization, were analyzed. Moreover, another aspect of our report was to evaluate the adequacy of HD treatment performed by lumbar catheter. RESULTS: The total time of translumbar catheter observation was 4,169 days. Average time of their functioning was 261 days. The most frequent reason for termination of the use of translumbar HD catheters was spontaneous/idiopathic removal - 2 cases. Episodes of infection and thrombosis per 1,000 days of catheter observation were 2.2 and 1.2, respectively. CONCLUSIONS: Based on our study, we can conclude that correctly performed percutaneous translumbar catheterization of the inferior vena cava, in order to produce a long-term vascular access for HD, is a valuable and safe method in patients after depletion of standard vascular accesses.
Asunto(s)
Cateterismo Venoso Central/métodos , Vértebras Lumbares , Diálisis Renal , Vena Cava Inferior , Adulto , Anciano , Puntos Anatómicos de Referencia , Obstrucción del Catéter/etiología , Infecciones Relacionadas con Catéteres/etiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Catéteres Venosos Centrales , Remoción de Dispositivos , Urgencias Médicas , Falla de Equipo , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Radiografía Intervencional , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Trombosis Venosa Profunda de la Extremidad Superior/etiología , Vena Cava Inferior/diagnóstico por imagenRESUMEN
RuII(arene) complexes have been shown to be promising anticancer agents, capable of overcoming major drawbacks of currently used chemotherapeutics. We have synthesized RuII(η6-arene) compounds carrying bioactive flavonol ligands with the aim to obtain multitargeted anticancer agents. To validate this concept, studies on the mode of action of the complexes were conducted which indicated that they form covalent bonds to DNA, have only minor impact on the cell cycle, but inhibit CDK2 and topoisomerase IIα in vitro. The cytotoxic activity was determined in human cancer cell lines, resulting in very low IC50 values as compared to other RuII(arene) complexes and showing a structure-activity relationship dependent on the substitution pattern of the flavonol ligand. Furthermore, the inhibition of cell growth correlates well with the topoisomerase inhibitory activity. Compared to the flavonol ligands, the RuII(η6-p-cymene) complexes are more potent antiproliferative agents, which can be explained by potential multitargeted properties.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Flavonoles/química , Compuestos de Rutenio/química , Compuestos de Rutenio/farmacología , Línea Celular Tumoral , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , ADN-Topoisomerasas de Tipo II/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-ActividadRESUMEN
A series of Cu(II), Co(II), Pt(II) and Zn(II) coordination compounds has been prepared by the reaction of the metal chlorides with pyrazine-2-carboxylic acid, pyridine-2-carboxylic acid, imidazole-4-carboxylic acid, benzimidazole-2-carboxylic acid and 1-methylimidazole-2-carboxylic acid. The complexes were characterized by IR, UV-VIS, elemental analysis, and some by (1) H-NMR, X-ray crystallography, HPLC and LC/MS spectroscopy. All complexes consist of a 2:1 ratio of ligand to metal ion. IR and X-ray crystallography show that coordination is through the nitrogen and carboxylate oxygen donor atoms of the ligand to form chelating rings. DFT calculations predict that the trans-coordinated isomers are thermodynamically more stable than their cis-forms. Only one of five complexes studied by X-ray crystallography, Cu(II) complex of 1-methylimidazole-2-carboxylic acid showed a cis-configured metal ion center. HPLC analysis indicated that Pt(II) complex of 1-methylimidazole-2-carboxylic acid is dominated (>90%) by the trans-configured complex. All other complexes showed one isomer, presumably the trans-form. The cytotoxic activity was investigated in human cancer cell lines in vitro; only the Pt(II) complexes were active. The antimicrobial activity against four bacterial strains and one fungi was estimated by the MIC method and best results were found amongst the Co(II) complexes. These results indicate that trans-coordinated bischelating N,O-heterocyclic carboxylates of Pt(II) are an interesting new class of potential antitumor agents.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/farmacología , Ácidos Heterocíclicos/síntesis química , Ácidos Heterocíclicos/química , Antiinfecciosos/química , Antineoplásicos/química , Ácidos Carboxílicos/química , Línea Celular Tumoral , Quelantes/química , Cobalto/química , Cobre/química , Humanos , Metales/química , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Compuestos Organometálicos/química , Platino (Metal)/química , Zinc/químicaRESUMEN
We have examined the biological activity of 12 platinum(II)-based DNA intercalators of the type [Pt(I(L))(A(L))](2+), where I(L) is an intercalating ligand (1,10-phenanthroline or a methylated derivative) and A(L) is an ancillary ligand (diaminocyclohexane, diphenylethylenediamine or 1,2-bis(4-fluorophenyl)-1,2-ethylenediamine). The chiral compounds (1-9) and the racemic compounds (10-12) were tested against a panel of human cancer cell lines, with a number of complexes displaying activity significantly greater than that of cisplatin (up to 100-fold increase in activity in the A-427 cell line). The activity of the complexes containing diphenylethylenediamine (8 and 9) and 1,2-bis(4-fluorophenyl)-1,2-ethylenediamine (10-12) was significantly lower compared to the complexes containing diaminocyclohexane (1-7). Further in vitro testing, such as DNA unwinding, competition assays, and DNase 1 footprinting, was conducted on the most active compound (5) and its enantiomer (6) to provide information about the mechanism of action. These complexes display activity in cisplatin resistant cell lines, have higher cellular uptake than cisplatin, and do not activate caspase-3 as cisplatin does, indicating that these complexes exhibit a different mechanism of action.