ABSTRACT
The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.
Subject(s)
Oligonucleotides/therapeutic use , Spinal Muscular Atrophies of Childhood/drug therapy , Oligonucleotides, Antisense/therapeutic use , Oligonucleotides/administration & dosage , Brazil , Spinal Muscular Atrophies of Childhood/physiopathology , Ventilators, Mechanical , Randomized Controlled Trials as Topic , Oligonucleotides, Antisense/administration & dosage , Treatment Outcome , Clinical Trials, Phase III as Topic , Motor Skills/classificationABSTRACT
AS-ODNs, complementary to Schistosoma mansoni glucose transporter proteins (SGTP1 and SGTP4), were chosen as potential therapeutic agents for schistosomiasis. AS-SGTP1 oligos lowered the glucose uptake of adult worms both in vitro and ex vivo. The most effective AS-ODN was that of 21 nucleotides complementary to the SGTP1 nucleotide sequence, including the initiation region of mRNA translation. This oligo was found to decrease glucose uptake in vitro by as much as 50% and at a concentration of 4.0 mg/ml, it killed all male worms within 24 hours. A significant decrease, up to 34%, in glucose uptake was also noted when 100 mg/kg x2 (with a 2 hours interval) of AS-ODN was administered ex vivo. Two out of six anti-SGTP4 oligos also decreased the glucose uptake of adult worms in vitro by 25-44%. Added to the culture of schistosomula, two AS-SGTP4 oligos were found to decrease glucose uptake by 20-43%.
Subject(s)
Animals , Base Sequence , Blood Glucose/biosynthesis , Cell Cycle Proteins/drug effects , Female , Gene Targeting , Male , Molecular Sequence Data , Monosaccharide Transport Proteins/antagonists & inhibitors , Oligonucleotides, Antisense/administration & dosage , Schistosoma mansoni/geneticsABSTRACT
El advenimiento de las técnicas de DNA recombinante abrió una nueva era en los estudios genéticos. Por primera vez se hizo posible aislar, amplificar e incluso manipular segmentos de DNA de genes individuales. Estos métodos, junto con herramientas poderosas como los métodos de secuenciación, reacción en cadena de la polimerasa y el chips de DNA, han permitido el conocimiento de la estructura, función y regulación de los genes. Actualmente, las técnicas del DNA recombinante tienen muchas aplicaciones importantes, entre las que destacan la localización y clonación de genes responsables de enfermedades, lo que permite su diagnóstico molecular y la identificación precisa de individuos a través de sus huellas genómicas. Además, esta metodología ha permitido la producción comercial de genes y proteínas mediante ingeniería genética para su empleo en medicina y la creación de animales transgénicos