ABSTRACT
Guanine-rich sequences may fold into highly ordered structures known as G-quadruplexes. Apart from the monomeric G-quadruplex, these sequences may form multimeric structures that are not usually considered when studying interaction with ligands. This work studies the interaction of a ligand, crystal violet, with three guanine-rich DNA sequences with the capacity to form multimeric structures. These sequences correspond to short stretches found near the promoter regions of c-kit and SMARCA4 genes. Instrumental techniques (circular dichroism, molecular fluorescence, size-exclusion chromatography and electrospray ionization mass spectrometry) and multivariate data analysis were used for this purpose. The polymorphism of G-quadruplexes was characterized prior to the interaction studies. The ligand was shown to interact preferentially with the monomeric G-quadruplex; the binding stoichiometry was 1:1 and the binding constant was in the order of 105M-1 for all three sequences. The results highlight the importance of DNA treatment prior to interaction studies.
Subject(s)
DNA , G-Quadruplexes , Polymorphism, Genetic , Chromatography, Gel , Circular Dichroism , DNA/chemistry , DNA/metabolism , Gentian Violet/chemistry , Gentian Violet/metabolism , Guanine/chemistry , Guanine/metabolism , Ligands , Multivariate Analysis , Nucleic Acid Denaturation , Spectrometry, Mass, Electrospray IonizationABSTRACT
A new form of clinical treatment is proposed for dystonias and torticollis using flunitrazepam (FN), a powerful agonist of all benzodiazepine receptors of GABA neurons. FN has a specific effect in dystonic patients, specially those in which the hypnotic effect of this drug is absent or diminished, thus suggesting the existence of two different neurochemical categories of dystonias.
Subject(s)
Dystonia/drug therapy , Flunitrazepam/therapeutic use , Torticollis/drug therapy , Female , Humans , MaleABSTRACT
A new form of clinical treatment is proposed for dystonias and torticollis using flunitrazepam (FN), a powerful agonist of all benzodiazepine receptors of GABA neurons. FN has a specific effect in dystonic patients, specially those in which the hypnotic effect of this drug is absent or diminished, thus suggesting the existence of two different neurochemical categories of dystonias.
Subject(s)
Humans , Male , Female , Dystonia , Flunitrazepam , TorticollisABSTRACT
Two patients harboring invasive macroprolactinomas, on treatment with bromocriptine, developed cerebrospinal fluid rhinorrhea 16 and 17 months after the beginning of the medical therapy. Neither patient had previously been submitted to surgery or radiotherapy. The fistulae were surgically corrected. Cerebrospinal fluid leakage is a well-documented complication of pituitary tumors, mainly after surgery and/or radiotherapy, but the reports of its occurrence after primary treatment with bromocriptine are rare. Therefore, the possibility of this complication must be considered, especially in patients with invasive macroprolactinomas.