Influence of pH and Mg(ii) on the catalytic core domain 5 of a bacterial group II intron.

RNA molecules fold into complex structures that allow them to perform specific functions. To compensate the relative lack of diversity of functional groups within nucleotides, metal ions work as crucial co-factors. In addition, shifted pKas are observed in RNA, enabling acid-base reactions at ambient pH. The central catalytic domain 5 (D5) hairpin of the Azotobacter vinelandii group II intron undergoes both metal ion binding and pH dependence, presumably playing an important functional role in the ribozyme's reaction. By NMR spectroscopy we have here characterized the metal ion binding sites and affinities for the hairpin's internal G-A mismatch, bulge, and pentaloop. The influence of Mg(ii) and pH on the local conformation of the catalytically crucial region is also explored by fluorescence spectroscopy.

Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one.

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe(3+), studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe(3+). The pFe(3+) value 22.0 of P1-iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al(3+), Cu(2+) and Zn(2+) has been studied to evaluate the possible use of P1 against a second toxic metal ion (Al(3+)), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelator.

Aplicación complementaria de terapia fotodinámica y de la radiación láser de Er:YAGal tratamiento no quirúrgico de la periodontitis crónica: estudio comparativo de sus efectos clínicos, antiinflamatorios y antimicrobianos / Adjunctive application of the photodynamic therapy and the Er:YAG laser radiation to non-surgical treatment of chronic periodontitis: comparative study of their clinical, anti-inflammatory and antimicrobial effects

Objetivos: Comparar efectos clínicos, antimicrobianos y antiinflamatorios de la terapia fotodinámica (TFD) y de la fototerapia con láser de Er:YAG aplicadas complementariamente al raspado y alisado radicular (RAR). Material y métodos: 45 pacientes con enfermedad periodontal crónica, fueron distribuidos aleatoriamente en 3 grupos de 15 para recibir: RAR, RAR complementado con terapia fotodinámica (RAR+TFD) o complementado con láser de Er:YAG (RAR+ERL). Se analizaron los parámetros clínicos: porcentaje de placa en boca total (PPBT), porcentaje de sangrado en boca total (PSBT) y profundidad de sondaje (PS), y se procedió a la recogida de fluido crevicular gingival (FCG) y de placa subgingival antes del tratamiento, a las 4 y 8 semanas posteriores. Se determinaron los niveles de Interleuquina 1β (IL-1β), Factor de Necrosis Tumoral α (FNT-α ) en FCG y su estado antioxidante total (EAT). Las muestras de flora subgingival fueron cultivadas para la determinación de 10 periodontopatógenos. Resultados y Discusión: No se encontraron diferencias estadísticamente significativas (DES) entre los tres tipos de tratamiento en cuanto a la evolución de los parámetros clínicos PPBT, PS, ni en cuanto al aumento de la capacidad antioxidante del FCG tras el tratamiento, ni tampoco en cuanto a la reducción de la flora subgingival total analizada, aunque sí se aprecia una ligera ralentización del proceso de recolonización bacteriana en el grupo RAR+Er:YAG. En cuanto al parámetro clínico PSBT, se observó un mayor descenso a las 8 semanas post-tratamiento en el grupo RAR+TFD, aunque no significativo. Sí se encontraron DES en cuanto a la evolución de los niveles de las citoquinas evaluadas: después del RAR los niveles de IL-1β y FNT-α se incrementaron y significativamente en el caso de FNT-α a las 8 semanas post-tratamiento. El procedimiento RAR+TFD mostró una tendencia a frenar dicho incremento y tras la aplicación de RAR+ERL dichos niveles descendieron, de forma más marcada en el caso de la IL-1β, durante el periodo de post-tratamiento evaluado (AU)

Aim: To compare clinical, microbiological and anti-inflammatory effects of the photodynamic therapy (PDT) and the Er:YAG laser phototherapy adjunctively applied to scaling and root planning (SRP). Material and Methods: Forty-five patients with chronic periodontitis were randomly assigned into 3 groups of 15 patients to receive: SRP, SRP followed by PDT (SRP+PDT) or SRP followed by Er:YAG laser phototherapy (SRP+ERL). Clinical parameters including full mouth plaque score (FMPS), full mouth bleeding score (FMBS) and probing pocket depth (PPD) were recorded and samples of gingival crevicular fluid (GCF) and subgingival plaque were taken at baseline, 4 and 8 weeks postoperatively. The GCF samples were analyzed for interleukin-1beta (IL-1β), tumour necrosis factor alpha (TNF-α ) and total antioxidative status (TAS). Subgingival plaque was analyzed by culture for 10 bacteria. Results and Discussion: No statistically significant differences were detected between the three kinds of treatment concerning the evolution of the clinical parameters FMPS and PPD, the increase of TAS in GCF and the subgingival plaque reduction, but the SRP+ERL treatment slightly slowed down the bacterial recolonization process. Concerning the clinical parameter FMBS, a slight decrease was observed 8 weeks post-therapy after SRP+PDT treatment. Statistically significant differences between groups were observed in the evolution of the levels of the cytokines evaluated: after SRP the levels of IL-1β and TNT-α increased, significatively in the case of TNT-α at 8 weeks post-therapy. The procedure SRP+PDT showed a trend to slow down this increase, and after the application of SRP+ERL these levels decreased, more severely in the case of IL-1β, during the whole post-therapy period (AU)

Treatment of gastric pyrosis with almagate in patients with and without endoscopically demonstrable duodenal ulcer. A multicentre clinical trial.

An open multicentre trial of a new clinical antacid, almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14(CO3)2 X 4H2O, Almax) has been made in 169 patients suffering from gastric pyrosis (heartburn). Clinical and endoscopical exploration revealed that 104 of the patients had an active duodenal ulcer and 60 of these (group II) were treated with antisecretory drugs (cimetidine or ranitidine) plus Almax and 44 (group III) with Almax alone. Endoscopic exploration in the remaining 65 patients (group I) failed to reveal the presence of an ulcer and they were also treated with Almax alone. In all groups Almax proved to be very effective and the majority of patients were symptom free by the end of the two week trial. 79.5% of the ulcer patients in group III required doses of 6-8 g/d whereas only 21.7% of those in group II with concomitant treatment with antisecretory drugs took more than 4 g/d. The nonulcer patients of group I also used lower doses and only 29.3% needed to reach 6-8 g/d. There was a significant increase in daily bowel movements in all groups which was considered to be advantageous by most patients. Overall tolerance was excellent and side effects (diarrhoea 7 cases, nauseas 5 cases and constipation 1 case) were few and transient and 84.2% of the patients expressed a clear preference for Almax over their previous antacid treatment.