Development of potent tripodal G-quadruplex DNA binders and their efficient delivery to cancer cells by aptamer functionalised liposomes.

Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity. Moreover, the most potent G4 binders have been encapsulated in liposomes and AS1411 aptamer-targeted liposomes reaching nanomolar IC50 values for the most cytotoxic systems.

Incidence of injuries among professional football players in Spain during three consecutive seasons: A longitudinal, retrospective study.

OBJECTIVES: The aim of the study was to determine risk factors that maybe be associated with a higher incidence of injuries in elite football players in the Spanish league during a three-year follow-up. Injury was defined as a musculoskeletal complaint (pain and/or discomfort) reported by players to the medical staff and receiving medical attention. DESIGN: A longitudinal retrospective study. SETTING: and participants: Seventy-one players from Malaga Football Club, who were in the first squad team for three consecutive seasons. MAIN OUTCOME MEASURES: Incidence, location, severity of injuries were reported according to the Injury Consensus Group for football injuries. RESULTS: Three hundred and fifty six injuries were found, with the highest proportion (44%) being located in the thigh. We found 6.9 (SD 5.87) injuries per 1000 h of match time and 0.23 (SD 0.22) per 1000 h of training. Forwards presented the highest rates in both incidence and severity of injury. Exposure to training was inversely related to the total number of injuries, which means that the greater the exposure to training the lesser the number of injuries. CONCLUSIONS: This information can assist clinicians in the identification of risk factors and, thus, the elaboration of prevention programmes that reduce football injuries.

Biologics and Cardiovascular Disease.

The advent of biologic therapy has enhanced our ability to augment disease in an increasingly targeted manner. The use of biologics in cardiovascular disease (CVD) has steadily increased over the past several decades. Much of the early data on biologics and CVD were derived from their use in rheumatologic populations. Atherosclerosis, myocardial infarction, and heart failure have been closely linked to the inflammatory response. Accordingly, cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been targeted. Noninflammatory mediators, such as proprotein convertase subtilisin kexin type 9 (PCSK9), have been selected for therapeutic intervention as well. Furthermore, RNA interference (RNAi) therapy has emerged and may serve as another targeted therapeutic mechanism. Herein, we will review the history, obstacles, and advances in using biologic therapy for CVD.

Imaging atoms in medicine.

The innovations in science and technology have allowed researchers to look inside the human body. In some cases, like MRI, the protons present in the body generate enough signal for an image. However, the employ of certain atoms, metallic or non-metallic, enable detection through different imaging techniques (computed tomography, nuclear imaging, ultrasound or optical imaging), and improve the quality of the images. Here we discuss the different imaging atoms used depending on the imaging technique and the new possible imaging atoms for medical applications.

Litotripsia extracorpórea a 60 y 120 golpes por minuto: estudio prospectivo randomizado / Extracorporeal shock wave lithotripsy 60 versus 120 shocks per minute: results of a prospective randomized controlled trial

Diversa evidencia sugiere que las litotripsias a menor frecuencia son más eficientes en el tratamiento de las urolitiasis al aumentar la fragmentación en modelos experimentales y en algunas series clínicas. El objetivo de este trabajo es comparar la eficiencia del tratamiento con 60 respecto a 120 golpes por minuto (gpm) en un estudio prospectivo randomizado. Materiales y métodos: Pacientes con litiasis radioopaca, sin tratamiento previo, fueron prospectivamente sometidos a litotripsia a 60gpm (grupo 1) o 120 gpm (grupo 2), en forma randomizada. Se registró la ubicación (renal o ureteral) y tamaño (en mm) del cálculo. Se definió como éxito la ausencia del cálculo tratado al mes de seguimiento, controlado con radiografía simple. En el análisis estadístico se utilizó test chi cuadrado, con intervalo de confianza de 95 por ciento, considerando significativo p<0,05. Resultados: Se trataron 92 pacientes, de los cuales 46 recibieron litotripsia a 60 gpm y 46 a 120 gpm. Ambos grupos no presentan diferencias estadísticas en cuanto a la ubicación y tamaño del cálculo. El éxito global del tratamiento fue de 67,4 por ciento. El grupo 1 presentó mayor éxito (78 por ciento) que el grupo 2 (56 por ciento), siendo diferencias significativas (p=0,0008). En los cálculos renales, el grupo 1 tuvo un éxito de un 70,8 por ciento y el grupo 2 un 58,6 por ciento (p<0,05). En los cálculos ureterales, el grupo 1 tuvo un éxito de un 86,4 por ciento y el grupo 2 un 52,9 por ciento (p<0,05). El número de golpes promedio por litotripsia en el grupo 1 fue de 2326 y en el grupo 2 fue de 2842 (p<0,05). El tiempo requerido para realizar la litotripsia fue mayor en el grupo 1, sin diferencias significativas. Conclusiones: Las litotripsias a bajas frecuencias presentan una mayor efectividad en comparación con las realizadas a mayor frecuencia, requiriendo incluso un menor número de golpes para lograr una fragmentación exitosa, con una duración comparable.

Several experimental and clinical trials have shown that slow rate shock wave lithotripsy (SWL) improves stone fragmentation with a better outcome. The purpose of this trial is to compare the efficiency of slow versus fast rate SWL in a prospective randomized study. Materials and Methods: Previously untreated patients with radiopaque calculi were randomized to undergo treatment with SWL at 60 (group 1) or 120 (group 2) shocks per minute (spm). The location (renal uretheral) and size (mm) of the stone was registered. Treatment success was considered as stone-free patients at one month follow-up with simple x-ray’s. For statistical analysis we used the chi-square test. Results: 92 patients were treated, 46 patients with SWL at 60 spm and 46 at 120 spm. There were significant differences in location and size between both groups. Global treatment success was 67,4 percent. Group 1 had a success rate (78 percent) higher than group 2 (56 percent), that was stadistically significant. In renal stones, group 1 showed a higher success rate (70,8 percent) than group 2 (58,6 percent). In uretheral stones, group showed a higher success rate (86,4 percent) than group 2 (52,9 percent). Both renal and uretheral locations showed statistical difference (p<0,05). The average number of shock waves used in group 1 was 2326 and 2842 group 2 (p<0,05). The time required to complete the SWL was longer in group 1, without statistical difference. Conclusions: Slow rate SWL’s are more efficient than ones performed at fast rates, with a greater success in fragmentation of stones at a lower number of total shock waves, and with a similar treatment time.

Synthesis and characterisation of highly emissive and kinetically stable lanthanide complexes suitable for usage "in cellulo".

The synthesis and photophysical characterisation are reported of a series of cationic, neutral and anionic europium and terbium complexes based on structurally related, nonadentate ligands based on the cyclen macrocycle. Each complex incorporates a tetraazatriphenylene moiety and overall absolute emission quantum yields are in the range 15-40% in aerated aqueous media. Dynamic quenching of the lanthanide excited state occurs with electron-rich donors, e.g. iodide, ascorbate and urate, and a mechanistic interpretation is put forward involving an electron transfer process. The cationic lanthanide complexes are taken up by NlH/3T3 cells and tend to localise inside the cell nucleus.

Enantiopure lanthanide complexes incorporating a tetraazatriphenylene sensitiser and three naphthyl groups: exciton coupling, intramolecular energy transfer, efficient singlet oxygen formation and perturbation by DNA binding.

In cationic nine-coordinate chiral terbium and europium complexes incorporating exciton-coupled naphthyl groups and a tetraazatriphenylene sensitising chromophore, efficient intramolecular energy transfer occurs leading to population of the naphthyl triplet state. With the terbium complex, the absolute quantum yield of singlet oxygen formation is 51% (lambda(exc) 355 nm), and for the Eu complex the intensity of metal-based emission increases by up to 350% on binding to poly(dGdC) or calf-thymus DNA, and was greater for the delta-isomer.