In vitro and in silico biological studies of novel thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives

In the present study, we report the synthesis, characterization of new series of thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives 3a–f and 4a–f. The newly synthesized compounds were screened for in vitro antimicrobial and antiviral activities. The probable mode of action of these active compounds was determined through in silico docking study by docking the receptor methionyl-tRNA synthetase and human inosine-5′-monophosphate dehydrogenase (IMPDH) for antibacterial and antiviral activities, respectively. Among the compounds, 4c exhibited excellent in vitro antimicrobial activity against all tested strains with binding and docking energies ?35.6 and ?12.4 kcal/mol, respectively. The antiviral studies were carried out for the selected compounds in which 4a exhibited 73.69 and 54.42 % of inhibition of buffalopox and camelpox viruses, respectively. Furthermore, compound 4a showed minimum docking and binding energy along with the maximum hydrogen/hydrophobic interaction with IMPDH. The study contributes towards identification and screening of potential antimicrobial and antiviral agent’s against the pathogens.     

Prospective randomized trial comparing shock wave lithotripsy and flexible ureterorenoscopy for lower pole stones smaller than 1 cm

In this study, we aimed to compare the success and complications of flexible ureterorenoscopy (F-URS) with its advanced technology and the accomplished method of shock wave lithotripsy (SWL) in the treatment of lower pole stones smaller than 1 cm. One hundred and forty patients were randomized as 70 undergoing SWL (Group 1) and 70 undergoing F-URS (Group 2). Patients were evaluated by plain X-ray and urinary ultrasound 1 week and after 3 months following SWL. The same procedure was done for F-URS patients 1 week after surgery and after 3 months. Success rates were established the day following the procedure and after 3 months. Fragmentation less than 3 mm was considered success. Mean operative time was 44 ± 7.4 min for Group 2 and mean fluoroscopy duration was 51 ± 12 s. In F-URS group, all the patients were stone free after 3 months (100 %). Group 1 had 2.7 ± 0.4 sessions of SWL. Sixty-four patients were stone free in that group after 3 months (91.5 %). The procedure yielded significant success in FURS group, even though patients underwent SWL for 2.7 ± 0.4 sessions and F-URS for 1 session (p < 0.05). With higher success and similar complication rates, fewer sessions per treatment, and advances in technology and experience, we believe F-URS has a potential to be the first treatment option over SWL in the future.     

Prophylactic administration of non‐organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone

Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC‐induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)‐approved substance for such pre‐treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad‐spectrum alternatives, we have assessed in vivo the mortality‐reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K‐27), when given in equitoxic dosage (25% of LD₀₁) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre‐treatment. All tested AChE inhibitors reduced terbufos sulfone‐induced mortality significantly (p ≤ 0.05) as compared with the non‐treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone‐induced mortality was achieved, when K‐27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre‐treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K‐27) in case of imminent OPC exposure may be a viable option. Copyright © 2013 John Wiley & Sons, Ltd.     

Transseptal use of high-density grid catheter for VT mapping and retrograde hemodynamic support with Impella pump in presence of Mitraclips

Journal of Interventional Cardiac Electrophysiology - We sought to establish the technical feasibility of VT-mapping with high-density catheters in patients with Mitraclips, requiring a hemodynamic...     

Unbiased spontaneous solar hydrogen production using stable TiO2–CuO composite nanofiber photocatalysts

We report on the optimization of electrospun TiO₂–CuO composite nanofibers as low-cost and stable photocatalysts for visible-light photocatalytic water splitting. The effect of different annealing atmospheres on the crystal structure of the fabricated nanofibers was investigated and correlated to the photocatalytic activity of the material. The presence of CuO resulted in narrowing the bandgap of TiO₂ and shifting the absorption edge into the visible region of the light spectrum. The effect of incorporating CuO within TiO₂ nanofibers on the crystal structure and composition was also investigated using X-ray diffraction (XRD), electron paramagnetic resonance (EPR), and X-ray photoelectron spectroscopy (XPS) techniques. The fabricated TiO₂–CuO composite nanofibers showed 117% enhancement in the amount of hydrogen evolved during the photocatalytic water splitting process compared to pure TiO₂. This enhancement was related to the created shallow defect states that facilitate charge transfer from TiO₂ to CuO and distinct characteristics of the composite nanofibers, such as the high surface area and directional charge transfer. The study showed that Cu is a promising alternative to noble metals as a catalyst in photocatalytic water splitting, with the advantage of being an Earth abundant element and a relatively cheap material.

We report on the optimization of electrospun TiO₂–CuO composite nanofibers as low-cost and stable photocatalysts for visible-light photocatalytic water splitting.     

Dentin Phosphophoryn-Derived Peptide Promotes Odontoblast Differentiation In Vitro and Dentin Regeneration In Vivo

The purpose of the present study was to investigate the effect of a peptide (i.e., SESDNNSSSRGDASYNSDES) derived from dentin phosphophoryn (DPP) with arginine-glycine-aspartic acid (RGD) motifs on odontoblast differentiation in vitro and to compare it with calcium hydroxide—a material used conventionally for vital pulp therapy—in terms of reparative dentin formation and pulp inflammation in vivo. Alkaline phosphatase activity assay and alizarin red S staining were performed to evaluate odontoblast-differentiation in cell culturing experiments. To observe the reparative dentin formation and pulp inflammation animal experiment was performed and examined by histological methods. The difference between the experimental group and the control group was analyzed statistically using a one-way ANOVA test. The results revealed that the DPP-derived RGD-containing peptide triggered odontoblast differentiation and mineralization in vitro. In rats undergoing direct pulp capping, the DPP-derived RGD-containing peptide was found to induce intensively formed reparative dentin with high compactness at week 4. On histological and morphometrical examinations, a smaller degree of pulpitis was observed in the specimens treated with the peptide than in those treated with calcium hydroxide. This study suggests that the DPP-derived RGD-containing peptide is a biocompatible, biodegradable and bioactive material for dentin regeneration.