Synthesis and in vitro behavior of β-TCP zirconia/polymeric biocomposites for bio-applications

Novel biocomposites were fabricated by impregnating β-tricalcium phosphate (β-TCP)/zirconia particles into the polymers matrix. The composite materials were characterized using thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), Fourier Transform Infrared (FT-IR) analyzes and Scanning Electron Microscopy (SEM). The results confirmed the conversion of hydroxyapatite (HA) to β-TCP at a sintering temperature of 1150 °C with or without zirconia powder. The in vitro behavior was assessed via measurement of calcium and phosphorus ions in SBF (simulated body fluid). FT-IR and SEM of the composites were performed pre and post immersion in SBF. The results prove that the bone like apatite layer formation was enhanced on the β-TCP-Z20/polymeric composite surface more than that on the β-TCP-Z10/polymeric composite. Therefore, the data confirmed that zirconia plays an important role in the enhancement of the apatite formation. The conclusions proved that the β-TCP-Z20/polymeric biocomposites, containing 20% of zirconia, are promising for bone remodeling applications.     

Sestrin 2 and AMPK Connect Hyperglycemia to Nox4-Dependent Endothelial Nitric Oxide Synthase Uncoupling and Matrix Protein Expression

Mesangial matrix accumulation is an early feature of glomerular pathology in diabetes. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. Here, we demonstrate that, in glomerular mesangial cells (MCs), endothelial nitric oxide synthase (eNOS) is uncoupled upon exposure to high glucose (HG), with enhanced generation of reactive oxygen species (ROS) and decreased production of nitric oxide. Peroxynitrite mediates the effects of HG on eNOS dysfunction. HG upregulates Nox4 protein, and inhibition of Nox4 abrogates the increase in ROS and peroxynitrite generation, as well as the eNOS uncoupling triggered by HG, demonstrating that Nox4 functions upstream from eNOS. Importantly, this pathway contributes to HG-induced MC fibronectin accumulation. Nox4-mediated eNOS dysfunction was confirmed in glomeruli of a rat model of type 1 diabetes. Sestrin 2-dependent AMP-activated protein kinase (AMPK) activation attenuates HG-induced MC fibronectin synthesis through blockade of Nox4-dependent ROS and peroxynitrite generation, with subsequent eNOS uncoupling. We also find that HG negatively regulates sestrin 2 and AMPK, thereby promoting Nox4-mediated eNOS dysfunction and increased fibronectin. These data identify a protective function for sestrin 2/AMPK and potential targets for intervention to prevent fibrotic injury in diabetes.     

Reversed-phase HPLC enantioseparation of pantoprazole using a teicoplanin aglycone stationary phase—Determination of the enantiomer elution order using HPLC-CD analyses

A direct HPLC method was developed for the enantioseparation of pantoprazole using macrocyclic glycopeptide-based chiral stationary phases, along with various methods to determine the elution order without isolation of the individual enantiomers. In the preliminary screening, four macrocyclic glycopeptide-based chiral stationary phases containing vancomycin (Chirobiotic V), ristocetin A (Chirobiotic R), teicoplanin (Chirobiotic T), and teicoplanin-aglycone (Chirobiotic TAG) were screened in polar organic and reversed-phase mode. Best results were achieved by using Chirobiotic TAG column and a methanol-water mixture as mobile phase. Further method optimization was performed using a face-centered central composite design to achieve the highest chiral resolution. Optimized parameters, offering baseline separation (resolution = 1.91 ± 0.03) were as follows: Chirobiotic TAG stationary phase, thermostated at 10°C, mobile phase consisting of methanol/20mM ammonium acetate 60:40 v/v, and 0.6 mL/min flow rate. Enantiomer elution order was determined using HPLC hyphenated with circular dichroism (CD) spectroscopy detection. The online CD signals of the separated pantoprazole enantiomers at selected wavelengths were compared with the structurally analogous esomeprazole enantiomer. For further verification, the inline rapid, multiscan CD signals were compared with the quantum chemically calculated CD spectra. Furthermore, docking calculations were used to investigate the enantiorecognition at molecular level. The molecular docking shows that the R-enantiomer binds stronger to the chiral selector than its antipode, which is in accordance with the determined elution order on the column—S- followed by the R-isomer. Thus, combined methods, HPLC-CD and theoretical calculations, are highly efficient in predicting the elution order of enantiomers.     

Redescription of a poorly known marine ciliate, Leptoamphisiella vermis Gruber, 1888 n. g., n. comb. (ciliophora, stichotrichia, pseudoamphisiellidae), from the Yellow Sea, China

Leptoamphisiella vermisGruber, 1888 n. g., n. comb. (basionym Epiclintes vermisGruber, 1888) is an extraordinarily large and worm-like marine stichotrichous ciliate. Based on a population isolated recently from coastal waters of Qingdao, China, the living morphology and infraciliature are redescribed and its taxonomic position is defined. Accordingly, a new diagnosis for this species is suggested: large, marine Leptoamphisiella with a conspicuous layer of pellicular alveoli; 400-1000 microm x 40-70 microm in vivo; body band-like, highly flexible; about 40 membranelles; always three frontal and two buccal cirri; 52-80 transverse cirri (TC) extending to the posterior end of the buccal field; 57-79 left midventral and 44-62 right midventral cirri; 62-102 cirri in left and 63-91 cirri in right marginal rows (MR); 9-13 dorsal kineties that extend the full body length; about 100 macronuclear nodules and 5-13 micronuclei. The diagnosis for the new genus is as follows: vermiform Pseudoamphisiellidae with strongly contractile body, differentiated frontal, buccal, and highly developed TC; two remarkably separated midventral rows; one MR on each side of the body; frontoterminal and caudal cirri absent. Leptoamphisiella vermis n. comb. is fixed as the type species of the new genus.     

Chromosome numbers in Brazilian species of Crotalaria (Leguminosae, Papilionoideae) and their taxonomic significance

Chromosome numbers were counted for 23 species of Crotalaria native to Brazil. Among these data there were new counts for 15 taxa, and some confirmed previous reports or represented numbers that were different from those cited previously. The chromosome numbers most frequently found were 2 n  = 16 and 2 n  = 32. Only C. incana L. had 2 n  = 14 and C. tweediana Benth. had 2 n  = 54. The counts 2 n  = 32 and 54 were found in species of section Calycinae and 2 n  = 16 and 14 in species of section Chrysocalycinae . The data revealed the importance of chromosomal parameters in the characterization of sections Calycinae and Chrysocalycinae in Brazil. We discuss the systematic significance and evolutionary aspects for the genus, comparing the results with the two sections that are native in Brazil.  © 2006 The Linnean Society of London, Botanical Journal of the Linnean Society , 2006, 151 , 271–277.     

Synthesis and bioevaluation of N-(arylalkyl)-homospermidine conjugates

N1-(Arylalkyl)homospermidines (1c-1f) and terminally piperazine-substituted homospermidine conjugates (2a-2e) were synthesized and evaluated for cytotoxicity in mouse leukemia L1210, alpha-difluoromethylornithine (DFMO)-treated L1210, melanoma B16, spermidine (SPD)-treated B16, and HeLa cell lines. Results demonstrated that homospermidine was a more effective vector than piperazine-substituted homospermidine in ferrying diverse arenes into cells via the polyamine transporter. The leading compound, 9-anthracenemethyl-homospermidine (1a), was shown to induce apoptosis in B16 cells and IL-3 dependent FL5.12A pro-B cells. The novel conjugate 4-biphenylmethyl-homospermidine (1e) could also induce apoptosis. However, it exhibited different effect on the cell cycle of B16 cells compared to 1a.     

An ecofriendly synthesis and DNA binding interaction study of some pyrazolo [1,5-a]pyrimidines derivatives

The DNA molecule is a target for plethora of anticancer and antiviral drugs that forms covalent and non-covalent adducts with major or minor groove of DNA. In present study we synthesized series of novel Pyrazolo [1,5-a]pyrimidine derivatives. The newly synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, and mass spectral data. The selected compounds were studied for interaction with Calf thymus DNA (CT-DNA) using electronic spectra, viscosity measurement and thermal denaturation studies. Further, molecular interactions were revealed for compound IIIa and IVa by computational methodologies. The preferred mode of ligand binding with double helical DNA as well as preferable DNA groove were explored by molecular docking in different DNA models.     

Radiation dose verification of an X-ray based blood irradiator using EBT3 radiochromic films calibrated using Gamma Knife machine

AimBlood irradiators (BI) initial acceptance testing and routine annual dosimetry checks require radiation dose measurements in order to comply with regulatory requirements.BackgroundTraditionally thermo-luminescence dosimeters (TLD) have been used to measure the dose. The EBT3 film is reported to be a better dosimeter for low energy X-rays than its predecessors EBT2 and EBT. To the best of our knowledge, the use of EBT3 films to perform dosimetry on X-ray based BI has not been reported yet.Materials and methodsWe performed routine radiation dosimetry checks using EBT3 films on a new X-ray based BI and compared the results with TLD dosimetry. Calibration films were irradiated with radiation beam from a Co-60 Gamma Knife (GK) radiosurgery machine and, alternatively, using an Ir-192 high dose rate (HDR) brachytherapy device. The films were calibrated to cover a wide dose range from 1 to 40 Gy. Such a wide dose range has not been reported yet in BI film dosimetry.ResultsWe obtained a relative difference of about 6.6% between doses measured using TLD and those measured using EBT3 films. Both irradiation methods using GK or HDR were found to be adequate for the calibration of the EBT3 Gafchromic films.ConclusionsWe recommend the use of EBT3 films in routine X-ray based BI dosimetry checks. The presented method takes advantage of available radiotherapy equipment that can be efficiently used for EBT3 films calibration. The method is fast, reproducible and saves valuable medical physicist's time.