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20859921 | [Changes in the functional magnetic resonance imaging of the sensorimotor cortex in traumatic brain injury after intensive rehabilitation]. | To evaluate the potential reorganization of the sensorimotor cortex in a patient with traumatic brain injury after an intensive motor rehabilitation. |
20859920 | [Differential contribution of preoperatory studies to diagnosis in temporal lobe epilepsy surgery]. | It is necessary to know the degree of concordance of preoperative studies in temporal lobe epilepsy (TLE). AIM. To analyze the relative importance of different preoperative tests (vEEG, EEG, SPECT and MRI), the degree of agreement between them, and to develop a Bayesian probability model for diagnosis. |
20859922 | [Neuropsychological performance in cocaine addiction: a critical review]. | Chronic use of cocaine has been associated with a wide range of neuropsychological deficits affecting attention, memory, learning and executive functions. However, it has not been found a unique profile of impairment associated with cocaine addiction. |
20859923 | Sensorimotor integration: basic concepts, abnormalities related to movement disorders and sensorimotor training-induced cortical reorganization. | Sensorimotor integration is defined as the capability of the central nervous system to integrate different sources of stimuli, and parallelly, to transform such inputs in motor actions. |
20859924 | [Neurology in Byzantine medicine. An analysis of Alexander of Tralles' Medici libri duodecim]. | Byzantium continued Greek and Roman habit of pilation, and so, preserved medical knowledge. In addition, assimilating the influence of Monastic and Arabic medicine, Byzantine physicians transmitted original contributions including references to neurological diseases. Alexander of Tralles was one of major exponents of Byzantine medicine. He received his early medical training with his father, and in extensive travels, gathered medical knowledge and experience. |
20859928 | Semiochemicals of the common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), and their potential for use in monitoring and control. | The recent resurgence of mon bed bug, Cimex lectularius L., has driven an increase in research into the biology and behaviour of this pest. Current control is reliant on the application of insecticides, but, owing to the development of insecticide resistance, there is a need for new tools and techniques. Semiochemicals (behaviour- and physiology-modifying chemicals) could be exploited for management of bed bugs. The aim of this review was to evaluate studies undertaken in bed bug chemical ecology to date, with particular reference to how the research could be exploited for monitoring and control. Bed bugs, like many other insects, have plex olfactory system. Recent studies have characterised the olfactory sensilla, located on the terminal segment of the antennae, to functional classes by electrophysiological screening. Behavioural studies have revealed the presence of an alarm pheromone and potential airborne aggregation semiochemicals, but it is not yet understood if bed bugs use a sex pheromone during mating. Host location cues have been investigated, and carbon dioxide has been found to be highly attractive both in laboratory and in field studies. Recent field trials have tested blends of other potential kairomones, which have been shown to have an additive effect when used in a heated bed bug trap with carbon dioxide. The trap, bines heat and kairomones, is the only trap currently available with proven efficacy in the field. In order for semiochemicals to be useful for bed bug management, an increased knowledge and understanding of the biology, behaviour and chemical ecology of this insect is essential. |
20859929 | Differential scanning calorimetry thermal properties and oxidative stability indices of microwave heated extra virgin olive oils. | The use of differential scanning calorimetry (DSC) for assessing the deterioration effect of microwave heating on vegetable oils, and on olive oils in particular, has been partially explored in literature. The aim of this work was to evaluate the potential of DSC to discriminate among microwaved extra virgin olive oils (EvOo from different olive cultivar and origin), according to changes on thermal properties (upon cooling and heating) and traditional oxidative stability indices (peroxide, p-anisidine and TOTOX values). |
20859932 | Group psychoeducation for long-term offender patients with schizophrenia: an exploratory randomised controlled trial. | Psychoeducation is monly provided in forensic settings, but its effectiveness among long-term offender patients with schizophrenia has not yet been established in randomised controlled trials (RCTs). |
20859930 | Transient expression of antibodies in suspension plant cell suspension cultures is enhanced when co-transformed with the tomato bushy stunt virus p19 viral suppressor of gene silencing. | Two distinct transient expression approaches pared with assess the impact of the viral suppressor p19 on a binant protein production performed in Nicotiana benthamiana suspension culture. A parental N. benthamiana cell line was transiently transformed with either an Agrobacterium containing a gene construct for a murine IgG1 (R514) or concurrently with two Agrobacteria containing R514 or p19. In addition, a stably transformed N. benthamiana cell line that constitutively expresses p19 was transformed with R514-containing Agrobacterium. The parental N. benthamiana cell line that had been co-cultivated with both p19 and R514 achieved the highest yield of IgG1 (1.06 mg IgG1/kg FW; 0.024% pared with that obtained without p19 (0.61 mg IgG1/kg FW; 0.014% TSP). The N. benthamiana cell line that had been stably transformed with p19 only reached 0.25 mg IgG1/kg FW (0.009% TSP) when co-cultured with R514-containing Agrobacterium. Dual agroinfiltration of N. benthamiana leaves with p19 and R514 was also performed to assess for Agrobacteria efficiencies and 147.7 mg IgG1/kg FW were obtained. Therefore, our results demonstrate that transient co-transformation of plant cell suspension culture with two transformation vectors is feasible and that the use of the viral suppressor of silencing p19 significantly raises the production of the protein of interest. |
20859931 | Achieving high mass-throughput of therapeutic proteins through parvovirus retentive filters. | Parvovirus retentive filters that assure removal of viruses and virus-like particles during the production of therapeutic proteins significantly contribute to total manufacturing costs. Operational approaches that can increase throughput and reduce filtration area would result in a significant cost savings. bination of methods was used to achieve high throughputs of an antibody or therapeutic protein solution through three parvovirus retentive filters. These methods included evaluation of diatomaceous earth or size-based prefilters, the addition of additives, and the optimization of protein concentration, temperature, position, and solution pH. An optimum temperature of 35°C was found for maximizing throughput through the Virosart CPV and Viresolve Pro filters. Mass-throughput values of 7.3, 26.4, and 76.2 kg/m(2) were achieved through the Asahi Planova 20N, Virosart CPV, and Viresolve Pro filters, respectively, in 4 h of processing. Mass-throughput values of 73, 137, and 192 kg/m(2) were achieved through a Millipore Viresolve Pro filter in 4.0, 8.8, and 22.1 h of processing, respectively, during a single experiment. However, large-scale parvovirus filtration operations are typically controlled to limit volumetric throughput to below the level achieved during small-scale virus spiking experiments. The virus spike may cause significant filter plugging, limiting throughput. Therefore newer parvovirus filter spiking strategies should be adopted that may lead to more representative viral clearance data and higher utilization of large-scale filter capacity. |
20859934 | Experimental measurement of the regulation of anger and aggression in women with anorexia nervosa. | Anorexia nervosa (AN) is associated with difficulties in emotion regulation and this study aimed to examine emotion regulation experimentally in this pared to healthy controls (HCs). Sixty-six women took part: 22 with AN and 44 HCs. Both pleted the Rosenzweig Picture Frustration Study in which participants' responses to socially frustrating situations are scored regarding the direction of aggression/anger (outwardly/inwardly or neutralized) and type of aggression/anger (focused on the people or the obstacles in the situation, or solution-focused). Individuals with AN provided significantly fewer solution-focused responses and focused aggression on the people in the situation more often than HCs. There was also a trend for the AN group to neutralize aggression pared to HCs. The findings support models of AN which suggest that difficulties with emotional processing, particularly around anger are associated with AN. Future work could explore these initial findings in a larger sample. |
20859941 | Metal-assisted chemical etching of silicon: a review. | This article presents an overview of the essential aspects in the fabrication of silicon and some silicon/germanium nanostructures by metal-assisted chemical etching. First, the basic process and mechanism of metal-assisted chemical etching is introduced. Then, the various influences of the noble metal, the etchant, temperature, illumination, and intrinsic properties of the silicon substrate (e.g., orientation, doping type, doping level) are presented. The anisotropic and the isotropic etching behaviors of silicon under various conditions are presented. Template-based metal-assisted chemical etching methods are introduced, including templates based on nanosphere lithography, anodic aluminum oxide masks, interference lithography, and block-copolymer masks. The metal-assisted chemical etching of other semiconductors is also introduced. A brief introduction to the application of Si nanostructures obtained by metal-assisted chemical etching is given, demonstrating the promising potential applications of metal-assisted chemical etching. Finally, some open questions in the understanding of metal-assisted chemical etching piled. |
20859933 | Bionanoconjugate-based composites for decontamination of nerve agents. | We have developed posites that rapidly and effectively detoxify simulants of V- and G-type chemical warfare nerve agents. The approach was based on the efficient immobilization of organophosphorus hydrolase onto carbon nanotubes to form active and stable conjugates that were easily entrapped mercially available paints. The resulting posites showed no enzyme leaching and rendered >99% decontamination of 10 g/m(2) paraoxon, a simulant of the V-type nerve agent, in 30 minutes and >95% decontamination of diisopropylfluorophosphate, a simulant of G-type nerve agent, in 45 minutes. The formulations are expected to be environmentally friendly and to offer an easy to use, on demand, decontamination alternative to chemical approaches for sustainable material self-decontamination. |
20859948 | Ultrabright fluorescent mesoporous silica nanoparticles. | The first successful approach to synthesizing ultrabright fluorescent mesoporous silica nanoparticles is reported. Fluorescent dye is physically entrapped inside nanochannels of a silica matrix created during templated sol-gel self-assembly. The problem of dye leakage from open channels is solved by incorporation of hydrophobic groups in the silica matrix. This makes the patible with virtually any dye that can withstand the synthesis. The method is demonstrated using the dye Rhodamine 6G. The obtained 40-nm silica particles are about 30 times brighter than 30-nm coated water-soluble quantum dots. The particles are substantially more photostable than the encapsulated organic dye itself. |
20859952 | Dispersive liquid-liquid microextraction combined with nonaqueous capillary electrophoresis for the determination of fluoroquinolone antibiotics in waters. | Dispersive liquid-liquid microextraction (DLLME) bined for the first time with NACE-UV for the selective determination of eight fluoroquinolone antibiotics (lomefloxacin, levofloxacin, marbofloxacin, ciprofloxacin, sarafloxacin, enrofloxacin, danofloxacin and difloxacin) in mineral and run-off waters. Field-enhanced sample injection was carried out in order to improve the sensitivity, whereas pipemidic acid was used as internal standard. The BGE that plete separation of the eight analytes and the internal standard posed of 3 M acetic acid, 49 mM ammonium acetate in 55:45 v/v methanol:ACN. Optimum DLLME conditions (extraction of 5 mL of water at pH 7.6 with 685 μL of CHCl(3) and 1250 μL of ACN, extractant and disperser solvents, respectively) were achieved by means of experimental design methodology. Calibration curves of the whole method were obtained with correlation coefficients (R) higher than 0.994 in all cases. An accuracy and precision study was carried out at different levels of concentration, finding that there were no significant differences (Student's t-test) between real and spiked concentrations. |
20859951 | Alpha-1 antitrypsin variants in plasma from HIV-infected patients revealed by proteomic and glycoproteomic analysis. | Novel tools are necessary to explore proteins related to human immunodeficiency virus (HIV) infection. In this work, proteomic and glycoproteomic technology were employed to examine plasma samples from HIV-positive patients. parative proteome analysis of normal and HIV-positive plasma samples, 19 differentially expressed protein spots related to 12 non-redundant proteins were identified by ESI-ion trap MS. Among these, the 130-kDa isoform of α-1-antitrypsin was found to be decreased in HIV-positive patients while another variant with a molecular weight of 40 kDa was increased. SWISS-2-D-PAGE reference gel and protein parisons of the 40-kDa protein showed homology with α-1-antitrypsin minus the N-terminus, and its identity was further confirmed by 1-D Western blotting and glycoproteomic analysis. In all, our results showed that proteomics and glycoproteomics are powerful tools for discovering proteins related to HIV infection. Furthermore, this 40-kDa variant of α-1-antitrypsin found in the plasma of HIV-positive individuals may prove to be a potentially useful biomarker for anti-HIV research according to bioinformatics analysis. |
20859953 | Chromatographic determination of solubilities in superheated water. | Superheated water (SHW) is an effective solvent for the extraction of a variety of environmental pollutants, but knowledge of the solubilities in water at elevated temperatures necessary to maximise the efficiency of the process is often lacking. Ambient temperature aqueous solubilities have been measured by reverse-phase HPLC from correlations with retention factors, k, but for poorly soluble organics the eluent must contain a proportion of organic modifier followed by extrapolation to pure water. The use of SHW as mobile phase allows direct determination of aqueous solubility from measurement of k on a modified HPLC system in which the eluent is cooled before detection to improve baseline stability. Alumina-bonded octadecylsilane columns were found to be more stable in SHW chromatography than their silica-bonded counterparts. To validate the procedure, measurements of k were made between 100 and 200°C for toluene and correlated with literature solubilities; the solubilities at 170°C of a number of related aromatics were then determined from their k-values. |
20859954 | Simultaneous capillary electrophoretic analysis of inorganic anions and cations in post-blast extracts of acid-aluminum mixtures. | Bursts resulting from the chemical reaction between hydrochloric or nitric acid with aluminum foils are very mitted by the young delinquency in western countries because of its easiness of achievement. A fast, simple, selective, and cost-effective method allowing the simultaneous detection of chloride and nitrate anions and aluminum(III) was thus required. This article focused on the development and validation of a CE method using a BGE containing 2,6-pyridinedicarboxylic acid (PDC) acting as both an anionic chromophore and as an plexing agent. First, the achievement of the speciation diagram of Al(III) in the presence of PDC allowed the choice of pH conditions for which aluminum(III) was globally anionic. The study of the selectivity for Al(III) in the presence of ten other cationic species potentially present in post-blast residues dictated the choice of the PDC concentration at 20 mM. The validation step next demonstrated the figures of merit of the method, with an intermediate precision for Al(III) of 2% on normalized migration times and 3.5% on corrected areas. Finally, this method was used for analyses of real post-blast extracts from acid-aluminum mixtures. |
20859955 | A simplified method for the determination of total homocysteine in plasma by electrospray tandem mass spectrometry. | Hyperhomocysteinemia is a risk factor for different diseases. Several methods have been developed to analyze homocysteine and the immunometric ones, although expensive, they are in widespread use. A rapid LC-MS/MS method for homocysteine assay has been developed for the application of large clinical chemistry routines. Selected reaction monitoring was performed through the transitions m/z 136.0→90.1 for homocysteine and m/z 140.0→94.0 for the internal standard. ESI was used to generate [H+] adduct ions. Chromatographic isocratic separation was achieved using a strong cation exchange column. The mobile phase was methanol/water (20:80 v/v, containing 0.1% formic acid and 1.5 mmol/L ammonium formate in the water phase) at a flow rate of 0.250 mL/min (35°C). Samples treatment consisted in the reduction with DTT and deproteinization with methanol. Recovery, linearity, LOD, LOQ and total imprecision were evaluated to validate the method. Homocysteine values on 100 serum samples pared with those obtained by HPLC and immunometric methods. The method is robust, selective and precise in the whole range of values studied. Moreover, low reagent cost and easiness of sample treatment make this method useful, not only for research, but also for routine work. |
20859956 | Proteomic identification of microRNA-122a target proteins in hepatocellular carcinoma. | MicroRNA-122a (miR-122a) is a liver-specific miRNA that is frequently downregulated in hepatocellular carcinoma (HCC). The exact functional role of miR-122a and its target in HCC remain largely unknown. We developed a lentiviral vector for the expression of pre-miR-122a (Lenti-miR-122a). Lenti-miR-122a inhibited HCC cell growth and induced apoptosis in vitro. We employed proteomic profiling to identify the target proteins of miR-122a. In total, ten proteins with differential expression in HCC cells infected with Lenti-miR-122a were identified. Amongst them, downregulation of peroxiredoxin 2 (PRDXII) by miR-122a was validated by Western blotting. Using bioinformatics analysis, predictable target sites of miR-122a were identified in the 5'-UTR of PRDXII mRNA. Luciferase reporter assay confirmed the regulation of miR-122a on 5'-UTR of PRDXII. In conclusion, PRDXII was identified to be the new target of miR-122a. |
20859957 | Development of a new method using HILIC-tandem mass spectrometry for the characterization of O-sialoglycopeptides from proteolytically digested caseinomacropeptide. | This work addresses the optimization of HILIC (hydrophilic interaction liquid chromatography)-ESI-MS(n) conditions for prehensive characterization of O-glycopeptides from proteolytically digested caseinomacropeptide. O-Glycopeptides were satisfactorily analysed on a zwitterionic HILIC column based on their glycan structure and amino acid sequence. The contribution of ionic interactions to the retention of charged glycopeptides was found to be substantial. Thus, O-glycopeptides carrying neutral glycans were more retained than O-sialoglycopeptides because negatively charged sialic acid residues were electrostatically repelled by the stationary phase. In addition, glycopeptides differing only in the position of the linkage of the sialic acid moiety could be separated. The same chromatographic behaviour was observed for model systems constituted by a synthetic tetrapeptide covalently conjugated to neutral and sialylated carbohydrates. Subsequent detection of caseinomacropeptide O-glycopeptides was carried out on an electrospray ion trap tandem mass spectrometer at both positive and negative ionization modes. MS(2) fragmentation at positive ionization mode was valid for determining the glycan structure as the resulting main fragments corresponded to Y(n)-type ions derived from sequential glycosidic bond fragmentation, whilst the fragmentation of the peptide structure was preferably obtained through the formation of b(n)-type ions at the MS(3) stage, allowing plete structure elucidation of the peptidic chain. Overall, the developed method allowed the identification and characterization of 41 O-glycopeptides covering all the known glycosylation sites without any previous enrichment step. These results point out that HILIC coupled to multistage MS procedures can be a powerful technique for future glycoproteomic applications. |
20859958 | Achievements and perspectives of top-down proteomics. | Over the last years, top-down (TD) MS has gained a remarkable space in proteomics, rapidly trespassing the limit between a promising approach and a solid, established technique. Several research groups worldwide have implemented TD analysis in their routine work on proteomics, deriving structural information on proteins with the level of accuracy that is impossible to achieve with classical bottom-up approaches. Complete maps of PTMs and assessment of single aminoacid polymorphisms are only a few of the results that can be obtained with this technique. Despite some existing technical and economical limitations, TD analysis is at present the most powerful instrument for MS-based proteomics and its implementation in routine workflow is a rapidly approaching turning point in proteomics. In this review article, the state-of-the-art of TD approach is described along with its major advantages and drawbacks and the most recent trends in TD analysis are discussed. References for all the covered topics are reported in the text, with the aim to support both ers and mass spectrometrists already introduced to TD proteomics. |
20859959 | High-efficiency nano- and micro-HPLC--high-resolution Orbitrap-MS platform for top-down proteomics. | In terms of resolution, mass accuracy, and sensitivity, the Orbitrap represents one of the most potent mass analyzers available today. We here elucidate the potential of interfacing Orbitrap-MS to ion-pair RP HPLC for intact protein analysis. Using gradients of ACN and monolithic columns of 1.0 and 0.10 mm id, peak capacities between 120 and 130 were achievable within 20-25 min separation time. Compared with silica-based stationary phases, protein recovery and carryover from monolithic columns were found clearly superior. Intact proteins were detectable in a mass range covering 5.7-150 kDa with LODs in the low femtomol range. Compared with UV detection, MS detection with a scanning speed of 1.6 s per spectrum on average led to a 26% increase in chromatographic peak widths, whereas chromatographic patterns were mostly preserved in extracted ion chromatograms at an acquisition rate of 0.5 s per spectrum. Isotopic resolution of multiply charged ions was demonstrated for proteins up to 42 kDa. A micro-HPLC-Orbitrap-MS setup employing a 1.0 mm id column was utilized to characterize a 150 kDa binant monoclonal antibody. The applicability of nano-HPLC-Orbitrap-MS to the analysis of plex protein mixtures is demonstrated for the 70% ethanol extractable subproteome of wheat grains. |
20859961 | Syntheses and photophysical properties of N-pyridylimidazol-2-ylidene tetracyanoruthenates(II) and photochromic studies of their dithienylethene-containing derivatives. | A series of tetracyanoruthenate(II) with chelating pyridyl N-heterocyclic carbene ligands (NHC-py) was synthesized and characterized. Their photophysical and electrochemical properties as well as the photochromic behavior of their plexes were studied. Photocyclization was found to take place upon irradiation into the metal-to-ligand charge transfer (MLCT) absorption bands of plexes, and evidence is provided to support the triplet-sensitizing reaction pathway. |
20859960 | The crystal structure of non-modified and bipyridine-modified PNA duplexes. | Peptide nucleic acid (PNA) is a synthetic analogue of DNA monly has an N-aminoethyl glycine backbone. The crystal structures of two PNA duplexes, one containing eight standard nucleobase pairs (GGCATGCC)(2), and the other containing the same nucleobase pairs and a central pair of bipyridine ligands, have been solved with a resolution of 1.22 and 1.10 Å, respectively. The non-modified PNA duplex adopts a P-type helical structure similar to that of previously characterized PNAs. The atomic-level resolution of the structures allowed us to observe for the first time specific modes of interaction between the terminal lysines of the PNA and the backbone and the nucleobases situated in the vicinity of the lysines, which are considered an important factor in the induction of a preferred handedness in PNA duplexes. Our results support the notion that whereas PNA typically adopts a P-type helical structure, its flexibility is relatively high. For example, the base-pair rise in the bipyridine-containing PNA is the largest measured to date in a PNA homoduplex. The two bipyridines bulge out of the duplex and are aligned parallel to the major groove of the PNA. In addition, two bipyridines from adjacent PNA duplexes form a π-stacked pair that relates the duplexes within the crystal. The bulging out of the bipyridines causes bending of the PNA duplex, which is in contrast to the structure previously reported for biphenyl-modified DNA duplexes in solution, where the biphenyls are π stacked with adjacent nucleobase pairs and adopt an intrahelical geometry. This difference shows that relatively small perturbations can significantly impact the relative position of nucleobase analogues in nucleic acid duplexes. |
20859962 | Solution structure, mechanism of replication, and optimization of an unnatural base pair. | As part of an ongoing effort to expand the genetic alphabet for in vitro and eventual in vivo applications, we have synthesized a wide variety of predominantly hydrophobic unnatural base pairs and evaluated their replication in DNA. Collectively, the results have led us to propose that these base pairs, which lack stabilizing edge-on interactions, are replicated by means of a unique intercalative mechanism. Here, we report the synthesis and characterization of three novel derivatives of the nucleotide analogue dMMO2, which forms an unnatural base pair with the nucleotide analogue d5SICS. Replacing the para-methyl substituent of dMMO2 with an annulated furan ring (yielding dFMO) has a dramatically negative effect on replication, while replacing it with a methoxy (dDMO) or with a thiomethyl group (dTMO) improves replication in both steady-state assays and during PCR amplification. Thus, dTMO-d5SICS, and especially dDMO-d5SICS, represent significant progress toward the expansion of the genetic alphabet. To elucidate the structure-activity relationships governing unnatural base pair replication, we determined the solution structure of duplex DNA containing the parental dMMO2-d5SICS pair, and also used this structure to generate models of the derivative base pairs. The results strongly support the intercalative mechanism of replication, reveal a surprisingly high level of specificity that may be achieved by optimizing packing interactions, and should prove invaluable for the further optimization of the unnatural base pair. |
20859963 | The total synthesis of (±)-fumimycin. | The antibiotic agent fumimycin has been synthesized for the first time. This natural product was found to inhibit the bacterial peptide deformylase and may represent a lead structure to a class of novel antibacterials. Our synthetic strategy towards fumimycin involved the following steps: Dakin oxidation of an aldehyde functionality, conversion of an oxime through radical fragmentation to form an N-diphenylphosphoryl group, construction of an α-trisubstituted amine by 1,2-addition to a ketimine, a Claisen rearrangement with subsequent transition-metal-catalyzed olefin isomerization to install a propenyl chain and final amidation. |
20859964 | High-yielding synthesis of the anti-influenza neuraminidase inhibitor (-)-oseltamivir by two "one-pot" sequences. | The efficient asymmetric total synthesis of (-)-oseltamivir, an antiviral reagent, has been plished by using two "one-pot" reaction sequences, with excellent overall yield (60 %) and only one required purification by column chromatography. The first one-pot reaction sequence consists of a diphenylprolinol silyl ether mediated asymmetric Michael reaction, a domino Michael reaction/Horner-Wadsworth-Emmons bined with retro-aldol/Horner-Wadsworth-Emmons reaction and retro Michael reactions, a thiol Michael reaction, and a base-catalyzed isomerization. Six reactions can be successfully conducted in the second one-pot reaction sequence; these are deprotection of a tert-butyl ester and its conversion into an acyl chloride then an acyl azide, Curtius rearrangement, amide formation, reduction of a nitro group into an amine, and a retro Michael reaction of a thiol moiety. A column-free synthesis of (-)-oseltamivir has also been established. |
20859965 | A facile route to metal nitride clusterfullerenes by using guanidinium salts: a selective organic solid as the nitrogen source. | Using guanidinium salts 1 and 2 as the new nitrogen sources, metal nitride clusterfullerenes (NCFs) based on a variety of metals (Dy, Sc, Y, Gd, Lu, and mixed metals Sc/Dy, Sc/Gd, Sc/Lu, and Lu/Ce) have been synthesized based on a new "selective organic solid" (SOS) route. The synthesis of Dy-NCFs by using Dy/1 was studied in detail, and the optimum molar ratio of 1/Dy/C has been determined to be 2.5:1:10. For several representative metals such as Sc, Y, Gd, Dy, and Sc/Dy, we pared the yield of M(3)N@C(80) synthesized by the SOS route with the reported "reactive gas atmosphere" route, thereby indicating that the yield of M(3)N@C(80) by using 1 could parable to that obtained by the reactive gas atmosphere route. Three other nitrogen sources (3-5) were also studied parison, which were mixed with Dy metal but did not result in the formation of Dy-NCF. A possible reaction scheme for the solid-state reaction of 1, metal, and graphite is proposed. The SOS route appears to be a general route for the synthesis of NCFs that promises both high selectivity of NCFs and high reproducibility of the fullerene yield. Another advantages of the SOS pared to the reported "trimetallic nitride template" (TNT) process and the reactive gas atmosphere route is that no additional heating pretreatment is needed, thus simplifying the procedure and being much more facile. |
20859966 | A general synthesis of alkenyl-substituted benzofurans, indoles, and isoquinolones by cascade palladium-catalyzed heterocyclization/oxidative Heck coupling. | Structurally diverse C3-alkenylbenzofurans, C3-alkenylindoles, and C4-alkenylisoquinolones are efficiently prepared by using consecutive Sonogashira and cascade Pd-catalyzed heterocyclization/oxidative Heck couplings from readily available ortho-iodosubstituted phenol, aniline, and benzamide substrates, alkynes, and functionalized olefins. The cyclization of O- and N-heteronucleophiles follows regioselective 5-endo-dig- or 6-endo-dig-cyclization modes, whereas the subsequent Heck-type coupling with both mono- and disubstituted olefins takes place stereoselectively with exclusive formation of the E isomers in most cases. |
20859969 | Molecular gallium arsenide phosphide clusters prepared from AsP(3), P(4), and [{GaC(SiMe(3))(3)}(4)]. | Treatment of AsP(3) with 0.75 equivalents of [{GaC(SiMe(3))(3)}(4)] resulted in selective insertion of three equivalents of {GaC(SiMe(3))(3)} into the three As--P bonds to give [As{GaC(SiMe(3))(3)}(3)P(3)] (1-As) with an intact cyclo-P(3) ring. This pound has been characterized by NMR bustion analysis, single-crystal X-ray diffraction, UV/Vis spectroscopy, Raman spectroscopy, and cyclic voltammetry (THF, 0.2 M [TBA][B(C(6)F(5))(4)]; TBA=tetrabutyl ammonium). Computational models of 1-As and the isomeric [P{GaC(SiMe(3))(3)}(3)AsP(2)] (1-P) have been investigated as well, revealing several interesting electronic features of these cage molecules. Following from the cyclic voltammetry studies of 1-As that highlight an irreversible two-electron reduction at -2.2 V versus Fc/Fc(+), treatment with one equivalent of [Mg(C(14)H(10))(thf)(3)] resulted in two-electron reduction to provide [As{GaC(SiMe(3))(3)}(3)P(3)Mg(thf)(3)] (2), in which the Mg(2+) ion has inserted into one of the P--P bonds of the cyclo-P(3) ring. It was also found that treatment of AsP(3) or P(4) with one equivalent of [{GaC(SiMe(3))(3)}(4)] resulted in formation of the quadruple insertion products [As{GaC(SiMe(3))(3)}(4)P(3)] (3) and [P{GaC(SiMe(3))(3)}(4)P(3)] (4), respectively. |
20859968 | Cyclization of zincated α-N-homoallylamino nitriles: a new entry to enantiopure 2,3-methanopyrrolidines. | Stereoselective cyclization of zincated α-N-homoallylamino nitriles has been developed. Following treatment with lithium diisopropylamide (LDA) and transmetalation with zinc bromide, α-N-(1-phenylethyl)-N-homoallylamino nitriles lead to 2,3-methanopyrrolidines in moderate to good yields (up to 66 %) and excellent selectivities (up to >98:2). With substrates derived from α-branched homoallylic amines, a stereospecific inversion of the homoallylic stereogenic center was observed. To account for this, a mechanistic rationale involving the formation of zincioiminium ions from zincated α-amino nitriles is put forward. 2,3-Methanopyrrolidines should then arise from a sequence involving an aza-Cope rearrangement providing a configurationally stable (2-azoniaallyl)zinc species that then undergoes a [3+2] cycloaddition reaction. |
20859967 | Glyco-pseudopolyrotaxanes: carbohydrate wheels threaded on a polymer string and their inhibition of bacterial adhesion. | We report posed of cucurbit[6]uril-based mannose wheels (ManCB[6]) threaded on polyviologen (PV), which not only effectively induce bacterial aggregation, but also exhibit high inhibitory activity against bacterial binding to host cells. Three glyco-pseudopolyrotaxanes (1-3), which have 10, 5, and 3 ManCB[6] wheels, respectively, on a PV string, were prepared and characterized. Bacterial aggregation assays and hemagglutination inhibition assays illustrated the specific and multivalent interaction between the glyco-pseudopolyrotaxanes and E. coli ORN178. Compound 3 was especially effective at inducing bacterial aggregation and showed 300 times higher inhibitory potency than monomeric methyl-α-mannoside (Me-αMan) for ORN178-induced hemagglutination. Furthermore, we demonstrated their inhibitory activities for the adhesion of ORN178 bacteria to urinary epithelial cells as a model of urinary tract infection. Our findings suggest that these supramolecular carbohydrate clusters are potentially useful in antiadhesion therapy. |
20859972 | A continuous flow process using a sequence of microreactors with in-line IR analysis for the preparation of N,N-diethyl-4-(3-fluorophenylpiperidin-4-ylidenemethyl)benzamide as a potent and highly selective δ-opioid receptor agonist. | This article describes the design, optimisation and development of a continuous flow synthesis of N,N-diethyl-4-(3-fluorophenylpiperidin-4-ylidenemethyl)benzamide, a potent δ-opioid receptor agonist developed by AstraZeneca. The process employs a sequence of flow-based microreactors, with integrated purification employing solid-supported reagents and in-line IR analytical protocols using a newly developed ReactIR flow cell. With this monitoring device, initiation of the fourth input flow stream can be precisely controlled during the synthesis. |
20859975 | Factors determining the selection of organic reactions by medicinal chemists and the use of these reactions in arrays (small focused libraries). | Synthetic organic reactions are a fundamental enabler of small-molecule drug discovery, and the vast majority of medicinal chemists are initially trained--either at universities or within industry--as synthetic organic chemists. The sheer breadth of synthetic methodology available to the medicinal chemist represents an almost endless source of innovation. But what reactions do medicinal chemists use in drug discovery? And what criteria do they use in selecting synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead-optimization process? In this Minireview, we suggest some answers to these questions and also describe how we have tried to expand the number of robust reactions available to the medicinal chemist. |
20859985 | Templated chemistry for sequence-specific fluorogenic detection of duplex DNA. | We describe the development of templated fluorogenic chemistry for detection of specific sequences of duplex DNA in solution. In this approach, two modified homopyrimidine oligodeoxynucleotide probes are designed to bind by triple-helix formation at adjacent positions on a specific purine-rich target sequence of duplex DNA. One fluorescein-labeled probe contains an α-azidoether linker to a fluorescence quencher; the second (trigger) probe carries a triarylphosphine group that is designed to reduce the azide and cleave the linker. The data showed that at pH 5.6 these probes yielded a strong fluorescence signal within minutes on addition to plementary homopurine duplex DNA target. The signal increased by a factor of about 60, and pletely dependent on the presence of the target DNA. Replacement of cytosine in the probes with pseudoisocytosine allowed the templated chemistry to proceed readily at pH 7. Single nucleotide mismatches in the target oligonucleotide slowed the templated reaction considerably; this demonstrated high sequence selectivity. The use of templated fluorogenic chemistry for detection of duplex DNAs has not been previously reported and could allow detection of double-stranded DNA, at least for homopurine-homopyrimidine target sites, under native and nondenaturing conditions. |
20859987 | Novel huprine derivatives with inhibitory activity toward β-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates. | A new family of dual binding site acetylcholinesterase (AChE) inhibitors has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced β-amyloid (Aβ) aggregation and β-secretase (BACE-1), and to cross the blood-brain barrier. The new heterodimers consist of a unit of racemic or enantiopure huprine Y or X and a donepezil-related 5,6-dimethoxy-2-[(4-piperidinyl)methyl]indane moiety as the active site and peripheral site to mid-gorge-interacting moieties, respectively, connected through a short oligomethylene linker. Molecular dynamics simulations and kinetics studies support the dual site binding to AChE. The new heterodimers are potent inhibitors of human AChE and moderately potent inhibitors of human BChE, AChE-induced and self-induced Aβ aggregation, and BACE-1, and are predicted to be able to enter the central nervous system (CNS), thus constituting promising multitarget anti-Alzheimer drug candidates with the potential to modify the natural course of this disease. |
20859988 | The effect of germination on the phytase activity, phytate and total phosphorus contents of some Nigerian-grown grain legumes. | Grain legumes are under-exploited as possible sources of phytase for the poultry industry. The current study was conducted to assess the effect of germination on phytase activities, phytate and total phosphorus content in samples of Nigerian-grown grain legumes. The legumes screened were African yambean (AYB, Sphenostylis stenocarpa), lima bean (Phaseolus lunatus), pigeon pea (Cajanus cajan), cowpea (Vigna unguiculata) and groundnut (Arachis hypogea). |
20859991 | Transcriptional coactivators p300 and CBP stimulate estrogen receptor-beta signaling and regulate cellular events in prostate cancer. | Steroid receptor coactivators p300 and CBP are highly expressed in advanced prostate cancer. They potentiate activation of androgen receptor by androgens and anti-androgens. In the present study, we have addressed the question whether these coactivators enhance activity of estrogen receptor-beta (ER-β), which is variably expressed in prostate cancers. |
20859993 | Influence of brain tumors on the MR spectra of healthy brain tissue. | The neurochemical environment of nontumorous white matter tissue was investigated in 135 single voxel spectra of "healthy" white matter regions of 43 tumor patients and 129 spectra of 52 healthy subjects. Spectra were acquired with short TE and TR values. With the data of tumor patients, it was examined whether differences were caused by the tumor itself or aggressive tumor therapies as confounding factors. Comparing the spectra of both classes, an excellent differentiation was possible based on the metabolite peak of N-acetylaspartate (P ≈ 0) and myoinositol (P < 0.03). The area under curve of the receiver operating characteristic was calculated as 0.86 and 0.62, respectively. With linear discriminant analysis binations of integrals, a prediction was possible, whether a spectrum belonged to the patient or the healthy subject class with an overall accuracy above 80%. The confounding factors could be ruled out as source of the differences. The results show strong evidence for an influence of malignant growth on the biochemical environment of nontumorous white matter tissue. Because of the T(1) weighting, the measured differences between both classes were most likely concentration changes interfered by T(1) effects. The underlying processes will be subject of future studies. |
20859992 | Receptors for luteinizing hormone-releasing hormone (LHRH) in benign prostatic hyperplasia (BPH) as potential molecular targets for therapy with LHRH antagonist cetrorelix. | The majority of men will develop symptoms of benign prostatic hyperplasia (BPH) after 70 years of age. Various studies indicate that antagonists of LHRH, such as cetrorelix, exert direct inhibitory effects on BPH mediated by specific LHRH receptors. Our aim was to investigate the mRNA for LHRH and LHRH receptors and the expression of LHRH receptors in specimens of human BPH. |
20859994 | Immobilized contrast-enhanced MRI: Gadolinium-based long-term MR contrast enhancement of the vein graft vessel wall. | An implantable MR contrast agent that can be covalently immobilized on tissue during surgery has been developed. The rationale is that a durable increase in tissue contrast using an implantable contrast agent can enhance postsurgical tissue differentiation using MRI. For small-vessel (e.g., vein graft) MRI, the direct benefit of such permanent "labeling" of the vessel wall by modification of its relaxation properties is to achieve more efficient imaging. This efficiency can be realized as either increased contrast leading to more accurate delineation of vessel wall and lesion tissue boundaries, or, faster imaging without penalizing contrast-to-noise ratio, or bination thereof. We demonstrate, for the first time, stable long-term MRI enhancement using such an exogenous contrast mechanism based on immobilizing a modified diethylenetriaminepentaacetic acid gadolinium(3+) plex on a human vein using a covalent amide bond. Signal enhancement due to the covalently immobilized contrast agent is demonstrated for excised human vein specimens imaged at 3 T, and its long-term stability is demonstrated during a 4-month incubation period. |
20859989 | Evaluation of a guided internet self-treatment programme for bulimia nervosa in several European countries. | The purposes of this study were to evaluate the use of an online guided self-treatment programme for bulimia nervosa (BN) and to determine predictors of e. Data were collected in four European countries where the programme was simultaneously used. |
20859995 | An analytical description of balanced steady-state free precession with finite radio-frequency excitation. | Conceptually, the only flaw in the standard steady-state free precession theory is the assumption of quasi-instantaneous radio-frequency pulses, and 10-20% signal deviations from theory are observed mon balanced steady-state free precession protocols. This discrepancy in the steady-state signal can be resolved by a simple T(2) substitution taking into account reduced transverse relaxation effects during finite radio-frequency excitation. However, finite radio-frequency effects may also affect the transient phase of balanced steady-state free precession, its contrast or its spin-echo nature and thereby have an adverse effect mon steady-state free precession magnetization preparation methods. As a result, an in-depth understanding of finite radio-frequency effects is not only of fundamental theoretical interest but also has direct practical implications. In this article, an analytical solution for balanced steady-state free precession with finite radio-frequency pulses is derived for the transient phase (under ideal conditions) and in the steady state demonstrating that balanced steady-state free precession key features are preserved but revealing an unexpected dependency of finite radio-frequency effects on relaxation times for the transient decay. Finally, the mathematical framework reveals that finite radio-frequency theory can be understood as a generalization of alternating repetition time and fluctuating equilibrium steady-state free precession sequence schemes. |
20859996 | Post-processing correction of magnetization transfer effects in FENSI perfusion MRI data. | Magnetization transfer effects induced by repetitive saturation pulses employed in flow enhancement of signal intensity imaging sequences currently prevent quantitative, in vivo, cerebral perfusion studies. This study investigates the magnitude of these effects and introduces a post-processing correction protocol. The study shows that the magnetization transfer effect is consistent across individuals, which enables the derivation of a correction factor to be applied in post-acquisition. Our results, obtained for cerebral flux in white and gray matter in rodent brains, are in agreement with cerebral blood flow measurements previously reported in the literature. |
20859990 | Enhanced cognitive behavioural therapy for an adolescent with purging disorder: a case report. | To present a case report detailing the use of an enhanced form of cognitive behaviour therapy (CBT). The treatment was provided to an adolescent with an eating disorder not otherwise specified (EDNOS) diagnosis, and included a focus on the additional maintaining mechanisms of mood intolerance and interpersonal problems. |
20859997 | Longitudinal MR assessment of hypoxic ischemic injury in the immature rat brain. | Extremely preterm monly show brain injury with long-term structural and functional consequences. Three-day-old (P3) rat pups share some similarities in terms of cerebral development with the very preterm infant (born at 24-28 weeks of gestation). The aim of this study was to assess longitudinally the cerebral structural and metabolic changes resulting from a moderate neonatal hypoxic ischemic injury in the P3 rat pup using high-field (9.4 T) MRI and localized (1) H magnetic resonance spectroscopy techniques. The rats were scanned longitudinally at P3, P4, P11, and P25. Volumetric measurements showed that the percentage of cortical loss in the long term correlated with size of damage 6 h after hypoxia-ischemia, male pups being more affected than female. The neurochemical profiles revealed an acute decrease of most of metabolite concentrations and an increase in lactate 24 h after hypoxia-ischemia, followed by a recovery phase leading to minor metabolic changes at P25 in spite of an abnormal brain development. Further, the increase of lactate concentration at P4 correlated with the cortical loss at P25, giving insight into the early prediction of long-term cerebral alterations following a moderate hypoxia-ischemia insult that could be of interest in clinical practice. |
20859998 | Compressed sensing for chemical shift-based water-fat separation. | Multi echo chemical shift-based water-fat separation methods allow for uniform fat suppression in the presence of main field inhomogeneities. However, these methods require additional scan time for chemical shift encoding. This work presents a method for water-fat separation from undersampled data (CS-WF), pressed sensing and chemical shift-based water-fat separation. Undersampling was applied in the k-space and in the chemical shift encoding dimension to reduce the total scanning time. The method can reconstruct high quality water and fat images in 2D and 3D applications from undersampled data. As an extension, multipeak fat spectral models were incorporated into the CS-WF reconstruction to improve the water-fat separation quality. In 3D MRI, reduction factors of above three can be achieved, thus pensating the additional time needed in three-echo water-fat imaging. The method is demonstrated on knee and abdominal in vivo data. |
20859999 | Prognostic value of heparanase expression and cellular localization in oral cancer. | Metastases formation depends on the ability of tumor cells to invade basement membranes in a process involving enzymes capable of degrading extracellular ponents. |
20860000 | Mapping of redox status in a brain-disease mouse model by three-dimensional EPR imaging. | Electron paramagnetic resonance imaging using nitroxides is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. Typically, however, data acquisition times have been too slow to obtain a sufficient number of projections for three-dimensional images, when using continuous wave-electron paramagnetic resonance imager in small rodents, using nitroxides paratively short T(2) and a half-life values. Because of improvements in imagers that enable rapid data-acquisition, the feasibility of three-dimensional electron paramagnetic resonance imaging with good quality in mice was tested with nitroxides. Three-dimensional images of mice were obtained at an interval of 15 sec under field scanning of 0.3 sec and with 46 projections in the case of strong electron paramagnetic resonance signals. Three-dimensional electron paramagnetic resonance images of a blood brain barrier-permeable nitroxide, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, in the mouse head clearly showed that 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl was distributed within brain tissues, and this was confirmed by MRI observations. Based on the pharmacokinetics of nitroxides in mice, half-life mapping was demonstrated in an ischemia-reperfusion model mouse brain. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in mouse head under oxidative stress by the improved continuous wave-electron paramagnetic resonance imager noninvasively. |
20860003 | Highly accelerated contrast-enhanced MR angiography: improved reconstruction accuracy and reduced noise amplification with complex subtraction. | Contrast-enhanced magnetic resonance angiography is routinely performed using parallel imaging to best capture the first pass of contrast material through the target vasculature, followed by digital subtraction to suppress the appearance of unwanted signal from background tissue. Both processes, however, amplify noise and can produce uninterpretable images when large acceleration factors are used. Using a phantom study of contrast-enhanced magnetic resonance angiography, we show plex subtraction processing prior to partially parallel reconstruction improves reconstruction accuracy relative to magnitude subtraction processing for reduction factors as large as 12. Time-resolved contrast-enhanced magnetic resonance angiographic data obtained plex subtraction in volunteers supported the results of the phantom study and pared with magnitude subtraction processing demonstrated reduced geometry factors as well as improved image quality at large reduction factors. |
20860001 | Dynamic contrast-enhanced MRI of neuroendocrine hepatic metastases: A feasibility study using a dual-input two-compartment model. | Neuroendocrine hepatic metastases exhibit various contrast uptake enhancement patterns in dynamic contrast-enhanced MRI. Using a dual-input partment distributed parameter model, we analyzed the dynamic contrast-enhanced MRI datasets of seven patient study cases with the aim to relate the tumor contrast uptake patterns to parameters of tumor microvasculature. Simulation studies were also performed to provide further insights into the effects of individual microcirculatory parameter on the tumor concentration-time curves. Although the tumor contrast uptake patterns can be influenced by many parameters, initial results indicate that hepatic blood flow and the ratio of fractional vascular volume to fractional interstitial volume may potentially distinguish between the patterns of neuroendocrine hepatic metastases. |
20860002 | Brain MR perfusion-weighted imaging with alternate ascending/descending directional navigation. | In this study, a new arterial spin labeling technique that requires no separate spin preparation pulse was developed. Sequential two-dimensional slices were acquired in ascending and descending orders by turns using balanced steady state free precession for pair-wise subtraction. Simulation studies showed this new technique, alternate ascending/descending directional navigation (ALADDIN), has high sensitivity to both slow- (1-10 cm/sec) and fast-moving (>10 cm/sec) blood because of the presence of multiple labeling planes proximal to imaging planes and sensitivity of balanced steady state free precession to initial magnetization differences. ALADDIN provided high-resolution multislice perfusion-weighted images in ∼ 3 min. About 80-90% of signals in a slice were ascribed to spins saturated in the four prior slices. Three to five edge slices on each side of imaging group were affected by transient magnetization transfer effects and plete T(1) recovery between successive acquisitions. ALADDIN signals were dependent on many imaging parameters, implying room for improvement. Sagittal and coronal ALADDIN images demonstrated perfusion direction in gray matter regions was mostly from center to lateral, anterior, or posterior, whereas that in some white matter regions was reversed. ALADDIN is likely useful for many studies requiring perfusion-weighted imaging with short scan time, insensitiveness to arterial transit time, directional information, high resolution, and/or wide coverage. |
20860004 | Assessment of multiexponential diffusion features as MRI cancer therapy response metrics. | The aim of this study was to empirically test the effect of chemotherapy-induced tissue changes in a glioma model as measured by several diffusion indices calculated from nonmonoexponential formalisms over a wide range of b-values. We pared these results to the conventional two-point apparent diffusion coefficient calculation using nominal b-values. Diffusion-weighted imaging was performed over an extended range of b-values (120-4000 sec/mm(2) ) on intracerebral rat 9L gliomas before and after a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea. Diffusion indices from three formalisms of diffusion-weighted signal decay [(a) two-point analytical calculation using either low or high b-values, (b) a stretched exponential formalism, and (c) a biexponential fit] were tested for responsiveness to therapy-induced differences between control and treated groups. Diffusion indices sensitive to "fast diffusion" produced the largest response to treatment, which resulted in significant differences between groups. These trends were not observed for "slow diffusion" indices. Although the highest rate of response was observed from the biexponential formalism, this was not found to be significantly different from the conventional monoexponential apparent diffusion coefficient method. In conclusion, parameters from the plicated nonmonoexponential formalisms did not provide additional sensitivity to treatment response in this glioma model beyond that observed from the two-point conventional monoexponential apparent diffusion coefficient method. |
20860006 | Dual-echo Dixon imaging with flexible choice of echo times. | In this work, a new two-point method for water-fat imaging is described and explored. It generalizes existing two-point methods by eliminating some of the restrictions that these methods impose on the choice of echo times. Thus, the new two-point method promises to provide more freedom in the selection of protocol parameters and to reach higher scan efficiency. Its performance was studied theoretically and was evaluated experimentally in abdominal imaging with a multigradient-echo sequence. While depending on the choice of echo times, it is generally found to be pared to existing two-point methods. Notably, water images with higher spatial resolution and better signal-to-noise ratio were attained with it in single breathholds at 3.0 T and 1.5 T, respectively. The use of more accurate spectral models of fat is shown to substantially reduce observed variations in the extent of fat suppression. The acquisition of in- and opposed-phase images is demonstrated to be replaceable by a synthesis from water and fat images. The new two-point method is finally also applied to autocalibrate a multidimensional eddy current correction and to enhance the fat suppression achieved with three-point methods in this way, especially toward the edges of larger field of views. |
20860008 | A new method to provide a fresh frozen prostate slice suitable for gene expression study and MR spectroscopy. | Fresh frozen tissue from radical prostatectomy specimens is highly valuable material for research on gene expression and cellular metabolites. The purpose of this study was to develop a standardized method to provide a representative high quality research sample from radical prostatectomy specimens without interfering with the routine histopathological procedure. |
20860007 | In vivo observation of intracellular oximetry in perfluorocarbon-labeled glioma cells and chemotherapeutic response in the CNS using fluorine-19 MRI. | Preclinical development of therapeutic agents against cancer could greatly benefit from noninvasive markers of tumor killing. Potentially, the intracellular partial pressure of oxygen (pO(2) ) can be used as an early marker of antitumor efficacy. Here, the feasibility of measuring intracellular pO(2) of central nervous system glioma cells in vivo using (19) F magnetic resonance techniques is examined. Rat 9L glioma cells were labeled with perfluoro-15-crown-5-ether ex vivo and then implanted into the rat striatum. (19) F MRI was used to visualize tumor location in vivo. The mean (19) F T(1) of the implanted cells was measured using localized, single-voxel spectroscopy. The intracellular pO(2) in tumor cells was determined from an in vitro calibration curve. The basal pO(2) of 9L cells (day 3) was determined to be 45.3 ± 5 mmHg (n = 6). Rats were then treated with a 1 × LD10 dose of bischloroethylnitrosourea intravenously and changes in intracellular pO(2) were monitored. The pO(2) increased significantly (P = 0.042, paired T-test) to 141.8 ± 3 mmHg within 18 h after bischloroethylnitrosourea treatment (day 4) and remained elevated (165 ± 24 mmHg) for at least 72 h (day 6). Intracellular localization of the perfluoro-15-crown-5-ether emulsion in 9L cells before and after bischloroethylnitrosourea treatment was confirmed by histological examination and fluorescence microscopy. Overall, noninvasive (19) F magnetic resonance techniques may provide a valuable preclinical tool for monitoring therapeutic response against central nervous system or other deep-seated tumors. |
20860009 | Prostate cancer risk alleles significantly improve disease detection and are associated with aggressive features in patients with a "normal" prostate specific antigen and digital rectal examination. | Several reports suggest that bination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a "normal" PSA (<4 ng/ml) and non-suspicious digital rectal examination (DRE) remains to be determined. |
20860010 | Glycation sites in neoglycoglycoconjugates from the terminal monosaccharide antigen of the O-PS of Vibrio cholerae O1, serotype Ogawa, and BSA revealed by matrix-assisted laser desorption-ionization tandem mass spectrometry. | We present the MALDI-TOF/TOF-MS analyses of various hapten-bovine serum albumin (BSA) neoglycoconjugates obtained by squaric acid chemistry coupling of the spacer-equipped, terminal monosaccharide of the O-specific polysaccharide of Vibrio cholerae O1, serotype Ogawa, to BSA. These analyses allowed not only to calculate the molecular masses of the hapten-BSA neoglycoconjugates with different hapten-BSA ratios (4.3, 6.6 and 13.2) but, more importantly, also to localize the covalent linkages (conjugation sites) between the hapten and the carrier protein. Determination of the site of glycation was based parison of the MALDI-TOF/TOF-MS analysis of the peptides resulting from the digestion of BSA with similar data resulting from the digestion of BSA glycoconjugates, followed by sequencing by MALDI-TOF/TOF-MS/MS of the glycated peptides. The product-ion scans of the protonated molecules were carried out with a MALDI-TOF/TOF-MS/MS tandem mass spectrometer equipped with a high-collision energy cell. The high-energy collision-induced dissociation (CID) spectra afforded product ions formed by fragmentation of the carbohydrate hapten and amino acid sequences conjugated with fragments of the carbohydrate hapten. We were able to identify three conjugation sites on lysine residues (Lys235, Lys437 and Lys455). It was shown that these lysine residues are very reactive and bind lysine specific reagents. We presume that these Lys residues belong to those that are considered to be sterically more accessible on the surface of the tridimensional structure. The identification of the y-series product ions was very useful for the sequencing of various peptides. The series of a- and b-product ions confirmed the sequence of the conjugated peptides. |
20860011 | Truncated bFGF-mediated cationic liposomal paclitaxel for tumor-targeted drug delivery: improved pharmacokinetics and biodistribution in tumor-bearing mice. | Fibroblast growth factor receptors, overexpressed on the surface of a variety of tumor cells and on tumor neovasculature, are potential targets for tumor- and vascular-targeting therapy. The purpose of our present study was pare the pharmacokinetics and tissue distribution of a novel truncated basic fibroblast growth factor peptide-mediated cationic liposomal paclitaxel (tbFGF-LPs-PTX) with free paclitaxel (F-PTX) and cationic liposomal paclitaxel (LPs-PTX) in tumor-bearing mice. In plasma, tbFGF-LPs-PTX exhibited similar pharmacokinetic properties to LPs-PTX but different with F-PTX. The AUC(0→∞) values were about 1.38-fold and one pared with those of F-PTX and LPs-PTX, respectively. TbFGF-LPs-PTX showed significant difference in biodistribution characteristics and displayed high accumulation in tumor and spleen parison with other two formulations. The AUC(0→∞) values achieved, respectively, about 7.17-fold and 2.60-fold accumulation in tumor, and about 4.28-fold and 2.25-fold increase in pared with those of F-PTX and LPs-PTX. In contrast, the AUC(0→∞) values were much lower in pared with those of F-PTX and LPs-PTX. Our data indicated that tbFGF-LPs-PTX significantly increased the accumulation in tumor and prolonged the retention time, suggesting that it was a promise tumor-targeted delivery system and might provide a new treatment strategy for tumors. |
20860013 | Compositional studies of human RPE lipofuscin. | Age-related macular degeneration (AMD) is an ocular disease that causes visual loss and legal blindness in the elderly population. The etiology of AMD plex and may include genetic predispositions, accumulation of lipofuscin and drusen, local inflammation and neovascularization. The accumulation of lipofuscin has been shown to precede the death of photoreceptor cells and the deterioration of the RPE. As a result, the determination of the ponents of lipofuscin has been of major interest. One of ponents, previously identified as a bis-retinoid pound, is referred to as A2E. A2E has been characterized by mass spectrometry and is known to have a mass of 592 Da. Most remaining chromophores in RPE lipofuscin are structurally related to A2E as determined by their fragmentation pattern with losses of M ± 190, 174 and/or 150 Da. Analysis of lipofuscin from various donors indicated that the extracts consist of as many as 15 of these ponents, which are also observed to form spontaneously in vitro over extended periods of time. These consist of ca 90% of the ponents in RPE lipofuscin and correspond to derivatized A2E with discrete molecular weights of 800-900 m/z, 970-1080 m/z and above 1200 m/z regions. It was determined that these species are formed from self-reaction of A2E oxidation products or their reaction with A2E itself to form higher molecular weight products. The majority of modifications are much more hydrophobic than A2E and exhibit increasingly higher values of log P. This acts as a driving force for the sequestering of A2E into granules resulting in a itant diminution of its reactivity in vivo. |
20860012 | On variability in test results of current in vitro dissolution tests. | An analysis of theoretical cumulative mass dissolved-time profile curves represented by Weibull distributions serves to illustrate a dependency of variability in test results of current in vitro dissolution tests, on slope of a profile curve and amount of a cumulative time-shift, at any given point of a dissolution process. As a result of the dependency, a case of high variability can be shown to be an exaggerated reflection of variability in an initial delay in onset of dissolution of a product (due to, e.g., needed dissolution of a gelatin shell or coating, disintegration, and/or wetting etc.), rather than a true reflection of variability of the product in rate of dissolution (subsequent to, e.g., the dissolution of a gelatin shell or coating, disintegration, and/or wetting etc.). The high variability would not be of a clinical significance. |
20860014 | Exploring the mechanisms of intravesical electrical stimulation in the in vitro rat whole bladder after treatment with atropine, α,β-methylATP and tetrodotoxin. | In a previous study, we showed that the working mechanism of intravesical electrical stimulation (IVES) is probably mainly nerve mediated. But even after bladder decentralization, IVES can induce detrusor contraction. This study explores the effect of IVES in decentralized bladders and the importance of receptors in the bladder wall for a response on IVES. |
20860015 | Clinical relevance of urethral stents (Urospiral 2™) placement in patients with prostatic obstacle and concomitant high-risk surgical status or neurological diseases: a feasibility and safety study. | To review the indications and to assess the functional es after placement of a new temporary urethral stent (TUS) in men with lower urinary tract dysfunction. |
20860017 | Exercise improves bladder function in diabetic mice. | We determined the effect of exercise on bladder dysfunction and voiding frequency in db/db mice. |
20860016 | Intravesical immune suppression by liposomal tacrolimus in cyclophosphamide-induced inflammatory cystitis. | Potent immunosuppressive effect of tacrolimus has encouraged its topical application for achieving local anti-inflammatory effect. However, its poor aqueous solubility presents challenges in formulating patible instillations to justify the investigation of liposomes as vehicle for tacrolimus. |
20860018 | Type and severity of new-onset urinary incontinence in middle-aged women: the Hordaland Women's Cohort. | To determine the natural history of new-onset urinary incontinence by type and severity in middle-aged women. |
20860019 | Body mass index and blood pressure changes over the course of treatment of pediatric acute lymphoblastic leukemia. | Obesity and hypertension are reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, little is known about the trajectory of body mass index (BMI) and blood pressure over the course of ALL therapy. |
20860020 | Patient satisfaction with the benefits of overactive bladder treatment: exploration of influencing factors and development of a satisfaction assessment instrument. | Patient-reported e (PRO) instruments are useful for assessing treatment success in patients with overactive bladder (OAB). PROs such as the OAB Questionnaire (OAB-q) and Patient Perception of Bladder Condition (PPBC) focus more on OAB symptoms than satisfaction. We describe the development of the Patient Satisfaction with Treatment Benefit (PSTB) questionnaire, and examine the face, content and criterion validity of this tool in a study of darifenacin treatment in OAB patients who expressed dissatisfaction with prior antimuscarinic therapy. |
20860022 | The biosynthesis of branched dialkylpyrazines in myxobacteria. | The biosynthesis of the volatiles 2,5- and 2,6-diisopropylpyrazine (2 and 3, resp.) released by the myxobacteria Nannocystis exedens subsp. cinnabarina (Na c29) and Chondromyces crocatus (strains Cm c2 and Cm c5) was studied. Isotopically labeled precursors and proposed pathway intermediates were fed to agar plate cultures of the myxobacteria. Subsequently, the volatiles were collected by use of a closed loop stripping apparatus (CLSA), and incorporation into the pyrazines was followed by GC/MS analysis. [(2)H(8)]Valine was smoothly incorporated into both pyrazines clearly establishing their origin from the amino acid pool. The cyclic dipeptide valine anhydride (16)--a potential intermediate on the biosynthetic pathway to branched dialkylpyrazines--was synthesized containing (2)H(1) labels in specific positions. Feeding of [(2)H(16)]-16 and [(2)H(12)]-16 in both valine subunits mainly resulted in the formation of pyrazines derived from only one labeled amino acid, whereas only traces of the expected pyrazines with two labeled subunits were found. To investigate the origin of nitrogen in the pyrazines, a feeding experiment with [(15)N]valine was performed, resulting in the incorporation of the (15)N label. The results contradict a biosynthetic pathway via cyclic dipeptides, but rather point to a pathway on which valine is reduced to valine aldehyde. Its dimerization to 2,5-diisopropyldihydropyrazine 36 and subsequent oxidation results in 2. The proposed biosynthetic pathway neatly fits the results of earlier labeling studies and also explains the formation of the regioisomer 2,6-diisopropylpyrazine 3 by isomerization during the first condensation step of two molecules valine aldehyde. A general biosynthetic pathway to different classes of pyrazines is presented. |
20860023 | 2-azapurine nucleosides: synthesis, properties, and base pairing of oligonucleotides. | This review deals with 2-azapurine (imidazo[4,5-d] [1,2,3]triazine) nucleosides and closely related analogs. Different routes are described to yield the desired pounds, including a sequence of ring-opening and ring-closure reactions performed on purine nucleosides or direct glycosylation of a 2-azapurine nucleobase with a sugar halide. Further, physical and spectroscopic properties of 2-azapurine nucleosides are discussed, including fluorescence, (13)C-NMR data, single-crystal X-ray analyses, and conformation studies on pounds; new biological data are presented. The second part of this review is dedicated to oligonucleotides containing 2-azapurines, including building-block (phosphoramidite) preparation and their use in solid-phase oligonucleotide synthesis. Base-pairing properties of 2-azapurine nucleosides as surrogates of canonical constituents of DNA were evaluated. |
20860024 | An alternative standard for Trolox-equivalent antioxidant-capacity estimation based on thiol antioxidants. Comparative 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] decolorization and rotational viscometry study regarding hyaluronan degradation. | Comparison of the effectiveness of antioxidant activity of three pounds, D-penicillamine, reduced L-glutathione, and 1,4-dithioerythritol, expressed as a radical-scavenging capacity based on the two independent methods, namely a decolorization 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] assay and a rotational etry, is reported. Particular concern was focused on the testing of potential free-radical scavenging effects of thiols against hyaluronan degradation, induced by hydroxyl radicals. A promising, solvent-independent, antioxidative function of parable to that of a pound, Trolox(®), was confirmed by the 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] assay. The new potential antioxidant 1,4-dithioerythritol exhibited very good solubility in a variety of solvents (e.g., H(2)O, EtOH, and DMSO) and could be widely accepted and used as an effective antioxidant standard instead of a routinely used Trolox(®) on 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid] assay. |
20860026 | Volatile methyl esters of medium chain length from the bacterium Chitinophaga Fx7914. | The analysis of the volatiles released by the novel bacterial isolate Chitinophaga Fx7914 revealed the presence of ca. pounds including different methyl esters. These prise monomethyl- and dimethyl-branched, saturated, and unsaturated fatty acid methyl esters that have not been described as bacterial volatiles before. More than 30 esters of medium C-chain length were identified, which belong to five main classes, methyl (S)-2-methylalkanoates (class A), methyl (S)-2,(ω-1)-dimethylalkanoates (class B), methyl 2,(ω-2)-dimethylalkanoates (class C), methyl (E)-2-methylalk-2-enoates (class D), and methyl (E)-2,(ω-1)-dimethylalk-2-enoates (class E). The structures of pounds were verified by GC/MS analysis and synthesis of the pounds as methyl (S)-2-methyloctanoate (28), methyl (S)-2,7-dimethyloctanoate ((S)-43), methyl 2,6-dimethyloctanoate (49), methyl (E)-2-methylnon-2-enoate (20a), and methyl (E)-2,7-dimethyloct-2-enoate (41a). Furthermore, the natural saturated 2-methyl-branched methyl esters showed (S)-configuration as confirmed by GC/MS experiments using chiral phases. Additionally, the biosynthetic pathway leading to the methyl esters was investigated by feeding experiments with labeled precursors. The Me group at C(2) is introduced by propanoate incorporation, while the methyl ester is formed from the respective carboxylic acid by a methyltransferase using S-adenosylmethionine (SAM). |
20860027 | Early-season headspace volatiles from apple and their effect on the apple blossom weevil Anthonomus pomorum. | Apple volatiles emitted at early phenological stages are little investigated, although they may influence behavior of early-season pests. The apple blossom weevil Anthonomus pomorum is a herbivore pest of orchards in Europe. It colonizes apple trees in early season and oviposits into developing flower buds, often leading to economic damage. Using in situ radial diffusive sampling and thermal desorption, followed by GC/MS analysis, headspace volatiles from apple twigs with flower buds at three early phenological tree stages were identified and quantified. The volatile blend consisted of pounds for the first, and increased to pounds for the third phenological stage sampled. These blends included benzenoids, terpenes, and derivatives of fatty acids. A bined synthetic blend served as the odor source in a still-air dual-choice olfactometer bioassay, in which individual male and female weevils were tested. Results from this behavioral test document an attraction of both sexes to odors of their host plant, suggesting that apple volatiles emitted in early season serve as olfactory cues for host location of A. pomorum in the field. |
20860028 | A survey of phytotoxic microbial and plant metabolites as potential natural products for pest management. | Phytotoxic microbial metabolites produced by certain phytopathogenic fungi and bacteria, and a group of phytotoxic plant metabolites including Amaryllidacea alkaloids and some derivatives of pounds were evaluated for algicide, bactericide, insecticide, fungicide, and herbicide activities in order to discover pounds for potential use in the management and control of several important agricultural and household structural pests. Among the pounds evaluated: i) ophiobolin A was found to be the most promising for potential use as a selective algicide; ii) ungeremine was discovered to be bactericidal against certain species of fish pathogenic bacteria; iii) cycasin caused significant mortality in termites; iv) cavoxin, ophiobolin A, and sphaeropsidin A were most active towards species of plant pathogenic fungi; and v) lycorine and some of its analogues (1-O-acetyllycorine and lycorine chlorohydrate) were highly phytotoxic in the herbicide bioassay. Our results further demonstrated that plants and microbes can provide a diverse and natural source pounds with potential use as pesticides. |
20860030 | Bioactive triterpenoids from Kadsura heteroclita. | A phytochemical study of Kadsura heteroclita led to the isolation of eight triterpenoids, including two pounds, named kadheterilactone A (1) and kadheterilactone B (2), as well as six pounds, longipedlactone H (3), longipedlactone A (4), longipedlactone F (5), kadsuranic acid A (6), nigranoic acid (7), and schisandronic acid (8). Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. The cytotoxic activities of 1-8 were tested against several tumor cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium hydrobromide (MTT) assay in vitro. As a result, 4 and 5 turned out to be significantly cytotoxic against Hep-G2 and Bel-7402 tumor cell lines. pounds were also tested for inhibition on HIV-1 protease (PR) and reverse transcriptase (RT). Compounds 6 and 7 showed strong inhibition on HIV-1 PR, while 8 exhibited moderate activity, others were only weakly active. pounds were active against HIV-1 RT. |
20860029 | Phytochemical analysis and in vitro free-radical-scavenging activities of the essential oils from leaf and fruit of Melaleuca leucadendra L. | The phytochemical profile of Melaleuca leucadendra L. leaf and fruit oils from Cuba was investigated by GC and GC/MS. Forty-one and sixty-four pounds were identified and quantified, accounting for 99.2 and 99.5% of the leaf-oil and fruit-oil position, respectively. The ponents were 1,8-cineol (43.0%), viridiflorol (24.2%), α-terpineol (7.0%), α-pinene (5.3%), and limonene (4.8%) in the leaf oil, and viridiflorol (47.6%), globulol (5.8%), guaiol (5.3%), and α-pinene (4.5%) in the fruit oil. The antioxidant capacity of these essential oils was determined by three different in vitro assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, thiobarbituric acid reactive species (TBARS), and 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation), and significant activities were evidenced for all of them. |
20860032 | Anti-tumor-initiating effects of spiro-biflavonoids from Abies sachalinensis. | Cancer chemoprevention, the prevention of cancer by ingestion of chemical agents that reduce the risk of carcinogenesis, is one of the potent ways to reduce morbidity and mortality. We have been searching for cancer chemopreventive agents from the leaves and barks of coniferous trees that have been treated as waste in the forestry industry. We have previously reported the isolation of spiro-biflavonoids, named as abiesinols, and a neolignan from the MeOH extract of the bark of Abies sachalinensis. pounds were tested for their inhibitory effects on the activation of (±)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxyhex-3-enamide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. pounds tested exhibited potent inhibitory effects on NOR 1 activation. Furthermore, abiesinol A, bearing a spiro-biflavonoid skeleton, showed remarkable anti-tumor-initiating activity in the in vivo two-stage mouse skin carcinogenesis test using peroxynitrite (ONOO(-); PN) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. |
20860031 | Regulation of the 5-HT3A receptor-mediated current by alkyl 4-hydroxybenzoates isolated from the seeds of Nelumbo nucifera. | Four known alkyl 4-hydroxybenzoates, i.e., methyl 4-hydroxybenzoate (1), ethyl 4-hydroxybenzoate (2), propyl 4-hydroxybenzoate (3), and butyl 4-hydroxybenzoate (4), were isolated from the seeds of Nelumbo nucifera Gaertner (Nymphaeaceae) for the first time. The structures of the isolates were identified by 1D- and 2D-NMR spectroscopy parison with published values. pounds were evaluated for their effects on the 5-HT-stimulated inward current (I(5-HT)) mediated by the human 5-HT(3)A receptors expressed in Xenopus oocytes. Compounds 1 and 2 enhanced the I(5-HT), but 4 reduced it. These results indicate that 4 is an inhibitor of the 5-HT(3)A receptors expressed in Xenopus oocytes. |
20860033 | Volatile composition screening of Salix spp. nectar honey: benzenecarboxylic acids, norisoprenoids, terpenes, and others. | Salix spp. nectar honey volatiles of Croatian origin were analyzed by headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE), followed by gas chromatography and mass spectrometry (GC, GC/MS). Isolated volatiles were found in the honey headspace and extracts with almost exclusive distribution of several pounds (e.g., phenylacetic acid, pinocembrin, 8-hydroxy-4,7-dimethylcoumarin, and 3-hydroxy-trans-β-damascone in the extracts, or safranal and lilac alcohols in the headspace). Comparison with Croatian Salix spp. honeydew honey revealed similarities regarding distribution of important shikimate pathway derivatives (e.g., high percentage of phenylacetic acid) and several norisoprenoids (α-isophorone and 4-oxoisophorone). On the other hand, distinct features of this honey were occurrence pounds such as pinocembrin, 8-hydroxy-4,7-dimethylcoumarin, phenylacetonitrile, norisoprenoids (major ones: 3-hydroxy-trans-β-damascenone and trans-β-damascone), more pronounced variability of pounds, as well as the abundance of 3-methylpropanoic acid, 3-methylbutanoic acid, 2-methylpentanoic acid, and 3-methylpentan-1-ol. |
20860036 | Protracted postpartum urinary retention: the importance of early diagnosis and timely intervention. | To evaluate the prevalence and obstetric risk factors of protracted postpartum urinary retention, beyond the third postpartum day. |
20860038 | Phase 1 trial and pharmacokinetic study of the farnesyl transferase inhibitor tipifarnib in children and adolescents with refractory leukemias: a report from the Children's Oncology Group. | The objectives of this trial were to define the toxicity profile, dose, pharmacokinetics, and pharmacodynamics of the farnesyl transferase (FTase) inhibitor, tipifarnib, in children and adolescents with hematological malignancies. |
20860039 | The quinoxaline anti-tumor agent (R+)XK469 inhibits neuroblastoma tumor growth. | The quinoxaline anti-tumor agent (R+)XK469 mediates its effects by topoisomerase IIB inhibition. This report describes a 14-year old with relapsed neuroblastoma who experienced disease stabilization for 14 months while receiving (R+)XK469 monotherapy. Due to this favorable response, laboratory studies were undertaken to determine efficacy in the preclinical setting. (R+)XK469 inhibited proliferation, caused G(2) cell cycle arrest of neuroblastoma cells in vitro, and inhibited growth of neuroblastoma xenograft tumors. These preclinical results, coupled with the favorable clinical response, demonstrate that (R+)XK469 and similar anti-tumor agents may be effective in the treatment of high-risk neuroblastoma and warrant further testing. |
20860040 | Minor anomalies in children with hematological malignancies. | Despite the presence of reports on correlation between major congenital defects and cancer, very few studies have investigated the frequency of minor anomalies in childhood malignancy. The aim of this study was to determine the prevalence of minor anomalies in children with hematological malignancy. |
20860041 | Role of neoadjuvant chemotherapy in congenital intracranial haemangiopericytoma. | Infantile haemangiopericytoma of the CNS is a rare entity. We report the first case of a congenital haemangiopericytoma successfully treated by preoperative chemotherapy. The patient presented shortly after birth with the diagnosis of a haemangiopericytoma. As neurosurgery was too risky due to size, location and age of the patient an anthracycline-based chemotherapeutic regimen was applied and resulted in a significant decrease in tumour size, making a plete surgical resection possible. Chemotherapy may benefit patients with congenital haemangiopericytoma especially if the tumour cannot initially be treated plete neurosurgical resection. |
20860042 | Sequential acquisition of IgH and TCR rearrangements during the preleukemic phase of acute lymphoblastic leukemia in an adolescent patient. | Acute lymphoblastic leukemia (ALL) can be preceded by a prodromal phase of bone marrow failure. In serial trephine biopsies in a girl with acquired bone marrow hypoplasia, we have identified a monoclonal B-cell precursor population characterized by a clone-specific IgH-FR3 gene rearrangement. Progression to ALL more than 4 months later was panied by acquisition of an additional T-cell receptor rearrangement. Thus, hypoplastic pre- and overt leukemia share mon clonal origin. Prospective biobanking and extended molecular analysis can help to better understand the nature and sequence of genetic events during progression of a covert (pre)leukemic clone. |
20860043 | Malignant insulinoma in a child. | Insulinomas are rare tumors with an estimated incidence of one per 250,000 person-years. Most insulinomas are benign with less than 10% demonstrating malignant behavior, the vast majority of which occur in adults. A systemic review of the literature revealed only nine cases of malignant insulinomas occurring in children. Herein, we present a case of metastatic malignant insulinoma in a 12-year-old child. The occurrence of this diagnosis in a child, its unusual pattern of metastases and the challenging management of severe hypoglycemia make this case worth reporting. |
20860044 | Effect of cup inclination angle during microseparation and rim loading on the wear of BIOLOX® delta ceramic-on-ceramic total hip replacement. | Ceramic-on-ceramic (CoC) bearings in total hip replacements (THRs) have shown low wear volumes under standard gait in hip simulator studies. However, clinical reports have indicated variations in wear rates and formation of stripe-like wear area on the ceramic femoral heads. The aim of this study was to investigate the influence of cup inclination angle and microseparation on the wear of CoC bearings in THRs. The six station Leeds II Physiological Anatomical Joint Simulator was used to investigate the wear of 28 mm diameter alumina posite ceramic bearings (BIOLOX® delta). It was shown that increasing the cup inclination angle from 55° to 65° had no significant effect on the wear rate of BIOLOX® delta CoC under both standard gait and microseparation conditions in this in vitro study. Under standard gait conditions, the mean wear rate for both cup inclination angle conditions was very low at 0.05 mm(3)/million cycles. The introduction of microseparation to the standard gait cycle increased the mean wear rates to 0.13 mm(3)/million cycles for the cup inclination angle of 55° and 0.11 mm(3)/million cycles for that of 65°. The level of increased wear with microseparation was not dependent on cup angle. A stripe of wear on the head also formed, with corresponding superior rim wear on the cup. The wear rates obtained were pared to the HIPed third generation alumina ceramic (BIOLOX® forte) tested under the same adverse conditions (1.84 mm(3)/million cycles). BIOLOX® delta has shown lower wear than previous ceramic materials used in THR under adverse conditions. |
20860047 | Bioactive bone cement with a low content of titania particles without postsilanization: effect of filler content on osteoconductivity, mechanical properties, and handling characteristics. | In this study, we developed three types of polymethylmethacrylate posite cement with low contents of nonsilanized titania particles (5, 10, and 20 wt % TiO(2), respectively: designated T5, T10, and T20). The osteoconductivity, mechanical properties, and handling characteristics of these cements pared with those mercially available PMMA cement (PMMAc). The cement was inserted into rat tibiae and solidified in situ. After 6 and 12 weeks, tibiae were removed for evaluation of osteoconductivity using Stevenel's Blue and Van Gieson's picrofuchsin staining. The affinity indices reflecting the osteoconductivity of T10 and T20 were 33.4 ± 12.8 and 56.5 ± 14.1 at 6 weeks, and 67.0 ± 18.0 and 65.0 ± 51.7 at 12 weeks, respectively, and were significantly higher than for PMMAc (p < 0.01). pressive and flexural strengths of T5, T10, and T20 exceeded those of PMMAc, whereas the elasticity did not differ significantly. Scanning electron microscopy and energy-dispersive X-ray microanalysis showed that the micron-sized and spherical titania particles were well dispersed in T20 and were exposed on the surface of the cement that made direct contact with bone. These results show that T20 is a promising bioactive bone cement for use in prosthesis fixation. |
20860046 | Effects of immersion time and frequency of water exchange on durability of etch-and-rinse adhesive. | This study evaluated the immediate and long-term bond strength to dentin (microtensile bond strength, μTBS) and silver nitrate uptake (SNU) of a three- and two-step etch-and-rinse adhesive under different water immersion times and frequency of water exchange. The adhesives posite resin were applied according to the manufacturer's instructions in a flat occlusal demineralized dentin of 48 molars. Teeth were assigned to four groups of immersion time (immediate and 1, 3, and 6 months), sectioned to obtain resin-dentin beams, and then subdivided into three groups of water exchange (daily, weekly, and monthly) before being tested in tension. Two resin-dentin beams from each tooth were immersed in silver nitrate and analyzed by SEM. Significant difference in μTBS and SNU was detected for both adhesives (p ≤ 0.0001 for the cross-product interaction). For Adper Single Bond 2, the most pronounced reductions of μTBS were observed for the daily exchange groups in all times. For Adper Scotchbond Multi Purpose, 1-month immersion period was not capable to induce degradation of the dentin bonds, except when the water was exchanged daily. For both adhesives, all storage regimens showed increased SNU results only after 6-month water storage; this being more pronounced for daily water exchange groups. For both adhesives, the highest SNU was observed in the daily water exchange group. The daily water exchange is a fast and reliable in vitro aging method for testing the durability of the adhesive interface produced by adhesive systems. |
20860045 | Characterization of hydroxyapatite-perovskite (CaTiO3) composites: phase evaluation and cellular response. | In this study, an attempt was made to develop an understanding of the densification behavior, phase stability, and patibility property of HA-CaTiO(3) posite. posites with varying CaTiO(3) (40-80 wt %) content were sintered at temperatures ranging from 1200°C to 1500°C for 3-5 hr to establish optimum processing parameters. The phase analysis using spectral techniques indicate good patibility between HA and CaTiO(3). The microstructural observations reveal homogeneous distribution of finer CaTiO(3) phase (1-2 μm) along with coarser calcium phosphate phase. In vitro cell culture studies using L929 mouse fibroblast and SaOS2 human osteoblast cell lines provide clear evidence of cell adhesion, spreading, and proliferation as well as the formation of cellular bridges, and, hence, good in vitro patibility of the posite can be realized. Also, the number of viable cells was found to increase with incubation period, as revealed by statistical analysis of the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay data. |
20860048 | Endoscopic monitoring of infliximab therapy in Crohn's disease. | So far, infliximab (IFX) therapy for the treatment of Crohn's disease (CD) has generally been guided by clinical symptoms. Data on treatment response as ascertained by endoscopy in IFX therapy are scarce. The aims of this study were to measure the endoscopic response rate during IFX induction and maintenance therapy in luminal CD, and also evaluate the role of endoscopy in monitoring IFX therapy. |
20860052 | Racial and ethnic disparities in work-related injuries and socio-economic resources among nursing assistants employed in US nursing homes. | We aimed to estimate the proportion of nursing assistants (NAs) in the US with work-related injuries and insufficient socio-economic resources by race/ethnicity. |
20860053 | Improving the quality of industry and occupation data at a central cancer registry. | Central cancer registries are required to collect industry and occupation (I/O) information when available, but the data reported are often plete. |
20860054 | Confounders and confusion: Dealing with cancer cases of occupational origin. | The recognition of occupational cancers is often hampered by confusion between the individual determinants of the disease and effects at the group level. |
20860055 | Case-control study of male germ cell tumors nested in a cohort of car-manufacturing workers: Findings from the occupational history. | To examine whether the previously observed excess risk of male germ cell cancer in a cohort of car-manufacturing workers can be attributed to occupational activities inside and/or outside the car industry. |
20860057 | Imaging modalities to assess structural birth defects in mutant mouse models. | Assessment of structural birth defects (SBDs) in animal models usually entails conducting detailed necropsy for anatomical defects followed by histological analysis for tissue defects. Recent advances in new imaging technologies have provided the means for rapid phenotyping of SBDs, such as using ultra-high frequency ultrasound biomicroscopy, optical coherence tomography, micro-CT, and micro-MRI. These imaging modalities allow the detailed assessment of organ/tissue structure, and with ultrasound biomicroscopy, structure and function of the cardiovascular system also can be assessed noninvasively, allowing the longitudinal tracking of the fetus in utero. In this review, we briefly discuss the application of these state-of-the-art imaging technologies for phenotyping of SBDs in rodent embryos and fetuses, showing how these imaging modalities may be used for the detection of a wide variety of SBDs. |
20860056 | Cryopreservation of mammalian embryos: Advancement of putting life on hold. | Rodent transgenesis and human-assisted reproductive programs involve multistep handling of preimplantation embryos. The efficacy of production and quality of results from conventionally scheduled programs are limited by temporal constraints other than the quality and quantities of embryos per se. The emergence of vitrification, a water ice-free cryopreservation technique, as a reliable way to arrest further growth of preimplantation embryos, provides an option to eliminate the time constraint. In this article, current and potential applications of cryopreservation to facilitate laboratory animal experiments, colony management, and human-assisted reproductive programs are reviewed. Carrier devices developed for vitrification in the last two decades pared with an emphasis on their physical properties that infer cooling rate of samples and sterility assurance. Biological impacts of improved cryopreservation on preimplantation embryos are also discussed. |
20860050 | Nanotechnology and HIV: potential applications for treatment and prevention. | HIV/AIDS is a global pandemic and is the leading infectious cause of death among adults. Although antiretroviral (ARV) therapy has dramatically improved the quality of life and increased the life expectancy of those infected with HIV, life-long suppressive treatment is required and a cure for HIV infection remains elusive; frequency of dosing and drug toxicity as well as the development of viral resistance pose additional limitations. Furthermore, preventative measures such as a vaccine or microbicide are urgently needed to curb the rate of new infections. The capabilities inherent to nanotechnology hold much potential for impact in the field of HIV treatment and prevention. This article reviews the potential for the multidisciplinary field of nanotechnology to advance the fields of HIV treatment and prevention. |
20860051 | Revisiting an old friend: manganese-based MRI contrast agents. | Non-invasive cellular and molecular imaging techniques are emerging as a multidisciplinary field that offers promise in understanding ponents, processes, dynamics and therapies of disease at a molecular level. Magnetic resonance imaging (MRI) is an attractive technique due to the absence of radiation and high spatial resolution which makes it advantageous over techniques involving radioisotopes. Typically paramagnetic and superparamagnetic metals are used as contrast materials for MR based techniques. Gadolinium has been the predominant paramagnetic contrast metal until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF) in some patients with severe renal or kidney disease. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review manganese based contrast agent approaches will be presented with a particular emphasis on nanoparticulate agents. We have discussed both classically used small molecule based blood pool contrast agents and recently developed innovative nanoparticle-based strategies highlighting a number of successful molecular imaging examples. |