Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl− transport of mouse aortic smooth muscle cells

PubMed Central

Robert, Renaud; Norez, Caroline; Becq, Frédéric

2005-01-01

Chloride (Cl−) channels expressed in vascular smooth muscle cells (VSMC) are important to control membrane potential equilibrium, intracellular pH, cell volume maintenance, contraction, relaxation and proliferation. The present study was designed to compare the expression, regulation and function of CFTR Cl− channels in aortic VSMC from Cftr+/+ and Cftr−/− mice. Using an iodide efflux assay we demonstrated stimulation of CFTR by VIP, isoproterenol, cAMP agonists and other pharmacological activators in cultured VSMC from Cftr+/+. On the contrary, in cultured VSMC from Cftr−/− mice these agonists have no effect, showing that CFTR is the dominant Cl− channel involved in the response to cAMP mediators. Angiotensin II and the calcium ionophore A23187 stimulated Ca2+-dependent Cl− channels in VSMCs from both genotypes. CFTR was activated in myocytes maintained in medium containing either high potassium or 5-hydroxytryptamine (5-HT) and was inhibited by CFTRinh-172, glibenclamide and diphenylamine-2,2′-dicarboxylic acid (DPC). We also examined the mechanical properties of aortas. Arteries with or without endothelium from Cftr−/− mice became significantly more constricted (∼2-fold) than that of Cftr+/+ mice in response to vasoactive agents. Moreover, in precontracted arteries of Cftr+/+ mice, VIP and CFTR activators induced vasorelaxation that was altered in Cftr−/− mice. Our findings suggest a novel mechanism for regulation of the vascular tone by cAMP-dependent CFTR chloride channels in VSMC. To our knowledge this study is the first to report the phenotypic consequences of the loss of a Cl− channel on vascular reactivity. PMID:16081479

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Jin; Ye, Feng; Dan, Guorong

Nitrogen mustard (NM), a bifunctional alkylating agent (BAA), contains two alkyl arms and can act as a cross-linking bridge between DNA and protein to form a DNA-protein cross-link (DPC). O{sup 6}-methylguanine–DNA methyltransferase (MGMT), a DNA repair enzyme for alkyl adducts removal, is found to enhance cell sensitivity to BAAs and to promote damage, possibly due to its stable covalent cross-linking with DNA mediated by BAAs. To investigate MGMT-DNA cross-link (mDPC) formation and its possible dual roles in NM exposure, human bronchial epithelial cell line 16HBE was subjected to different concentrations of HN2, a kind of NM, and we found mDPCmore » was induced by HN2 in a concentration-dependent manner, but the mRNA and total protein of MGMT were suppressed. As early as 1 h after HN2 treatment, high mDPC was achieved and the level maintained for up to 24 h. Quick total DPC (tDPC) and γ-H2AX accumulation were observed. To evaluate the effect of newly predicted protease DVC1 on DPC cleavage, we applied siRNA of MGMT and DVC1, MG132 (proteasome inhibitor), and NMS-873 (p97 inhibitor) and found that proteolysis plays a role. DVC1 was proven to be more important in the cleavage of mDPC than tDPC in a p97-dependent manner. HN2 exposure induced DVC1 upregulation, which was at least partially contributed to MGMT cleavage by proteolysis because HN2-induced mDPC level and DNA damage was closely related with DVC1 expression. Homologous recombination (HR) was also activated. Our findings demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. Proteolysis, especially DVC1, plays a crucial role in mDPC repair. - Highlights: • Nitrogen mustard-induced MGMT-DNA cross-linking was detected in a living cell. • Concentration- and time-dependent manners of MGMT-DNA cross-linking were revealed. • Proteolysis played an important role in protein (MGMT)-DNA cross-linking repair. • DVC1 acts as a proteolytic enzyme in cross-linking repair in a p97-dependent manner.« less

Diphenylamine

Integrated Risk Information System (IRIS)

Integrated Risk Information System ( IRIS ) Chemical Assessment Summary U.S . Environmental Protection Agency National Center for Environmental Assessment This IRIS Summary has been removed from the IRIS database and is available for historical reference purposes . ( July 2016 ) Diphenylamine ; CASR

Photonic crystals on copolymer film for label-free detection of DNA hybridization.

PubMed

Su, Han; Cheng, Xin R; Endo, Tatsuro; Kerman, Kagan

2018-04-30

The presence of a single-nucleotide polymorphism in Apolipoprotein E4 gene is implicated with the increased risk of developing Alzheimer's disease (AD). In this study, detection of AD-related DNA oligonucleotide sequence associated with Apolipoprotein E4 gene sequence was achieved using localized-surface plasmon resonance (LSPR) on 2D-Photonic crystal (2D-PC) and Au-coated 2D-PC surfaces. 2D-PC surfaces were fabricated on a flexible copolymer film using nano-imprint lithography (NIL). The film surface was then coated with a dual-functionalized polymer to react with surface immobilized DNA probe. DNA hybridization was detected by monitoring the optical responses of either a Fresnel decrease in reflectance on 2D-PC surfaces or an increase in LSPR on Au-coated 2D-PC surfaces. The change in response due to DNA hybridization on the modified surfaces was also investigated using mismatched and non-complementary oligonucleotides sequences. The proof-of-concept results are promising towards the development of 2D-PC on copolymer film surfaces as miniaturized and wearable biosensors for various diagnostic and defense applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

PubMed Central

Bauer, K G; Kaik, B; Sertl, K; Kaik, G A

1993-01-01

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI. PMID:12959305

An integrated approach to care attracts people living with HIV who use illicit drugs in an urban centre with a concentrated HIV epidemic.

PubMed

Fernando, S; McNeil, R; Closson, K; Samji, H; Kirkland, S; Strike, C; Turje, R Baltzer; Zhang, W; Hogg, R S; Parashar, S

2016-11-22

People living with HIV (PLHIV) who are also marginalized by social and structural inequities often face barriers to accessing and adhering to HIV treatment and care. The Dr. Peter Centre (DPC) is a non-profit integrated care facility with a supervised injection room that serves PLHIV experiencing multiple barriers to social and health services in Vancouver, Canada. This study examines whether the DPC is successful in drawing in PLHIV with complex health issues, including addiction. Using data collected by the Longitudinal Investigations into Supportive and Ancillary health services (LISA) study from July 2007 to January 2010, linked with clinical variables available through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we identified DPC and non-DPC clients with a history of injection drug use. Bivariable and multivariable logistic regression analyses compared socio-demographic and clinical characteristics of DPC clients (n = 76) and non-DPC clients (n = 482) with a history of injection drug use. Of the 917 LISA participants included within this analysis, 100 (10.9%) reported being a DPC client, of which 76 reported a history of injection drug use. Adjusted results found that compared to non-DPC clients with a history of injection drug use, DPC-clients were more likely to be male (AOR: 4.18, 95% CI = 2.09-8.37); use supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79-5.61); to have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12-3.99); to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23-6.19); and to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI: 1.38-4.15). Our analyses suggest that the DPC operating care model engages PLHIV with complex care needs, highlighting that integrated care facilities are needed to support the multiple intersecting vulnerabilities faced by PLHIV with a history of injection drug use living within urban centres in North America and beyond.

In vitro assessment of the role of DpC in the treatment of head and neck squamous cell carcinoma.

PubMed

Xu, Ye-Xing; Zeng, Man-Li; Yu, Di; Ren, Jie; Li, Fen; Zheng, Anyuan; Wang, Yong-Ping; Chen, Chen; Tao, Ze-Zhang

2018-05-01

The present study aimed to investigate the antitumor efficacy of di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) and di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) on head and neck squamous cell carcinoma (HNSCC) cells. The proliferation and apoptosis of HNSCC cells treated with the iron chelators DpC and Dp44mT were detected. The mechanism of DpC-induced apoptosis on HNSCC cells was investigated. The human HNSCC cell lines FaDu, Cal-27 and SCC-9 were cultured in vitro and exposed to gradient concentrations of DpC and Dp44mT. A Cell Counting Kit-8 assay was used to detect the viability of FaDu, Cal-27, SCC-9 cells. Double staining with annexin V and propidium iodide was performed for the detection of the proportion of apoptotic FaDu, Cal-27 and SCC-9 cells following treatment. The nuclear damage to Cal-27 cells that were treated with DpC was detected by Hoechst staining. Finally, western blot analysis was used to detect the expression of proteins associated with the DNA damage pathway in Cal-27 cells that were treated with DpC. The CCK-8 assay showed that treatment with DpC and Dp44mT was able to markedly inhibit the viability of FaDu, Cal-27 and SCC-9 cells in a concentration-dependent manner. In comparison to Dp44mT, treatment with DpC exhibited a more effective inhibitory effect on the viability of HNSCC cells. The proportion of apoptotic cells detected by flow cytometry increased in a dose-dependent manner in all cell lines following DpC and Dp44mT treatment, with the proportion of apoptotic HNSCC cells induced by DpC treatment being significantly higher compared with Dp44mT (P<0.05). The results of Hoechst staining revealed that the nuclei of Cal-27 cells exhibited morphological changes in response to DpC treatment, including karyopyknosis and nuclear fragmentation. The expression of DNA damage-associated proteins, including phosphorylated (p)-serine-protein kinase ATM, p-serine/threonine-protein kinase Chk1 (p-Chk-1), p-serine/threonine-protein kinase ATR (p-ATR), p-Chk-2, poly (ADP-ribose) polymerase, p-histone H2AX, breast cancer type 1 susceptibility protein, p-tumor protein P53, increased with increasing concentration of DpC in Cal-27 cells. Treatment with DpC and Dp44mT markedly inhibited cell viability and increased the apoptotic rates in human HNSCC cells in a concentration-dependent manner. DpC exhibited a stronger antitumor effect compared with Dp44mT, potentially inducing the apoptosis of HNSCC cells via the upregulation of DNA damage repair-associated proteins.

Fundamental relationship between the noise properties of grating-based differential phase contrast CT and absorption CT: theoretical framework using a cascaded system model and experimental validation.

PubMed

Li, Ke; Bevins, Nicholas; Zambelli, Joseph; Chen, Guang-Hong

2013-02-01

Using a grating interferometer, a conventional x-ray cone beam computed tomography (CT) data acquisition system can be used to simultaneously generate both conventional absorption CT (ACT) and differential phase contrast CT (DPC-CT) images from a single data acquisition. Since the two CT images were extracted from the same set of x-ray projections, it is expected that intrinsic relationships exist between the noise properties of the two contrast mechanisms. The purpose of this paper is to investigate these relationships. First, a theoretical framework was developed using a cascaded system model analysis to investigate the relationship between the noise power spectra (NPS) of DPC-CT and ACT. Based on the derived analytical expressions of the NPS, the relationship between the spatial-frequency-dependent noise equivalent quanta (NEQ) of DPC-CT and ACT was derived. From these fundamental relationships, the NPS and NEQ of the DPC-CT system can be derived from the corresponding ACT system or vice versa. To validate these theoretical relationships, a benchtop cone beam DPC-CT/ACT system was used to experimentally measure the modulation transfer function (MTF) and NPS of both DPC-CT and ACT. The measured three-dimensional (3D) MTF and NPS were then combined to generate the corresponding 3D NEQ. Two fundamental relationships have been theoretically derived and experimentally validated for the NPS and NEQ of DPC-CT and ACT: (1) the 3D NPS of DPC-CT is quantitatively related to the corresponding 3D NPS of ACT by an inplane-only spatial-frequency-dependent factor 1∕f (2), the ratio of window functions applied to DPC-CT and ACT, and a numerical factor C(g) determined by the geometry and efficiency of the grating interferometer. Note that the frequency-dependent factor is independent of the frequency component f(z) perpendicular to the axial plane. (2) The 3D NEQ of DPC-CT is related to the corresponding 3D NEQ of ACT by an f (2) scaling factor and numerical factors that depend on both the attenuation and refraction properties of the image object, as well as C(g) and the MTF of the grating interferometer. The performance of a DPC-CT system is intrinsically related to the corresponding ACT system. As long as the NPS and NEQ of an ACT system is known, the corresponding NPS and NEQ of the DPC-CT system can be readily estimated using additional characteristics of the grating interferometer.

Dynamically programmable cache

NASA Astrophysics Data System (ADS)

Nakkar, Mouna; Harding, John A.; Schwartz, David A.; Franzon, Paul D.; Conte, Thomas

1998-10-01

Reconfigurable machines have recently been used as co- processors to accelerate the execution of certain algorithms or program subroutines. The problems with the above approach include high reconfiguration time and limited partial reconfiguration. By far the most critical problems are: (1) the small on-chip memory which results in slower execution time, and (2) small FPGA areas that cannot implement large subroutines. Dynamically Programmable Cache (DPC) is a novel architecture for embedded processors which offers solutions to the above problems. To solve memory access problems, DPC processors merge reconfigurable arrays with the data cache at various cache levels to create a multi-level reconfigurable machines. As a result DPC machines have both higher data accessibility and FPGA memory bandwidth. To solve the limited FPGA resource problem, DPC processors implemented multi-context switching (Virtualization) concept. Virtualization allows implementation of large subroutines with fewer FPGA cells. Additionally, DPC processors can parallelize the execution of several operations resulting in faster execution time. In this paper, the speedup improvement for DPC machines are shown to be 5X faster than an Altera FLEX10K FPGA chip and 2X faster than a Sun Ultral SPARC station for two different algorithms (convolution and motion estimation).

Synthesis, characterization, and nonlinear optical (NLO) properties of truxene-cored diphenylamine derivatives

NASA Astrophysics Data System (ADS)

Li, Fusheng; Zhao, Baodong; Chen, Yu; Zhang, Yufei; Wang, Tao; Xue, Song

2017-10-01

Three star-shaped compounds based on a truxene core (FS11, FS12 and FS13) were prepared. The truxene core is incorporating with asymmetric diphenylamines, including one phenyl of diphenylamine substituted by methoxy group and the other phenyl substituted by tolyl, fluorophenyl and phenylethynyl for FS11, FS12 and FS13, respectively. Their one-photon, two-photon absorption, geometric structures, electrochemical behavior and thermal properties were investigated. The absorption maxima of charge transfer band for FS11, FS12 and FS13 are 375 nm, 373 nm and 383 nm, and the corresponding molar extinction coefficients of FS11, FS12 and FS13 is 79,950 M- 1 cm- 1, 67,220 M- 1 cm- 1 and 108,780 M- 1 cm- 1. The ;pull-push; structure promotes charge transfer between asymmetric diphenylamine branches and the truxene core. Their two-photon absorbtion property is measured by two-photon induced fluorescence. The maximum two-photon cross-sections values of FS11, FS12 and FS13 are excited at 750 nm, which are 260 GM, 204GM and 367 GM, respectively.

Optimized light sharing for high-resolution TOF PET detector based on digital silicon photomultipliers.

PubMed

Marcinkowski, R; España, S; Van Holen, R; Vandenberghe, S

2014-12-07

The majority of current whole-body PET scanners are based on pixelated scintillator arrays with a transverse pixel size of 4 mm. However, recent studies have shown that decreasing the pixel size to 2 mm can significantly improve image spatial resolution. In this study, the performance of Digital Photon Counter (DPC) from Philips Digital Photon Counting (PDPC) was evaluated to determine their potential for high-resolution whole-body time of flight (TOF) PET scanners. Two detector configurations were evaluated. First, the DPC3200-44-22 DPC array was coupled to a LYSO block of 15 × 15 2 × 2 × 22 mm(3) pixels through a 1 mm thick light guide. Due to light sharing among the dies neighbour logic of the DPC was used. In a second setup the same DPC was coupled directly to a scalable 4 × 4 LYSO matrix of 1.9 × 1.9 × 22 mm(3) crystals with a dedicated reflector arrangement allowing for controlled light sharing patterns inside the matrix. With the first approach an average energy resolution of 14.5% and an average CRT of 376 ps were achieved. For the second configuration an average energy resolution of 11% and an average CRT of 295 ps were achieved. Our studies show that the DPC is a suitable photosensor for a high-resolution TOF-PET detector. The dedicated reflector arrangement allows one to achieve better performances than the light guide approach. The count loss, caused by dark counts, is overcome by fitting the matrix size to the size of DPC single die.

Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study.

PubMed

Ghosh, Anirban; Bhattacharyya, Dipita; Bhunia, Anirban

2018-02-01

In recent years, several studies based on the interaction of self-assembling short peptides derived from viroporins with model membranes, have improved our understanding of the molecular mechanism of corona virus (CoV) infection under physiological conditions. In this study, we have characterized the mechanism of membrane interaction of a short, 9-residue peptide TK9 (T 55 VYVYSRVK 63 ) that had been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied for its physical changes in the presence of both zwitterionic DPC and negatively charged SDS model membrane micelles, respectively, with the help of a battery of biophysical techniques including two-dimensional solution state NMR spectroscopy. Interestingly, in both micellar environments, TK9 adopted an alpha helical conformation; however, the helical propensities were much higher in the case of DPC compared to those of SDS micelle, suggesting that TK9 has more specificity towards eukaryotic cell membrane than the bacterial cell membrane. The orientation of the peptide TK9 also varies in the different micellar environments. The peptide's affinity was further manifested by its pronounced membrane disruption ability towards the mammalian compared to the bacterial membrane mimic. Collectively, the in-depth structural information on the interaction of TK9 with different membrane environments explains the host specificity and membrane orientation owing to subsequent membrane disruption implicated in the viral pathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of the per diem prospective payment system with DRG-like grouping system (DPC/PDPS) on resource usage and healthcare quality in Japan.

PubMed

Hamada, Hironori; Sekimoto, Miho; Imanaka, Yuichi

2012-10-01

In 2003, Japan introduced the prospective payment system (PPS) with diagnosis-related groups (DRG) rearranged grouping system called the diagnostic procedure combination/per-diem payment system (DPC/PDPS). Even after eight years, little is known about the effects of DPC/PDPS. The purpose of this study was to examine the effects of DPC/PDPS on resource usage and healthcare quality. Using 2001-2009 (fiscal year) administrative data of acute myocardial infarction patients, four indices, including inpatient total accumulated medical charges, length of stay (LOS), mortality rate, and readmission rate, were compared between patients reimbursed by DPC/PDPS or by fee-for-service. DPC/PDPS significantly reduced total accumulated medical charges by $1061 (95% confidence interval [CI], -2007, -116) and LOS by 2.29 days (95% CI, -3.71, -0.88) after risk adjustment. However, mortality rate (Odds ratio [OR], 0.94; 95% CI, 0.73, 1.21) was unchanged. Furthermore, DPC/PDPS increased the readmission rate (OR, 1.37; 95% CI, 1.03, 1.82). This study showed that DPC/PDPS was associated with reduced resource usage, but not improved healthcare quality, as with DRG/PPSs in other countries. To achieve successful healthcare reform, further discussion on additional motives will be required. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Evaluating the influence of fire history on dissolved pyrogenic C exported from coniferous and deciduous forest soils in northern Great Lakes Region

NASA Astrophysics Data System (ADS)

Santos, F.; Wagner, S.; Rothstein, D.; Miesel, J. R.; Jaffe, R.

2015-12-01

Pyrogenic carbon (PyC) is formed from the thermal decomposition of plant biomass and fossil fuels, and accounts for a significant portion of the dissolved organic matter pool in rivers worldwide. While PyC mobilization and leaching from fire-impacted terrestrial ecosystems are thought to be the primary source of dissolved PyC (DPC) in riverine environments, the influence of recent biomass burning on the fluxes of DPC leached from soils remains poorly quantified. Here we examined differences in DPC leaching fluxes between (1) red pine sites that experienced post-logging slash burning in the late 19th century, and (2) sugar maple sites that show no evidence of burning in the past 200 years. We collected spring snowmelt leachates from zero-tension lysimeters installed underneath O and E soil horizons of Spodosols in both red pine and sugar maple ecosystems. We quantified DPC in leachates by measuring Benzene Polycarboxylic Acids. We also determined DPC in leachates collected from lysimeters installed beneath B horizons in the red pine ecosystem. Average concentrations of DPC leached from O and E horizons in red pine and sugar maple sites were 1.22 ± 0.33 mg L-1 and 0.96 ±0.58 mg L-1, respectively. Although DPC concentrations in either the O or E horizon leachates did not differ between the two ecosystem types, the proportion of DPC in the dissolved organic C pool was 62% higher in red pine than in sugar maple in E horizon leachates. In red pine sites, DPC concentrations were significantly lower in the B horizon leachates than in the upper soil horizons leachates, likely due to DPC immobilization in the mineral subsoil. Our preliminary results showed that a single production of PyC was not the main source of DPC exported from soils, suggesting that DPC mobilized and released from the ecosystems studied here likely integrates PyC produced at a millennial time-scale in the Great Lakes Region.

Effects of pyridinium chlorochromate adulterant (urine luck) on testing for drugs of abuse and a method for quantitative detection of chromium (VI) in urine.

PubMed

Paul, B D; Martin, K K; Maguilo, J; Smith, M L

2000-01-01

Pyridinium chlorochromate (PCC) as an adulterant is popular for concealing drug-positive results. When 11-nor-delta9-THC-9-carboxylic acid (THC-acid) in urine was treated with 2 mmol/L of PCC (Cr6+ 104 microg/mL), 58-100% of the THC-acid was lost. The loss increased with decreasing pH and increasing reaction time (0-3 days). Free codeine and free morphine remained unaffected by PCC at pH within the physiological range of the urine (pH 5-7). At lower pH, the loss of free morphine varied from 0 to 100%. Amphetamine, methamphetamine, benzoylecgonine, and PCP remained unaffected by PCC when exposed to the oxidant for three days in urine pH of 3-7. Chromium (VI) from PCC in a urine solution was detected by a color reaction with 1,5-diphenylcarbazide (DPC). When the reagent was added to the urine, an immediate red-violet color appeared. The chromium-DPC complex showed a characteristic absorption peak at wavelength 544 nm with a shoulder at wavelength 575 nm. The ratio of absorption was used to identify the chromium compound. The concentration of chromium (VI) was determined by measuring absorption at wavelength 544 nm and was linear over 0.5-20 microg/mL. The limit of detection of the procedure was 0.37 microg/mL.

Anatomical background noise power spectrum in differential phase contrast breast images

NASA Astrophysics Data System (ADS)

Garrett, John; Ge, Yongshuai; Li, Ke; Chen, Guang-Hong

2015-03-01

In x-ray breast imaging, the anatomical noise background of the breast has a significant impact on the detection of lesions and other features of interest. This anatomical noise is typically characterized by a parameter, β, which describes a power law dependence of anatomical noise on spatial frequency (the shape of the anatomical noise power spectrum). Large values of β have been shown to reduce human detection performance, and in conventional mammography typical values of β are around 3.2. Recently, x-ray differential phase contrast (DPC) and the associated dark field imaging methods have received considerable attention as possible supplements to absorption imaging for breast cancer diagnosis. However, the impact of these additional contrast mechanisms on lesion detection is not yet well understood. In order to better understand the utility of these new methods, we measured the β indices for absorption, DPC, and dark field images in 15 cadaver breast specimens using a benchtop DPC imaging system. We found that the measured β value for absorption was consistent with the literature for mammographic acquisitions (β = 3.61±0.49), but that both DPC and dark field images had much lower values of β (β = 2.54±0.75 for DPC and β = 1.44±0.49 for dark field). In addition, visual inspection showed greatly reduced anatomical background in both DPC and dark field images. These promising results suggest that DPC and dark field imaging may help provide improved lesion detection in breast imaging, particularly for those patients with dense breasts, in whom anatomical noise is a major limiting factor in identifying malignancies.

The expression and underlying angiogenesis effect of DPC4 and VEGF on the progression of cervical carcinoma

PubMed Central

A, Yanni; Li, Ying; Zhao, Shuping

2018-01-01

The present study aimed to investigate the expression and roles of deleted in pancreatic carcinoma locus 4 (DPC4) and vascular endothelial growth factor (VEGF) in the development of cervical carcinoma. A total of 115 patients aged between 25 and 60 years were involved, including 19 cervical inflammation, 35 cervical intraepithelial neoplasia (CIN), and 61 cervical squamous-cell carcinoma (CSCC). The protein expression rates of DPC4 and VEGF in all samples were detected using immunohistochemistry. The protein levels of DPC4 and VEGF in CSCC samples were measured using ELISA. Microvessel density (MVD) of each CSCC sample was measured according to the Winder method. Association analysis between DPC4, VEGF and thrombospondin-1 (TSP-1) was conducted using Spearman's correlations. The negative expression rate of DPC4 [DPC4 (−)] and positive expression rate of VEGF [VEGF (+)] of the CSCC group were significantly higher compared with that in the cervical inflammation and CIN groups (P<0.05). In the CSCC group, the protein level of DPC4 decreased, while the VEGF level increased significantly compared with the healthy control group (P<0.05). The MVD in the DPC4 (−), VEGF (+) and TSP-1 (−) groups was significantly increased compared with that of the DPC4 (+), VEGF (−), and TSP-1 (+) groups (P<0.05). The expression of DPC4 was negatively associated with VEGF and TSP-1 (P<0.01). These results suggest that DPC4, VEGF and TSP-1 are involved in the carcinogenesis of cervical carcinoma by inducing angiogenesis. In addition, the loss of DPC4 induces angiogenesis through increasing VEGF. Thus, VEGF may be a target gene regulated by DPC4. PMID:29434970

The expression and underlying angiogenesis effect of DPC4 and VEGF on the progression of cervical carcinoma.

PubMed

A, Yanni; Li, Ying; Zhao, Shuping

2018-02-01

The present study aimed to investigate the expression and roles of deleted in pancreatic carcinoma locus 4 (DPC4) and vascular endothelial growth factor (VEGF) in the development of cervical carcinoma. A total of 115 patients aged between 25 and 60 years were involved, including 19 cervical inflammation, 35 cervical intraepithelial neoplasia (CIN), and 61 cervical squamous-cell carcinoma (CSCC). The protein expression rates of DPC4 and VEGF in all samples were detected using immunohistochemistry. The protein levels of DPC4 and VEGF in CSCC samples were measured using ELISA. Microvessel density (MVD) of each CSCC sample was measured according to the Winder method. Association analysis between DPC4, VEGF and thrombospondin-1 (TSP-1) was conducted using Spearman's correlations. The negative expression rate of DPC4 [DPC4 (-)] and positive expression rate of VEGF [VEGF (+)] of the CSCC group were significantly higher compared with that in the cervical inflammation and CIN groups (P<0.05). In the CSCC group, the protein level of DPC4 decreased, while the VEGF level increased significantly compared with the healthy control group (P<0.05). The MVD in the DPC4 (-), VEGF (+) and TSP-1 (-) groups was significantly increased compared with that of the DPC4 (+), VEGF (-), and TSP-1 (+) groups (P<0.05). The expression of DPC4 was negatively associated with VEGF and TSP-1 (P<0.01). These results suggest that DPC4, VEGF and TSP-1 are involved in the carcinogenesis of cervical carcinoma by inducing angiogenesis. In addition, the loss of DPC4 induces angiogenesis through increasing VEGF. Thus, VEGF may be a target gene regulated by DPC4.

Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases.

PubMed

Yoo, Chae Hwa; Na, Hee-Jun; Lee, Dong-Seol; Heo, Soon Chul; An, Yuri; Cha, Junghwa; Choi, Chulhee; Kim, Jae Ho; Park, Joo-Cheol; Cho, Yee Sook

2013-11-01

Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies. Under conventional differentiation conditions, 2F hDPC-hiPSCs showed higher differentiation efficiency, compared to hiPSCs from other cell types, into multipotent CD34(+) EPCs (2F-hEPCs) capable to differentiate into functional endothelial and smooth muscle cells. The angiogenic and neovasculogenic activities of 2F-hEPCs were confirmed using a Matrigel plug assay in mice. In addition, the therapeutic effects of 2F-hEPC transplantation were confirmed in mouse models of hind-limb ischemia and myocardial infarction. Importantly, 2F-EPCs effectively integrated into newly formed vascular structures and enhanced neovascularization via likely both direct and indirect paracrine mechanisms. 2F hDPC-hiPSCs have a robust capability for the generation of angiogenic and vasculogenic EPCs, representing a strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model.

PubMed

Marques, T M; Patterson, E; Wall, R; O'Sullivan, O; Fitzgerald, G F; Cotter, P D; Dinan, T G; Cryan, J F; Ross, R P; Stanton, C

2016-06-01

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~10(9)microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~10(9) L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

Effect of neutral endopeptidase inhibition on substance-P-induced increase in short-circuit current of canine cultured tracheal epithelium.

PubMed

Tamaoki, J; Sakai, N; Isono, K; Kanemura, T; Chiyotani, A; Yamauchi, F; Takizawa, T; Konno, K

1991-01-01

We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.

Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.

PubMed

Lachgar, S; Charveron, M; Gall, Y; Bonafe, J L

1998-03-01

The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed. This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA. Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation. These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.

The effect of long-term administered CRAC channels blocker on the functions of respiratory epithelium in guinea pig allergic asthma model.

PubMed

Sutovska, Martina; Kocmalova, Michaela; Joskova, Marta; Adamkov, Marian; Franova, Sona

2015-04-01

Previously, therapeutic potency of CRAC channels blocker was evidenced as a significant decrease in airway smooth muscle hyperreactivity, antitussive and anti-inflammatory effects. The major role of the respiratory epithelium in asthma pathogenesis was highlighted only recently and CRAC channels were proposed as the most significant route of Ca2+ entry into epithelial cells. The aim of the study was to analyse the impact of long-term administered CRAC channels blocker on airway epithelium, e.g. cytokine production and ciliary beat frequency (CBF) using an animal model of allergic asthma. Ovalbumin-induced allergic airway inflammation of guinea pigs was followed by long-term (14 days lasted) therapy by CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA). The influence of long-term therapy on cytokines (IL-4, IL-5 and IL-13) in BALF and in plasma, immunohistochemical staining of pulmonary tissue (c-Fos positivity) and CBF in vitro were used for analysis. Decrease in cytokine levels and in c-Fos positivity confirmed an anti-inflammatory effect of long-term administered FPCA. Cytokine levels in BALF and distribution of c-Fos positivity suggested that FPCA was a more potent inhibitor of respiratory epithelium secretory functions than budesonide. FPCA and budesonide reduced CBF only insignificantly. All findings supported CRAC channels as promising target in the new strategy of antiasthmatic treatment.

Vaccine Efficacy Against a New Avian Influenza (H9N2) Field Isolate from the Middle East (Serology and Challenge Studies).

PubMed

Gharaibeh, Saad; Amareen, Shadi

2016-05-01

Avian influenza subtype H9N2 is endemic in many countries in the Middle East. The reported prevalence of infection was variable between countries and ranged from 28.7% in Tunisia to 71% in Jordan. Several commercial killed whole-virus vaccine products are used as monovalent or bivalent mixed with Newcastle disease virus. Recently, we have noticed that many of the vaccinated broiler flocks did not show a production advantage over nonvaccinated flocks in the field. A new avian influenza field virus (H9N2) was isolated from these vaccinated and infected broiler flocks in 2013. This virus had 89.1% similarity of its hemagglutinin (HA) gene to the classical virus used for manufacturing the classical vaccine. Inactivated autogenous vaccine was manufactured from this new field isolate to investigate its serological response and protection in specific-pathogen-free (SPF) and breeder-male chickens compared to the classical vaccine. Oropharyngeal virus shedding of vaccinated breeder-male chickens was evaluated at 3, 9, 10, and 14 days postchallenge (DPC). Percentage of chickens shedding the virus at 3 DPC was 64%, 50%, and 64% in the classical vaccine group, autogenous vaccine group, and the control challenged group, respectively. At 7 DPC percentage of virus shedding was 42%, 7%, and 64% in the classical vaccine group, autogenous vaccine group, and the control challenged group, respectively. At 10 DPC only 9% of classical vaccine group was shedding the virus and there was no virus shedding in any of the groups at 14 DPC. There was statistical significance difference (P < 0.05) in shedding only at 7 DPC between the autogenous vaccine group and the other two groups. At 42 days of age (14 DPC), average body weight was 2.720, 2.745, 2.290, and 2.760 kg for the classical vaccine group, autogenous vaccine group, control challenged group, and control unchallenged group, respectively. Only the control challenged group had significantly (P < 0.05) lower average body weight. In another experiment, vaccinated SPF chicks had hemagglutination inhibition (HI) geometric mean titers (GMTs), with classical antigen, of 8.7 and 3.1 log 2 for classical and autogenous vaccine groups, respectively. When the autogenous antigen was used for HI, GMTs were 6.0 and 8.1 log 2, respectively. Both vaccines protected against body weight suppression after challenge. However, autogenous vaccine elicited significantly higher HI titer and reduced viral shedding at 7 DPC. In conclusion, it is important to revise the vaccine virus strains used in each region to protect against and control infection from new field strains. Further field experiments are needed to demonstrate the efficacy of new vaccines under field conditions.

Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics.

PubMed

Amos, W B; Reichelt, S; Cattermole, D M; Laufer, J

2003-05-01

In this paper, differential phase imaging (DPC) with transmitted light is implemented by adding a suitable detection system to a standard commercially available scanning confocal microscope. DPC, a long-established method in scanning optical microscopy, depends on detecting the intensity difference between opposite halves or quadrants of a split photodiode detector placed in an aperture plane. Here, DPC is compared with scanned differential interference contrast (DIC) using a variety of biological specimens and objective lenses of high numerical aperture. While DPC and DIC images are generally similar, DPC seems to have a greater depth of field. DPC has several advantages over DIC. These include low cost (no polarizing or strain-free optics are required), absence of a double scanning spot, electronically variable direction of shading and the ability to image specimens in plastic dishes where birefringence prevents the use of DIC. DPC is also here found to need 20 times less laser power at the specimen than DIC.

MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Jun; Zhang, Shuyu; Zhou, Yingqi

2011-03-25

Research highlights: {yields} We identify miR-421 as a novel potential regulator of DPC4/Smad4. {yields} The expression levels of miR-421 and DPC4/Smad4 are inversely correlated in human clinical specimens of pancreatic cancer. {yields} Overexpression of miR-421 represses the reporter activities driven by the 3'-UTR of DPC4/Smad4 and DPC4/Smad4 protein level in pancreatic cancer cell. {yields} Ectopic expression of miR-421 promotes the proliferation and colony formation of pancreatic cancer cell. -- Abstract: MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progressionmore » of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.« less

GDPC: Gravitation-based Density Peaks Clustering algorithm

NASA Astrophysics Data System (ADS)

Jiang, Jianhua; Hao, Dehao; Chen, Yujun; Parmar, Milan; Li, Keqin

2018-07-01

The Density Peaks Clustering algorithm, which we refer to as DPC, is a novel and efficient density-based clustering approach, and it is published in Science in 2014. The DPC has advantages of discovering clusters with varying sizes and varying densities, but has some limitations of detecting the number of clusters and identifying anomalies. We develop an enhanced algorithm with an alternative decision graph based on gravitation theory and nearby distance to identify centroids and anomalies accurately. We apply our method to some UCI and synthetic data sets. We report comparative clustering performances using F-Measure and 2-dimensional vision. We also compare our method to other clustering algorithms, such as K-Means, Affinity Propagation (AP) and DPC. We present F-Measure scores and clustering accuracies of our GDPC algorithm compared to K-Means, AP and DPC on different data sets. We show that the GDPC has the superior performance in its capability of: (1) detecting the number of clusters obviously; (2) aggregating clusters with varying sizes, varying densities efficiently; (3) identifying anomalies accurately.

New spectrophotometric methods for the determinations of hydrogen sulfide present in the samples of lake water, industrial effluents, tender coconut, sugarcane juice and egg

NASA Astrophysics Data System (ADS)

Shyla, B.; Nagendrappa, G.

2012-10-01

The new methods are working on the principle that iron(III) is reduced to iron(II) by hydrogen sulfide, catechol and p-toluidine the system 1/hydrogen sulfide the system 2, in acidic medium followed by the reduced iron forming complex with 1,10-phenanthroline with λmax 510 nm. The other two methods are based on redox reactions between electrolytically generated manganese(III) sulfate taken in excess and hydrogen sulfide followed by the unreacted oxidant oxidizing diphenylamine λmax 570 the system 3/barium diphenylamine sulphonate λmax 540 nm, the system 4. The increase/decrease in the color intensity of the dye products of the systems 1 and 2 or 3 and 4 are proportional to the concentration of hydrogen sulfide with its quantification range 0.035-1.40 μg ml-1/0.14-1.40 μg ml-1.

A New Method to Develop Human Dental Pulp Cells and Platelet-rich Fibrin Complex.

PubMed

He, Xuan; Chen, Wen-Xia; Ban, Guifei; Wei, Wei; Zhou, Jun; Chen, Wen-Jin; Li, Xian-Yu

2016-11-01

Platelet-rich fibrin (PRF) has been used as a scaffold material in various tissue regeneration studies. In the previous methods to combine seed cells with PRF, the structure of PRF was damaged, and the manipulation time in vitro was also increased. The objective of this in vitro study was to explore an appropriate method to develop a PRF-human dental pulp cell (hDPC) complex to maintain PRF structure integrity and to find out the most efficient part of PRF. The PRF-hDPC complex was developed at 3 different time points during PRF preparation: (1) the before centrifugation (BC) group, the hDPC suspension was added to the venous blood before blood centrifugation; (2) the immediately after centrifugation (IAC) group, the hDPC suspension was added immediately after blood centrifugation; (3) the after centrifugation (AC) group, the hDPC suspension was added 10 minutes after blood centrifugation; and (4) the control group, PRF without hDPC suspension. The prepared PRF-hDPC complexes were cultured for 7 days. The samples were fixed for histologic, immunohistochemistry, and scanning electron microscopic evaluation. Real-time polymerase chain reaction was performed to evaluate messenger RNA expression of alkaline phosphatase and dentin sialophosphoprotein. Enzyme-linked immunosorbent assay quantification for growth factors was performed within the different parts of the PRF. Histologic, immunohistochemistry, and scanning electron microscopic results revealed that hDPCs were only found in the BC group and exhibited favorable proliferation. Real-time polymerase chain reaction revealed that alkaline phosphatase and dentin sialophosphoprotein expression increased in the cultured PRF-hDPC complex. The lower part of the PRF released the maximum quantity of growth factors. Our new method to develop a PRF-hDPCs complex maintained PRF structure integrity. The hDPCs were distributed in the buffy coat, which might be the most efficient part of PRF. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

R-spondin1 and FOXL2 act into two distinct cellular types during goat ovarian differentiation.

PubMed

Kocer, Ayhan; Pinheiro, Iris; Pannetier, Maëlle; Renault, Lauriane; Parma, Pietro; Radi, Orietta; Kim, Kyung-Ah; Camerino, Giovanna; Pailhoux, Eric

2008-04-02

Up to now, two loci have been involved in XX sex-reversal in mammals following loss-of-function mutations, PIS (Polled Intersex Syndrome) in goats and R-spondin1 (RSPO1) in humans. Here, we analyze the possible interaction between these two factors during goat gonad development. Furthermore, since functional redundancy between different R-spondins may influence gonad development, we also studied the expression patterns of RSPO2, 3 and 4. Similarly to the mouse, RSPO1 shows a sex-dimorphic expression pattern during goat gonad development with higher levels in the ovaries. Interestingly, the PIS mutation does not seem to influence its level of expression. Moreover, using an RSPO1 specific antibody, the RSPO1 protein was localized in the cortical area of early differentiating ovaries (36 and 40 dpc). This cortical area contains the majority of germ cell that are surrounded by FOXL2 negative somatic cells. At latter stages (50 and 60 dpc) RSPO1 protein remains specifically localized on the germ cell membranes. Interestingly, a time-specific relocation of RSPO1 on the germ cell membrane was noticed, moving from a uniform distribution at 40 dpc to a punctuated staining before and during meiosis (50 and 60 dpc respectively). Interestingly, also RSPO2 and RSPO4 show a sex-dimorphic expression pattern with higher levels in the ovaries. Although RSPO4 was found to be faintly and belatedly expressed, the expression of RSPO2 increases at the crucial 36 dpc stage, as does that of FOXL2. Importantly, RSPO2 expression appears dramatically decreased in XX PIS-/- gonads at all three tested stages (36, 40 and 50 dpc). During goat ovarian development, the pattern of expression of RSPO1 is in agreement with its possible anti-testis function but is not influenced by the PIS mutation. Moreover, our data suggest that RSPO1 may be associated with germ cell development and meiosis. Interestingly, another RSPO gene, RSPO2 shows a sex-dimorphic pattern of expression that is dramatically influenced by the PIS mutation.

R-spondin1 and FOXL2 act into two distinct cellular types during goat ovarian differentiation

PubMed Central

Kocer, Ayhan; Pinheiro, Iris; Pannetier, Maëlle; Renault, Lauriane; Parma, Pietro; Radi, Orietta; Kim, Kyung-Ah; Camerino, Giovanna; Pailhoux, Eric

2008-01-01

Background Up to now, two loci have been involved in XX sex-reversal in mammals following loss-of-function mutations, PIS (Polled Intersex Syndrome) in goats and R-spondin1 (RSPO1) in humans. Here, we analyze the possible interaction between these two factors during goat gonad development. Furthermore, since functional redundancy between different R-spondins may influence gonad development, we also studied the expression patterns of RSPO2, 3 and 4. Results Similarly to the mouse, RSPO1 shows a sex-dimorphic expression pattern during goat gonad development with higher levels in the ovaries. Interestingly, the PIS mutation does not seem to influence its level of expression. Moreover, using an RSPO1 specific antibody, the RSPO1 protein was localized in the cortical area of early differentiating ovaries (36 and 40 dpc). This cortical area contains the majority of germ cell that are surrounded by FOXL2 negative somatic cells. At latter stages (50 and 60 dpc) RSPO1 protein remains specifically localized on the germ cell membranes. Interestingly, a time-specific relocation of RSPO1 on the germ cell membrane was noticed, moving from a uniform distribution at 40 dpc to a punctuated staining before and during meiosis (50 and 60 dpc respectively). Interestingly, also RSPO2 and RSPO4 show a sex-dimorphic expression pattern with higher levels in the ovaries. Although RSPO4 was found to be faintly and belatedly expressed, the expression of RSPO2 increases at the crucial 36 dpc stage, as does that of FOXL2. Importantly, RSPO2 expression appears dramatically decreased in XX PIS-/- gonads at all three tested stages (36, 40 and 50 dpc). Conclusion During goat ovarian development, the pattern of expression of RSPO1 is in agreement with its possible anti-testis function but is not influenced by the PIS mutation. Moreover, our data suggest that RSPO1 may be associated with germ cell development and meiosis. Interestingly, another RSPO gene, RSPO2 shows a sex-dimorphic pattern of expression that is dramatically influenced by the PIS mutation. PMID:18384673

EZH2 Impairs Human Dental Pulp Cell Mineralization via the Wnt/β-Catenin Pathway.

PubMed

Li, B; Yu, F; Wu, F; Hui, T; A, P; Liao, X; Yin, B; Wang, C; Ye, L

2018-05-01

The enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of PRC2 (polycomb repressor complex 2). It mediates gene silencing via methyltransferase activity and is involved in the determination of cell lineage. However, the function of EZH2 and the underlying mechanisms by which it affects the differentiation of human dental pulp cell (hDPC) have remained underexplored. In this research, we found that EZH2 expression decreased during the mineralization of hDPCs, with attenuated H3K27me3 (trimethylation on lysine 27 in histone H3). Overexpression of EZH2 impaired the odontogenic differentiation of hDPCs, while EZH2 without methyltransferase activity mutation (mutation of suppressed variegation of 3 to 9, enhancer of zeste and trithorax domain, EZH2ΔSET) did not display this phenotype. In addition, siRNA knockdown studies showed that EZH2 negatively modulated hDPC differentiation in vitro and inhibited mineralized nodule formation in transplanted β-tricalcium phosphate / hDPC composites. To further investigate the underlying mechanisms, we explored the Wnt/β-catenin signaling pathway in view of the fact that previous research had documented the essential role that it plays during hDPC mineralization, as well as its links to EZH2 in other cells. We demonstrated for the first time that EZH2 depletion activated the Wnt/β-catenin signaling pathway and enhanced the accumulation of β-catenin in hDPCs. Chromatin immunoprecipitation analysis suggested that these effects are attributable to the level of the EZH2-regulated H3K27me3 on the β-catenin promoter. We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. Suppression of EZH2 could promote hDPC mineralization by epigenetically regulating the expression of β-catenin and activating the Wnt canonical signaling pathway.

Generating chimeric mice from embryonic stem cells via vial coculturing or hypertonic microinjection.

PubMed

Lee, Kun-Hsiung

2014-01-01

The generation of a fertile embryonic stem cell (ESC)-derived or F0 (100 % coat color chimerism) mice is the final criterion in proving that the ESC is truly pluripotent. Many methods have been developed to produce chimeric mice. To date, the most popular methods for generating chimeric embryos is well sandwich aggregation between zona pellucida (ZP) removed (denuded) 2.5-day post-coitum (dpc) embryos and ESC clumps, or direct microinjection of ESCs into the cavity (blastocoel) of 3.5-dpc blastocysts. However, due to systemic limitations and the disadvantages of conventional microinjection, aggregation, and coculturing, two novel methods (vial coculturing and hypertonic microinjection) were developed in recent years at my laboratory.Coculturing 2.5-dpc denuded embryos with ESCs in 1.7-mL vials for ~3 h generates chimeras that have significantly high levels of chimerism (including 100 % coat color chimerism) and germline transmission. This method has significantly fewer instrumental and technological limitations than existing methods, and is an efficient, simple, inexpensive, and reproducible method for "mass production" of chimeric embryos. For laboratories without a microinjection system, this is the method of choice for generating chimeric embryos. Microinjecting ESCs into a subzonal space of 2.5-dpc embryos can generate germline-transmitted chimeras including 100 % coat color chimerism. However, this method is adopted rarely due to the very small and tight space between ZP and blastomeres. Using a laser pulse or Piezo-driven instrument/device to help introduce ESCs into the subzonal space of 2.5-dpc embryos demonstrates the superior efficiency in generating ESC-derived (F0) chimeras. Unfortunately, due to the need for an expensive instrument/device and extra fine skill, not many studies have used either method. Recently, ESCs injected into the large subzonal space of 2.5-dpc embryos in an injection medium containing 0.2-0.3 M sucrose very efficiently generated viable, healthy, and fertile chimeric mice with 100 % coat color chimerism.Both vial coculture and hypertonic microinjection methods are useful and effective alternatives for producing germline chimeric or F0 mice efficiently and reliably. Furthermore, both novel methods are also good for induced pluripotent stem cells (iPSCs) to generate chimeric embryos.

Bi-anchoring organic sensitizers of type D-(π-A)2 comprising thiophene-2-acetonitrile as π-spacer and malonic acid as electron acceptor for dye sensitized solar cell applications

NASA Astrophysics Data System (ADS)

Reddy, Gachumale Saritha; Ramkumar, Sekar; Asiri, Abdullah M.; Anandan, Sambandam

2015-06-01

Two new bi-anchoring organic sensitizers of type D-(π-A)2 comprising the identical π-spacer (thiophene-2-acetonitrile) and electron acceptor (malonic acid) but different aryl amine as electron donors (diphenylamine and carbazole) were synthesized, characterized and fabricated metal free dye-sensitized solar cell devices. The intra molecular charge transfer property and electrochemical property of these dyes were investigated by molecular absorption, emission, cyclic voltammetric experiments and in addition, quantum chemical calculation studies were performed to provide sufficient driving force for the electron injection into the conduction band of TiO2 which leads to efficient charge collection. Among the fabricated devices, carbazole based device exhibits high current conversion efficiency (η = 4.7%) with a short circuit current density (JSC) 15.3 mA/cm2, an open circuit photo voltage (VOC) of 0.59 V and a fill factor of 0.44 under AM 1.5 illumination (85 mW/cm2) compared to diphenylamine based device.

False-positive result when a diphenylcarbazide spot test is used on trivalent chromium-passivated zinc surfaces.

PubMed

Reveko, Valeriia; Lampert, Felix; Din, Rameez U; Thyssen, Jacob P; Møller, Per

2018-05-01

A colorimetric 1,5-diphenylcarbazide (DPC)-based spot test can be used to identify hexavalent chromium on various metallic and leather surfaces. DPC testing on trivalent chromium-passivated zinc surfaces has unexpectedly given positive results in some cases, apparently indicating the presence of hexavalent chromium; however, the presence of hexavalent chromium has never been confirmed with more sensitive and accurate test methods. To examine the presence of hexavalent chromium on trivalent chromium-passivated zinc surfaces with a DPC-based spot test. A colorimetric DPC spot test was used for the initial detection of hexavalent chromium on new and 1-year-aged trivalent chromium-passivated zinc surfaces. Then, X-ray photoelectron spectroscopy (XPS) was performed for all samples. The DPC spot test indicated the presence of hexavalent chromium in aged, but not new, trivalent chromium passivation on zinc; however, subsequent analysis by XPS could not confirm the presence of chromium in a hexavalent state. Unintended oxidation of DPC induced by atmospheric corrosion is suggested as a possible reason for the false-positive reaction of the DPC test on a trivalent chromium-passivated zinc surface. Further validation of the use of the DPC test for chromium-containing metallic surfaces is required. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Characterization of imaging performance in differential phase contrast CT compared with the conventional CT: Spectrum of noise equivalent quanta NEQ(k)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang Xiangyang; Yang Yi; Tang Shaojie

Purpose: Differential phase contrast CT (DPC-CT) is emerging as a new technology to improve the contrast sensitivity of conventional attenuation-based CT. The noise equivalent quanta as a function over spatial frequency, i.e., the spectrum of noise equivalent quanta NEQ(k), is a decisive indicator of the signal and noise transfer properties of an imaging system. In this work, we derive the functional form of NEQ(k) in DPC-CT. Via system modeling, analysis, and computer simulation, we evaluate and verify the derived NEQ(k) and compare it with that of the conventional attenuation-based CT. Methods: The DPC-CT is implemented with x-ray tube and gratings.more » The x-ray propagation and data acquisition are modeled and simulated through Fresnel and Fourier analysis. A monochromatic x-ray source (30 keV) is assumed to exclude any system imperfection and interference caused by scatter and beam hardening, while a 360 Degree-Sign full scan is carried out in data acquisition to avoid any weighting scheme that may disrupt noise randomness. Adequate upsampling is implemented to simulate the x-ray beam's propagation through the gratings G{sub 1} and G{sub 2} with periods 8 and 4 {mu}m, respectively, while the intergrating distance is 193.6 mm (1/16 of the Talbot distance). The dimensions of the detector cell for data acquisition are 32 Multiplication-Sign 32, 64 Multiplication-Sign 64, 96 Multiplication-Sign 96, and 128 Multiplication-Sign 128 {mu}m{sup 2}, respectively, corresponding to a 40.96 Multiplication-Sign 40.96 mm{sup 2} field of view in data acquisition. An air phantom is employed to obtain the noise power spectrum NPS(k), spectrum of noise equivalent quanta NEQ(k), and detective quantum efficiency DQE(k). A cylindrical water phantom at 5.1 mm diameter and complex refraction coefficient n= 1 -{delta}+i{beta}= 1 -2.5604 Multiplication-Sign 10{sup -7}+i1.2353 Multiplication-Sign 10{sup -10} is placed in air to measure the edge transfer function, line spread function and then modulation transfer function MTF(k), of both DPC-CT and the conventional attenuation-based CT. The x-ray flux is set at 5 Multiplication-Sign 10{sup 6} photon/cm{sup 2} per projection and observes the Poisson distribution, which is consistent with that of a micro-CT for preclinical applications. Approximately 360 regions, each at 128 Multiplication-Sign 128 matrix, are used to calculate the NPS(k) via 2D Fourier transform, in which adequate zero padding is carried out to avoid aliasing in noise. Results: The preliminary data show that the DPC-CT possesses a signal transfer property [MTF(k)] comparable to that of the conventional attenuation-based CT. Meanwhile, though there exists a radical difference in their noise power spectrum NPS(k) (trait 1/|k| in DPC-CT but |k| in the conventional attenuation-based CT) the NEQ(k) and DQE(k) of DPC-CT and the conventional attenuation-based CT are in principle identical. Conclusions: Under the framework of ideal observer study, the joint signal and noise transfer property NEQ(k) and detective quantum efficiency DQE(k) of DPC-CT are essentially the same as those of the conventional attenuation-based CT. The findings reported in this paper may provide insightful guidelines on the research, development, and performance optimization of DPC-CT for extensive preclinical and clinical applications in the future.« less

New spectrophotometric methods for the determinations of hydrogen sulfide present in the samples of lake water, industrial effluents, tender coconut, sugarcane juice and egg.

PubMed

Shyla, B; Nagendrappa, G

2012-10-01

The new methods are working on the principle that iron(III) is reduced to iron(II) by hydrogen sulfide, catechol and p-toluidine the system 1/hydrogen sulfide the system 2, in acidic medium followed by the reduced iron forming complex with 1,10-phenanthroline with λ(max) 510 nm. The other two methods are based on redox reactions between electrolytically generated manganese(III) sulfate taken in excess and hydrogen sulfide followed by the unreacted oxidant oxidizing diphenylamine λ(max) 570 the system 3/barium diphenylamine sulphonate λ(max) 540 nm, the system 4. The increase/decrease in the color intensity of the dye products of the systems 1 and 2 or 3 and 4 are proportional to the concentration of hydrogen sulfide with its quantification range 0.035-1.40 μg ml(-1)/0.14-1.40 μg ml(-1). Copyright © 2012 Elsevier B.V. All rights reserved.

Computer-Aided Synthesis and Design of Monolithic Microwave GaAs MESFET Amplifiers.

DTIC Science & Technology

1983-08-01

increased by iDPC until the limiting value for realizability is encountered (at about 0.023 in this example). (Note that the DPC axis in Figure 2.6(b...warranted on how best to use it in designing circuits. ------- ---- 26 Rou Mf) 50.0 40.0 30.0 ii I I I I I I IDPC 0.0002 0.0006 0.001 0.004 0.008...ORDER GS =6 INPUT 0.401 MIL=O0 NETWORK iDPC z 3.0 6W: 8.25 -9.50 8.944 0.091 (b) -.jRIP a0.092 dB 4TH ORDER 0.034 0.504 GS :6 INPUT MIL:0 NETWORK 0-BW

CD and 31P NMR studies of tachykinin and MSH neuropeptides in SDS and DPC micelles

NASA Astrophysics Data System (ADS)

Schneider, Sydney C.; Brown, Taylor C.; Gonzalez, Javier D.; Levonyak, Nicholas S.; Rush, Lydia A.; Cremeens, Matthew E.

2016-02-01

Secondary structural characteristics of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), α-melanocyte stimulating hormone peptide (α-MSH), γ1-MSH, γ2-MSH, and melittin were evaluated with circular dichroism in phosphite buffer, DPC micelles, and SDS micelles. CD spectral properties of γ1-MSH and γ2-MSH as well as 31P NMR of DPC micelles with all the peptides are reported for the first time. Although, a trend in the neuropeptide/micelle CD data appears to show increased α-helix content for the tachykinin peptides (SP, NKA, NKB) and increased β-sheet content for the MSH peptides (α-MSH, γ1-MSH, γ2-MSH) with increasing peptide charge, the lack of perturbed 31P NMR signals for all neuropeptides could suggest that the reported antimicrobial activity of SP and α-MSH might not be related to a membrane disruption mode of action.

Spectroscopic Investigation of the Electrosynthesis of Diphenyl Carbonate from CO and Phenol on Gold Electrodes

PubMed Central

2018-01-01

In this work, we study the synthesis of diphenyl carbonate (DPC) from phenol and CO on gold electrodes studied by means of in situ Fourier transform infrared spectroscopy (FTIR). The results show that, on gold electrodes, the formation of DPC is observed at potentials as low as 0.4 V vs Ag/AgCl, together with the formation of dimethyl carbonate (DMC) from the carbonylation of methanol that was used as a solvent. The spectroelectrochemical results also suggest that the formation of DPC occurs via the replacement of the methoxy groups from DMC with phenoxy groups from phenol and not directly by the carbonylation of phenol. Although this transesterification process is known to occur with heterogeneous catalysts, it has not been reported under electrochemical conditions. These are interesting findings, since the direct DPC production by carbonylation of phenol to DPC is usually performed with Pd-based catalysts. With this reaction scheme of transesterification happening under electrochemical conditions, other non-Pd catalysts could be used as well for one-step DPC production from phenol and CO. These findings give important mechanistic insights into this reaction and open up possibilities to an alternative process for the production of DPC. PMID:29657886

High Cost of Hospitalization for Colonic Diverticular Bleeding Depended on Repeated Bleeding and Blood Transfusion: Analysis with Diagnosis Procedure Combination Data in Japan.

PubMed

Ito, Yoichiro; Sakata, Yasuhisa; Yoshida, Hisako; Nonaka, Sayuri; Fujii, Susumu; Tanaka, Yuichiro; Shirai, Shimpei; Takeshita, Eri; Akutagawa, Takashi; Kawakubo, Hiroharu; Yamamoto, Koji; Tsuruoka, Nanae; Shimoda, Ryo; Iwakiri, Ryuichi; Fujimoto, Kazuma

2017-01-01

Bleeding from a colonic diverticulum is serious in aged patients. The aim of this study was to determine the risk factors for high-cost hospitalization of colonic diverticular bleeding using the diagnosis procedure combination (DPC) data. From January 2009 to December 2015, 78 patients with colonic diverticular bleeding were identified by DPC data in Saga Medical School Hospital. All patients underwent colonic endoscopy within 3 days. The patients were divided into 2 groups: the low-cost group (DPC cost of <500,000 yen) and the high-cost group (DPC cost of >500,000 yen). Univariate analysis revealed that aging, hypertension, rebleeding, a low hemoglobin concentration at admission, and blood transfusion were risk factors for high hospitalization cost. Multivariate analysis revealed that rebleeding (OR 5.3; 95% CI 1.3-21.3; p = 0.017) and blood transfusion (OR 3.8; 95% CI 1.01-14.2; p = 0.048) were definite risk factors for high hospitalization cost. Rebleeding and blood transfusion were related to high hospitalization cost for colonic diverticular bleeding. © 2017 S. Karger AG, Basel.

Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stingele, Julian; Bellelli, Roberto; Alte, Ferdinand

Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled bymore » several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define a DNA switch triggering its protease activity, a ubiquitin switch controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage. Our data also provide a molecular explanation on how SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.« less

Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN

DOE PAGES

Stingele, Julian; Bellelli, Roberto; Alte, Ferdinand; ...

2016-10-27

Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled bymore » several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define a DNA switch triggering its protease activity, a ubiquitin switch controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage. Our data also provide a molecular explanation on how SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.« less

Correction of data truncation artifacts in differential phase contrast (DPC) tomosynthesis imaging

NASA Astrophysics Data System (ADS)

Garrett, John; Ge, Yongshuai; Li, Ke; Chen, Guang-Hong

2015-10-01

The use of grating based Talbot-Lau interferometry permits the acquisition of differential phase contrast (DPC) imaging with a conventional medical x-ray source and detector. However, due to the limited area of the gratings, limited area of the detector, or both, data truncation image artifacts are often observed in tomographic DPC acquisitions and reconstructions, such as tomosynthesis (limited-angle tomography). When data are truncated in the conventional x-ray absorption tomosynthesis imaging, a variety of methods have been developed to mitigate the truncation artifacts. However, the same strategies used to mitigate absorption truncation artifacts do not yield satisfactory reconstruction results in DPC tomosynthesis reconstruction. In this work, several new methods have been proposed to mitigate data truncation artifacts in a DPC tomosynthesis system. The proposed methods have been validated using experimental data of a mammography accreditation phantom, a bovine udder, as well as several human cadaver breast specimens using a bench-top DPC imaging system at our facility.

Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression.

PubMed

Crane, Christopher H; Varadhachary, Gauri R; Yordy, John S; Staerkel, Gregg A; Javle, Milind M; Safran, Howard; Haque, Waqar; Hobbs, Bridgett D; Krishnan, Sunil; Fleming, Jason B; Das, Prajnan; Lee, Jeffrey E; Abbruzzese, James L; Wolff, Robert A

2011-08-01

This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.

Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium.

PubMed

Medeiros, M G; Rodrigues, A S; Batoréu, M C; Laires, A; Rueff, J; Zhitkovich, A

2003-01-01

DNA-protein crosslinks (DPC) are a promising biomarker of exposure to hexavalent chromium, a known human carcinogen. Although trivalent chromium is considered to have much lower toxicity, the risk involved in chronic exposure is uncertain. DPC may be a useful tool in clarifying this risk, by signaling an exposure of body tissues to biologically active forms of chromium. DPC quantification was carried out in lymphocytes of a group of tannery workers exposed to trivalent chromium, a small group of manual metal arc stainless steel welders exposed to hexavalent chromium and a control group. This biomarker was compared with the frequency of micronuclei in cytokinesis blocked peripheral lymphocytes as a biomarker of cytogenetic lesions and total plasma and urine chromium levels as an index of exposure. The results indicate a significant increase in the formation of DPC in tannery workers compared with controls (0.88 +/- 0.19 versus 0.57 +/- 0.21%, P < 0.001, Mann-Whitney test) and an even higher level of DPC in welders (2.22 +/- 1.12%, P = 0.03). Tanners showed a significant increase in micronucleated cells compared with controls (6.35 +/- 2.94 versus 3.58 +/- 1.69 per thousand, P < 0.01), whereas in welders this increase was not significant (5.40 +/- 1.67 per thousand ). Urinary chromium was increased in both groups, with a greater increase observed in tanners compared with controls (2.63 +/- 1.62 versus 0.70 +/- 0.38 microg/g creatinine, P < 0.001) than in welders (1.90 +/- 0.37 microg/g creatinine, P < 0.005). Plasma chromium was also increased in both groups (tanners 2.43 +/- 2.11 microg/l, P < 0.001, welders 1.55 +/- 0.67 microg/l, P < 0.005 versus controls 0.41 +/- 0.11 microg/l). In summary, chronic occupational exposure to trivalent chromium can lead to a detectable increase in lymphocyte DNA damage which correlates with a significant exposure of the cells to the metal.

A mechanism for overcoming P-glycoprotein-mediated drug resistance: novel combination therapy that releases stored doxorubicin from lysosomes via lysosomal permeabilization using Dp44mT or DpC.

PubMed

Seebacher, Nicole A; Richardson, Des R; Jansson, Patric J

2016-12-01

The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers. Thus, the combination of these agents should be considered as an effective rationalized therapy for potently treating advanced and resistant tumors that are often heterogeneous in terms of Pgp-expression. These studies demonstrate that both Dp44mT and DpC are transported into lysosomes via Pgp transport activity, where they induce lysosomal-membrane permeabilization to release DOX trapped within lysosomes. This novel strategy of loading lysosomes with DOX, followed by permeabilization with Dp44mT or DpC, results in the relocalization of stored DOX from its lysosomal 'safe house' to its nuclear targets, markedly enhancing cellular toxicity against resistant tumor cells. Notably, the combination of Dp44mT or DpC with DOX showed a very high level of synergism in multiple Pgp-expressing cell types, for example, cervical, breast and colorectal cancer cells. These studies revealed that the level of drug synergy was proportional to Pgp activity. Interestingly, synergism was ablated by inhibiting Pgp using the pharmacological inhibitor, Elacridar, or by inhibiting Pgp-expression using Pgp-silencing, demonstrating the importance of Pgp in the synergistic interaction. Furthermore, lysosomal-membrane stabilization inhibited the relocalization of DOX from lysosomes to the nucleus upon combination with Dp44mT or DpC, preventing synergism. This latter observation demonstrated the importance of lysosomal-membrane permeabilization to the synergistic interaction between these agents. The synergistic and potent anti-tumor efficacy observed between DOX and thiosemicarbazones represents a promising treatment combination for advanced cancers, which are heterogeneous and composed of non-Pgp- and Pgp-expressing tumor cells.

Single-shot quantitative phase microscopy with color-multiplexed differential phase contrast (cDPC).

PubMed

Phillips, Zachary F; Chen, Michael; Waller, Laura

2017-01-01

We present a new technique for quantitative phase and amplitude microscopy from a single color image with coded illumination. Our system consists of a commercial brightfield microscope with one hardware modification-an inexpensive 3D printed condenser insert. The method, color-multiplexed Differential Phase Contrast (cDPC), is a single-shot variant of Differential Phase Contrast (DPC), which recovers the phase of a sample from images with asymmetric illumination. We employ partially coherent illumination to achieve resolution corresponding to 2× the objective NA. Quantitative phase can then be used to synthesize DIC and phase contrast images or extract shape and density. We demonstrate amplitude and phase recovery at camera-limited frame rates (50 fps) for various in vitro cell samples and c. elegans in a micro-fluidic channel.

DPC 681 and DPC 684: Potent, Selective Inhibitors of Human Immunodeficiency Virus Protease Active against Clinically Relevant Mutant Variants

PubMed Central

Kaltenbach, Robert F.; Trainor, George; Getman, Daniel; Harris, Greg; Garber, Sena; Cordova, Beverly; Bacheler, Lee; Jeffrey, Susan; Logue, Kelly; Cawood, Pamela; Klabe, Ronald; Diamond, Sharon; Davies, Marc; Saye, Joanne; Jona, Janan; Erickson-Viitanen, Susan

2001-01-01

Human immunodeficiency virus (HIV) protease inhibitors (PIs) are important components of many highly active antiretroviral therapy regimens. However, development of phenotypic and/or genotypic resistance can occur, including cross-resistance to other PIs. Development of resistance takes place because trough levels of free drug are inadequate to suppress preexisting resistant mutant variants and/or to inhibit de novo-generated resistant mutant variants. There is thus a need for new PIs, which are more potent against mutant variants of HIV and show higher levels of free drug at the trough. We have optimized a series of substituted sulfonamides and evaluated the inhibitors against laboratory strains and clinical isolates of HIV type 1 (HIV-1), including viruses with mutations in the protease gene. In addition, serum protein binding was determined to estimate total drug requirements for 90% suppression of virus replication (plasma IC90). Two compounds resulting from our studies, designated DPC 681 and DPC 684, are potent and selective inhibitors of HIV protease with IC90s for wild-type HIV-1 of 4 to 40 nM. DPC 681 and DPC 684 showed no loss in potency toward recombinant mutant HIVs with the D30N mutation and a fivefold or smaller loss in potency toward mutant variants with three to five amino acid substitutions. A panel of chimeric viruses constructed from clinical samples from patients who failed PI-containing regimens and containing 5 to 11 mutations, including positions 10, 32, 46, 47, 50, 54, 63, 71, 82, 84, and 90 had mean IC50 values of <20 nM for DPC 681 and DPC 681, respectively. In contrast, marketed PIs had mean IC50 values ranging from 200 nM (amprenavir) to >900 nM (nelfinavir). PMID:11600351

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease.

PubMed

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-03-28

To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats. Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.

Methods for the Syntheses of Mono-, Di-, Tri- and Tetranitro Derivatives of Diphenylamine.

DTIC Science & Technology

1986-01-01

condensation of the relevant nitroaniline (2- and 4- isomers) with bromobenzene (solvent) or nitroacetanilide (3- isomer) with bromobenzene in...Goldberg(ref.6) gave the 3- isomer. WSRL-0436-TR - 8 - A well agitated mixture of 3- nitroacetanilide (12.0 g, 0.067 mol), bromobenzene (21.0 g, 0.134

In situ UV-visible spectroelectrochemical evidences for conducting copolymer formation between diphenylamine and m-methoxyaniline.

PubMed

Thanneermalai, M; Jeyaraman, T; Sivakumar, C; Gopalan, A; Vasudevan, T; Wen, T C

2003-07-01

Electrochemical copolymerization of diphenylamine (DPA) with m-methoxy aniline (MA) was carried out in 4 M H(2)SO(4) by cyclic voltammetry (CV). Cyclic voltammograms (CVs) of the copolymer films were recorded in monomer-free background electrolyte. In situ sepectroelectrochemical studies were carried out on an optically transparent electrode (Indium tin oxide (ITO) coated glass) in 4 M H(2)SO(4) for different feed ratios of the comonomers. Constant potential and potential sweep methods were employed for performing polymerization. UV-visible absorption spectra were collected continuously and concurrently during the copolymerization in both the cases. The results from constant potential electropolymerisation indicated the formation of an intermediate with an absorption peak at 576 nm. Derivative cyclic voltabsorptogram (DCVA) was deduced from the results of cyclic spectrovoltammetry. The DCVA derived at 576 nm confirms the intermediates formed during the electrochemical copolymerization. The compositional changes of the two monomers in the copolymers with changes in feed composition of two monomers as predicted from in situ spectro electrochemical studies are evident from elemental analysis. A plausible copolymerization mechanism is suggested.

Development of hospital data warehouse for cost analysis of DPC based on medical costs.

PubMed

Muranaga, F; Kumamoto, I; Uto, Y

2007-01-01

To develop a data warehouse system for cost analysis, based on the categories of the diagnosis procedure combination (DPC) system, in which medical costs were estimated by DPC category and factors influencing the balance between costs and fees. We developed a data warehouse system for cost analysis using data from the hospital central data warehouse system. The balance data of patients who were discharged from Kagoshima University Hospital from April 2003 to March 2005 were determined in terms of medical procedure, cost per day and patient admission in order to conduct a drill-down analysis. To evaluate this system, we analyzed cash flow by DPC category of patients who were categorized as having malignant tumors and whose DPC category was reevaluated in 2004. The percentages of medical expenses were highest in patients with acute leukemia, non-Hodgkin's lymphoma, and particularly in patients with malignant tumors of the liver and intrahepatic bile duct. Imaging tests degraded the percentages of medical expenses in Kagoshima University Hospital. These results suggested that cost analysis by patient is important for hospital administration in the inclusive evaluation system using a case-mix index such as DPC.

Comparative Analyses by Sequencing of Transcriptomes during Skeletal Muscle Development between Pig Breeds Differing in Muscle Growth Rate and Fatness

PubMed Central

Li, Anning; Gong, Wen; Xiao, Shuqi; Zhang, Yue; Qin, Limei; Niu, Yuna; Guo, Yunxue; Liu, Xiaohong; Cong, Peiqing; He, Zuyong; Wang, Chong; Li, Jiaqi; Chen, Yaosheng

2011-01-01

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement. The raw data have been submitted to Gene Expression Omnibus (GEO) under series GSE25406. PMID:21637832

Comparative analyses by sequencing of transcriptomes during skeletal muscle development between pig breeds differing in muscle growth rate and fatness.

PubMed

Zhao, Xiao; Mo, Delin; Li, Anning; Gong, Wen; Xiao, Shuqi; Zhang, Yue; Qin, Limei; Niu, Yuna; Guo, Yunxue; Liu, Xiaohong; Cong, Peiqing; He, Zuyong; Wang, Chong; Li, Jiaqi; Chen, Yaosheng

2011-01-01

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement. The raw data have been submitted to Gene Expression Omnibus (GEO) under series GSE25406.

Synthesis and optoelectronic properties of dodecyl substituted diphenylamine and pyridine based conjugated molecule

NASA Astrophysics Data System (ADS)

Priyanka, V.; Vijai Anand, A. S.; Mahesh, K.; Karpagam, S.

2017-11-01

The new donor-acceptor type conjugated moiety, namely 3-([4-(2-Cyano-2pyridine-2yl-vinyl)-phenyl]-dodecyl-amino)-phenyl)-2-pyridine-2-yl-acrylonitrile (DPA-PA) has been synthesized according to the Knoevenagel condensation. Here dodecyloxy diphenylamine moiety acts as an electron donor and cyano-pyridyl moiety acts as an electron acceptor. These moieties are recently showing great interest in optoelectronic applications. The structure of the DPA-PA was confirmed by FT-IR, 1H NMR. The final product showed great solubility in common organic solvents such as toluene, tetrahydrofuran, ethyl acetate, dichloromethane, chloroform etc due to the dodecyl chain. The absorption maximum of DPA-PA appeared at 433 nm in chloroform solution. The optical band gap is 2.2 eV calculated from thin film absorption edge (550 nm). The photoluminescence spectra exhibited a maximum peak at 513 nm with greenish fluorescence in chloroform solution and at 541 nm as the thin film state. The emission spectra of thin film state are 28 nm red shifted with broadening peak. The lower electrochemical band gap 1.55 eV was observed by cyclic voltammetry. This type of low band gap materials has much attention for their various potential applications in optoelectronic devices.

Novel roles of ascorbate in plants: induction of cytosolic Ca2+ signals and efflux from cells via anion channels.

PubMed

Makavitskaya, M; Svistunenko, D; Navaselsky, I; Hryvusevich, P; Mackievic, V; Rabadanova, C; Tyutereva, E; Samokhina, V; Straltsova, D; Sokolik, A; Voitsekhovskaja, O; Demidchik, V

2018-02-17

Ascorbate is not often considered as a signalling molecule in plants. This study demonstrates that, in Arabidopsis roots, exogenous L-ascorbic acid triggers a transient increase of the cytosolic free calcium activity ([Ca2+]cyt.) that is central to plant signalling. Exogenous copper and iron stimulates the ascorbate-induced [Ca2+]cyt. elevation while cation channel blockers, free radical scavengers, low extracellular [Ca2+], transition metal chelators and removal of the cell wall inhibit this reaction. These data show that apoplastic redox-active transition metals are involved in the ascorbate-induced [Ca2+]cyt. elevation. Exogenous ascorbate also induces a moderate increase in programmed cell death symptoms in intact roots, but it does not activate Ca2+ influx currents in patch-clamped root protoplasts. Intriguingly, the replacement of gluconate with ascorbate in the patch-clamp pipette reveales a large ascorbate efflux current, which shows sensitivity to the anion channel blocker, anthracene-9-carboxylic acid (A9C), indicative of the ascorbate release via anion channels. EPR spectroscopy measurements demonstrates that salinity (NaCl) triggers the accumulation of root apoplastic ascorbyl radicals in A9C-dependent manner, confirming that L-ascorbate leaks through anion channels under depolarisation. This mechanism may underlie ascorbate release, signalling phenomena, apoplastic redox reactions, iron acquisition and control the ionic and electrical equilibrium (together K+ efflux via GORK channels).

Volume-scalable high-brightness three-dimensional visible light source

DOEpatents

Subramania, Ganapathi; Fischer, Arthur J; Wang, George T; Li, Qiming

2014-02-18

A volume-scalable, high-brightness, electrically driven visible light source comprises a three-dimensional photonic crystal (3DPC) comprising one or more direct bandgap semiconductors. The improved light emission performance of the invention is achieved based on the enhancement of radiative emission of light emitters placed inside a 3DPC due to the strong modification of the photonic density-of-states engendered by the 3DPC.

Single-shot quantitative phase microscopy with color-multiplexed differential phase contrast (cDPC)

PubMed Central

2017-01-01

We present a new technique for quantitative phase and amplitude microscopy from a single color image with coded illumination. Our system consists of a commercial brightfield microscope with one hardware modification—an inexpensive 3D printed condenser insert. The method, color-multiplexed Differential Phase Contrast (cDPC), is a single-shot variant of Differential Phase Contrast (DPC), which recovers the phase of a sample from images with asymmetric illumination. We employ partially coherent illumination to achieve resolution corresponding to 2× the objective NA. Quantitative phase can then be used to synthesize DIC and phase contrast images or extract shape and density. We demonstrate amplitude and phase recovery at camera-limited frame rates (50 fps) for various in vitro cell samples and c. elegans in a micro-fluidic channel. PMID:28152023

Dynamic alteration of regional cerebral blood flow during carotid compression and proof of reversibility.

PubMed

Asahi, Kouichi; Hori, M; Hamasaki, N; Sato, S; Nakanishi, H; Kuwatsuru, R; Sasai, K; Aoki, S

2012-01-01

It is difficult to non-invasively visualize changes in regional cerebral blood flow caused by manual compression of the carotid artery. To visualize dynamic changes in regional cerebral blood flow during and after manual compression of the carotid artery. Two healthy volunteers were recruited. Anatomic features and flow directions in the circle of Willis were evaluated with time-of-flight magnetic resonance angiography (MRA) and two-dimensional phase-contrast (2DPC) MRA, respectively. Regional cerebral blood flow was visualized with territorial arterial spin-labeling magnetic resonance imaging (TASL-MRI). TASL-MRI and 2DPC-MRA were performed in three states: at rest, during manual compression of the right carotid artery, and after decompression. In one volunteer, time-space labeling inversion pulse (Time-SLIP) MRA was performed to confirm collateral flow. During manual carotid compression, in one volunteer, the right thalamus changed to be fed only by the vertebrobasilar system, and the right basal ganglia changed to be fed by the left internal carotid artery. In the other volunteer, the right basal ganglia changed to be fed by the vertebrobasilar system. 2DPC-MRA showed that the flow direction changed in the right A1 segment of the anterior cerebral artery and the right posterior communicating artery. Perfusion patterns and flow directions recovered after decompression. Time-SLIP MRA showed pial vessels and dural collateral circulation when the right carotid artery was manually compressed. Use of TASL-MRI and 2DPC-MRA was successful for non-invasive visualization of the dynamic changes in regional cerebral blood flow during and after manual carotid compression.

Isotropic differential phase contrast microscopy for quantitative phase bio-imaging.

PubMed

Chen, Hsi-Hsun; Lin, Yu-Zi; Luo, Yuan

2018-05-16

Quantitative phase imaging (QPI) has been investigated to retrieve optical phase information of an object and applied to biological microscopy and related medical studies. In recent examples, differential phase contrast (DPC) microscopy can recover phase image of thin sample under multi-axis intensity measurements in wide-field scheme. Unlike conventional DPC, based on theoretical approach under partially coherent condition, we propose a new method to achieve isotropic differential phase contrast (iDPC) with high accuracy and stability for phase recovery in simple and high-speed fashion. The iDPC is simply implemented with a partially coherent microscopy and a programmable thin-film transistor (TFT) shield to digitally modulate structured illumination patterns for QPI. In this article, simulation results show consistency of our theoretical approach for iDPC under partial coherence. In addition, we further demonstrate experiments of quantitative phase images of a standard micro-lens array, as well as label-free live human cell samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative differential phase contrast imaging at high resolution with radially asymmetric illumination.

PubMed

Lin, Yu-Zi; Huang, Kuang-Yuh; Luo, Yuan

2018-06-15

Half-circle illumination-based differential phase contrast (DPC) microscopy has been utilized to recover phase images through a pair of images along multiple axes. Recently, the half-circle based DPC using 12-axis measurements significantly provides a circularly symmetric phase transfer function to improve accuracy for more stable phase recovery. Instead of using half-circle-based DPC, we propose a new scheme of DPC under radially asymmetric illumination to achieve circularly symmetric phase transfer function and enhance the accuracy of phase recovery in a more stable and efficient fashion. We present the design, implementation, and experimental image data demonstrating the ability of our method to obtain quantitative phase images of microspheres, as well as live fibroblast cell samples.

Open circuit potential monitored digital photocorrosion of GaAs/AlGaAs quantum well microstructures

NASA Astrophysics Data System (ADS)

Aithal, Srivatsa; Dubowski, Jan J.

2018-04-01

Nanostructuring of semiconductor wafers with an atomic level depth resolution is a challenging task, primarily due to the limited availability of instruments for in situ monitoring of such processes. Conventional digital etching relies on calibration procedures and cumbersome diagnostics applied between or at the end of etching cycles. We have developed a photoluminescence (PL) based process for monitoring in situ digital photocorrosion (DPC) of GaAs/AlGaAs microstructures at rates below 0.2 nm per cycle. In this communication, we demonstrate that DPC of GaAs/AlGaAs microstructures could be monitored with open circuit potential (OCP) measured between the photocorroding surface of a microstructure and an Ag/AgCl reference electrode installed in the sample chamber. The excellent correlation between the position of both PL and OCP maxima indicates that the DPC process could be monitored in situ for materials that do not necessarily exhibit measurable PL emission.

MK-801, but not drugs acting at strychnine-insensitive glycine receptors, attenuate methamphetamine nigrostriatal toxicity.

PubMed

Layer, R T; Bland, L R; Skolnick, P

1993-10-15

Repeated administration of methamphetamine (METH) results in damage to nigrostriatal dopaminergic neurons. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists and use-dependent cation channel blockers attenuate METH-induced damage. The objectives of the present study were to examine whether comparable reductions in METH-induced damage could be obtained by compounds acting at strychnine-insensitive glycine receptors on the NMDA receptor complex. Four injections of METH (5 mg/kg i.p.) resulted in a approximately 70.9% depletion of striatal dopamine (DA) and approximately 62.7% depletion of dihydroxyphenylacetic acid (DOPAC) content, respectively. A significant protection against METH-induced DA and DOPAC depletion was afforded by the use-dependent channel blocker, MK-801. The competitive glycine antagonist 7-chlorokynurenic acid (7-Cl-KA), the low efficacy glycine partial agonist (+)-3-amino-1-hydroxy-2-pyrrolidone ((+)-HA-966), and the high efficacy partial glycine agonist 1-aminocyclopropane-carboxylic acid (ACPC) were ineffective against METH-induced toxicity despite their abilities to attenuate glutamate-induced neurotoxicity under both in vivo and in vitro conditions. These results indicate that glycinergic ligands do not possess the same broad neuroprotective spectrum as other classes of NMDA antagonists.

Direct pulp capping of permanent teeth in New Zealand general dental practice--a practice based research study.

PubMed

Friedlander, L; McElroy, K; Daniel, B; Cullinan, M; Hanlin, S

2015-06-01

This study aimed to investigate treatment protocols and opinions towards direct pulp capping (DPC) amongst New Zealand (NZ) general dental practitioners (GDP) through a Practice Based Research Network (PBRN) study. Mixed-methods approach using qualitative thematic and quantitative analysis. An on-line survey containing Likert scale items and open-ended questions was distributed to GDPs on the Dental Council of New Zealand (DCNZ) register (2012) to collect information on practitioner demographics, treatment protocols, continuing professional development (CPD) and philosophies towards DPC. RESULTs: Two hundred and ten GDPs from North and South Islands providing care in main centres and rural areas engaged with the PBRN and participated in the study. Almost all performed DPC treatment although it was not a common procedure. DPC was perceived as 'successful' or 'very successful' by 95% of respondents, mostly for cases of reversible pulpitis. Most provided DPC for patients of all ages but younger patients were perceived to have the best clinical outcomes. Calcium hydroxide and MTA were the most commonly used materials for DPC. MTA was believed to have the best outcome but cost and handling properties were barriers to its use. The majority of respondents had participated in CPD related to vital pulp therapy and regarded this treatment as conservative and providing time and financial benefits compared with more invasive treatment. Clinicians' timeframes for assessing healing were variable, and combined clinical and radiographic findings were considered most useful. New Zealand dentists perceive DPC as a successful and conservative treatment in selected cases. The findings have provided insights into engagement of NZ dentists in using research to inform everyday clinical practice through a PBRN study.

Impact of the Japanese Diagnosis Procedure Combination-based Payment System on cardiovascular medicine-related costs.

PubMed

Yasunaga, Hideo; Ide, Hiroo; Imamura, Tomoaki; Ohe, Kazuhiko

2005-09-01

In 2003, a lump-sum payment system based on Diagnosis Procedure Combinations (DPC) was introduced to 82 specific function hospitals in Japan. While the US DRG/PPS system is a "per case payment" system, the DPC based payment system adopts a "per day payment." It is generally believed that the Japanese system provides as much of an incentive as the DRG/PPS system to shorten the average length of stay (LOS). We performed an empirical analysis of the effect of LOS shortening on hospital revenue and expenditure under the DPC-based payment system, particularly in cardiovascular diseases. We also point out fundamentally controversial aspects of the current system. A total 109 cases were selected from patients hospitalized at the University of Tokyo Hospital from May to July, 2003 and classified into one of three categories: (1) cardiac catheter interventions, (2) cardiac catheter examinations, and (3) other conservative treatments. We analyzed the changes in profit per day in cases of a reduction in average LOS and an increase in the number of cases. In category (1) profit increased significantly in conjunction with reduced LOS. In category (2) profit increased only minimally. In category (3), profit increased rarely and sometimes decreased. In cases of conservative treatment, profits sometimes decreased because an increase in material costs exceeded the increase in revenue. It therefore became clear that the DPC-based payment system does not decisively provide an economic incentive to reduce LOS in cardiovascular medicine.

Direct peroral cholangioscopy using an ultrathin endoscope: making technique easier.

PubMed

Sola-Vera, Javier; Uceda, Francisco; Cuesta, Rubén; Vázquez, Narcís

2014-01-01

Cholangioscopy is a useful tool for the study and treatment of biliary pathology. Ultrathin upper endoscopes allow direct peroral cholangioscopy (DPC) but have some drawbacks. The aim of the study was to evaluate the success rate of DPC with an ultrathin endoscope using a balloon catheter to reach the biliary confluence. Prospective observational study. An ultrathin endoscope (Olympus XP180N, outer diameter 5.5 mm, working channel 2 mm) was used. To access the biliary tree, free-hand technique was used. To reach the biliary confluence an intraductal balloon catheter (Olympus B5-2Q diameter 1.9 mm) and a 0.025 inch guide wire was used. In all cases sphincterotomy and/or sphincteroplasty was performed. The success rate was defined as the percentage of cases in which the biliary confluence could be reached with the ultrathin endoscope. Fifteen patients (8 men/7 women) were included. Mean age was 77.7 + or - 10.8 years (range 45-91). The indications for cholangioscopy were suspected bile duct stones (n = 9), electrohydraulic lithotripsy for the treatment of difficult choledocholithiasis (n = 5) and evaluation of biliary stricture (n = 1). Access to the bile duct was achieved in 14/15 cases (93.3%). Biliary confluence was reached in 13/15 cases (86.7%). One complication was observed in one patient (oxigen desaturation). DPC with an ultrathin endoscope can be done with the free-hand technique. Intraductal balloon-guided DPC allows full examination of the common bile duct in most cases.

Structure reactivity and thermodynamic analysis on the oxidation of ampicillin drug by copper(III) complex in aqueous alkaline medium (stopped-flow technique)

NASA Astrophysics Data System (ADS)

Shetti, Nagaraj P.; Hegde, Rajesh N.; Nandibewoor, Sharanappa T.

2009-07-01

Oxidation of penicillin derivative, ampicillin (AMP) by diperiodatocuprate(III) (DPC) in alkaline medium at a constant ionic strength of 0.01-mol dm -3 was studied spectrophotometrically. The reaction between DPC and ampicillin in alkaline medium exhibits 1:4 stoichiometry (ampicillin:DPC). Intervention of free radicals was observed in the reaction. Based on the observed orders and experimental evidences, a mechanism involving the protonated form of DPC as the reactive oxidant species has been proposed. The oxidation reaction in alkaline medium has been shown to proceed via a DPC-AMP complex, which decomposes slowly in a rate determining step to yield phenyl glycine (PG) and free radical species of 6-aminopenicillanic acid (6-APA), followed by other fast steps to give the products. The two major products were characterized by IR, NMR, LC-MS and Spot test. The reaction constants involved in the different steps of the mechanism were calculated. The activation parameters with respect to slow step of the mechanism were computed and discussed and thermodynamic quantities were also determined.

Data Processing for a High Resolution Preclinical PET Detector Based on Philips DPC Digital SiPMs

NASA Astrophysics Data System (ADS)

Schug, David; Wehner, Jakob; Goldschmidt, Benjamin; Lerche, Christoph; Dueppenbecker, Peter Michael; Hallen, Patrick; Weissler, Bjoern; Gebhardt, Pierre; Kiessling, Fabian; Schulz, Volkmar

2015-06-01

In positron emission tomography (PET) systems, light sharing techniques are commonly used to readout scintillator arrays consisting of scintillation elements, which are smaller than the optical sensors. The scintillating element is then identified evaluating the signal heights in the readout channels using statistical algorithms, the center of gravity (COG) algorithm being the simplest and mostly used one. We propose a COG algorithm with a fixed number of input channels in order to guarantee a stable calculation of the position. The algorithm is implemented and tested with the raw detector data obtained with the Hyperion-II D preclinical PET insert which uses Philips Digital Photon Counting's (PDPC) digitial SiPMs. The gamma detectors use LYSO scintillator arrays with 30 ×30 crystals of 1 ×1 ×12 mm3 in size coupled to 4 ×4 PDPC DPC 3200-22 sensors (DPC) via a 2-mm-thick light guide. These self-triggering sensors are made up of 2 ×2 pixels resulting in a total of 64 readout channels. We restrict the COG calculation to a main pixel, which captures most of the scintillation light from a crystal, and its (direct and diagonal) neighboring pixels and reject single events in which this data is not fully available. This results in stable COG positions for a crystal element and enables high spatial image resolution. Due to the sensor layout, for some crystals it is very likely that a single diagonal neighbor pixel is missing as a result of the low light level on the corresponding DPC. This leads to a loss of sensitivity, if these events are rejected. An enhancement of the COG algorithm is proposed which handles the potentially missing pixel separately both for the crystal identification and the energy calculation. Using this advancement, we show that the sensitivity of the Hyperion-II D insert using the described scintillator configuration can be improved by 20-100% for practical useful readout thresholds of a single DPC pixel ranging from 17-52 photons. Furthermore, we show that the energy resolution of the scanner is superior for all readout thresholds if singles with a single missing pixel are accepted and correctly handled compared to the COG method only accepting singles with all neighbors present by 0-1.6% (relative difference). The presented methods can not only be applied to gamma detectors employing DPC sensors, but can be generalized to other similarly structured and self-triggering detectors, using light sharing techniques, as well.

Occurrence and fate of the angiotensin II receptor antagonist transformation product valsartan acid in the water cycle--a comparative study with selected β-blockers and the persistent anthropogenic wastewater indicators carbamazepine and acesulfame.

PubMed

Nödler, Karsten; Hillebrand, Olav; Idzik, Krzysztof; Strathmann, Martin; Schiperski, Ferry; Zirlewagen, Johannes; Licha, Tobias

2013-11-01

The substantial transformation of the angiotensin II receptor antagonist valsartan to the transformation product 2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-carboxylic acid (referred to as valsartan acid) during the activated sludge process was demonstrated in the literature and confirmed in the here presented study. However, there was a severe lack of knowledge regarding the occurrence and fate of this compound in surface water and its behavior during drinking water treatment. In this work a comparative study on the occurrence and persistency of valsartan acid, three frequently used β-blockers (metoprolol, atenolol, and sotalol), atenolol acid (one significant transformation product of atenolol and metoprolol), and the two widely distributed persistent anthropogenic wastewater indicators carbamazepine and acesulfame in raw sewage, treated wastewater, surface water, groundwater, and tap water is presented. Median concentrations of valsartan acid in the analyzed matrices were 101, 1,310, 69, <1.0, and 65 ng L(-1), respectively. Treated effluents from wastewater treatment plants were confirmed as significant source. Regarding concentration levels of pharmaceutical residues in surface waters valsartan acid was found just as relevant as the analyzed β-blockers and the anticonvulsant carbamazepine. Regarding its persistency in surface waters it was comparable to carbamazepine and acesulfame. Furthermore, removal of valsartan acid during bank filtration was poor, which demonstrated the relevance of this compound for drinking water suppliers. Regarding drinking water treatment (Muelheim Process) the compound was resistant to ozonation but effectively eliminated (≥90%) by subsequent activated carbon filtration. However, without applying activated carbon filtration the compound may enter the drinking water distribution system as it was demonstrated for Berlin tap water. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Use of Dodecylphosphocholine Micelles in Solution NMR

NASA Astrophysics Data System (ADS)

Kallick, D. A.; Tessmer, M. R.; Watts, C. R.; Li, C. Y.

Dodecylphosphocholine (DPC) micelles are useful as a model membrane system for solution NMR. Several new observations on dodecylphosphocholine micelles and their interactions with opioid peptides are described. The optimal lipid concentration has been investigated for small peptide NMR studies in DPC micelles for two opioid peptides, a 5-mer and a 17-mer. In contrast to reports in the literature, identical 2D spectra have been observed at low and high lipid concentrations. The chemical shift of resolved peptide proton resonances has been followed as a function of added lipid and indicates that there are changes in the chemical shifts above the critical micelle concentration and up to a ratio of 7:1 (lipid:peptide) for the 17-mer, and 9.6:1 for the 5-mer. These results suggest that conformational changes occur in the peptide significantly above the critical micelle concentration, up to a lipid:peptide ratio which is dependent upon the peptide, here ranging from 7:1 to 9.6:1. To address the stoichiometry more directly, the diffusion coefficients of the lipid alone and the lipid with peptide have been measured using pulsed-field gradient spin-echo NMR experiments. These data have been used to calculate the hydrodynamic radius and the aggregation number of the micelle with and without peptide and show that the aggregation number of the peptide-lipid complex increases at high lipid concentrations without a concomitant change in the peptide conformation. Last, several protonated impurities have been observed in the commercial preparation of DPC which resonate in the amide proton region of the NMR spectrum. These results are significant for researchers using DPC micelles and illustrate that both care in sample preparation and the stoichiometry are important issues with the use of DPC as a model membrane.

Chloride channel function is linked to epithelium-dependent airway relaxation.

PubMed

Fortner, C N; Lorenz, J N; Paul, R J

2001-02-01

We previously reported that substance P (SP) and ATP evoke transient, epithelium-dependent relaxation of mouse tracheal smooth muscle. Since both SP and ATP are known to evoke transepithelial Cl- secretion across epithelial monolayers, we tested the hypothesis that epithelium-dependent relaxation of mouse trachea depends on Cl- channel function. In perfused mouse tracheas, the responses to SP and ATP were both inhibited by the Cl- channel inhibitors diphenylamine-2-carboxylate and 5-nitro-2-(3-phenylpropylamino)benzoate. Relaxation to ATP or SP was unaffected by 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), and relaxation to SP was unaffected by either DIDS or DNDS. Replacing Cl- in the buffer solutions with the impermeable anion gluconate on both sides of the trachea inhibited relaxation to SP or ATP. In contrast, increasing the gradient for Cl- secretion using Cl- free medium only in the tracheal lumen enhanced the relaxation to SP or ATP. We conclude that Cl- channel function is linked to receptor-mediated, epithelium-dependent relaxation. The finding that relaxation to SP was not blocked by DIDS suggested the involvement of a DIDS-insensitive Cl- channel, potentially the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. To test this hypothesis, we evaluated tracheas from CFTR-deficient mice and found that the peak relaxation to SP or ATP was not significantly different from those responses in wild-type littermates. This suggests that a DIDS-insensitive Cl- channel other than CFTR is active in the SP response. This work introduces a possible role for Cl- pathways in the modulation of airway smooth muscle function and may have implications for fundamental studies of airway function as well as therapeutic approaches to pulmonary disease.

TU-CD-207-12: Impact of Anatomical Noise On Detection Performance of Microcalcifications in Multi-Contrast Breast Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garrett, J; Ge, Y; Li, K

2015-06-15

Purpose: The anatomical noise power spectra (NPS) for differential phase contrast (DPC) and dark field (DF) imaging have recently been characterized using a power-law model with two parameters, alpha and beta, an innovative extension to the methodology used in x-ray attenuation based breast imaging such as mammography, DBT, or cone-beam CT. Beta values of 3.6, 2.6, and 1.3 have been measured for absorption, DPC, and DF respectively for cadaver breasts imaged in the coronal plane; these dramatic differences should be reflected in their detection performance. The purpose of this study was to determine the impact of anatomical noise on breastmore » calcification detection and compare the detection performance of the three contrast mechanisms of a multi-contrast x-ray imaging system. Methods: In our studies, a calcification image object was segmented out of the multi-contrast images of a cadaver breast specimen. 50 measured total NPS were measured from breast cadavers directly. The ideal model observer detectability was calculated for a range of doses (5–100%) and a range of calcification sizes (diameter = 0.25–2.5 mm). Results: Overall we found the highest average detectability corresponded to DPC imaging (7.4 for 1 mm calc.), with DF the next highest (3.8 for 1 mm calc.), and absorption the lowest (3.2 for 1 mm calc.). However, absorption imaging also showed the slowest dependence on dose of the three modalities due to the significant anatomical noise. DPC showed a peak detectability for calcifications ∼1.25 mm in diameter, DF showed a peak for calcifications around 0.75 mm in diameter, and absorption imaging had no such peak in the range explored. Conclusion: Understanding imaging performance for DPC and DF is critical to transition these modalities to the clinic. The results presented here offer new insight into how these modalities complement absorption imaging to maximize the likelihood of detecting early breast cancers. J. Garrett, Y. Ge, K. Li: Nothing to disclose. G.-H. Chen: Research funded, GE Healthcare; Research funded, Siemens AX.« less

Critical currents of Nb sub 3 Sn wires for the US-DPC coil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takayasu, M.; Gung, C.Y.; Steeves, M.M.

1991-03-01

This paper evaluates the critical current of titanium-alloyed internal-tin, jelly-roll Nb{sub 3}Sn wire for use in the US-DPC coil. It was confirmed from 14 randomly-selected samples that the critical-current values were uniform and consistent: the non-copper critical-current density was approximately 700 A/mm{sup 2} at 10 T and 4.2 K in agreement with expectations. A 27-strand cable-in-conduit conductor (CICC) using the low-thermal-coefficient-of-expansion superalloy Incoloy 905 yielded a critical current 5--7% below the average value of the single-strand data.

Evidence for High Concentrations and Maternal Transfer of Substituted Diphenylamines in European Eels Analyzed by Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry and Gas Chromatography-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

PubMed

Sühring, Roxana; Ortiz, Xavier; Pena-Abaurrea, Miren; Jobst, Karl J; Freese, Marko; Pohlmann, Jan-Dag; Marohn, Lasse; Ebinghaus, Ralf; Backus, Sean; Hanel, Reinhold; Reiner, Eric J

2016-12-06

Chemical pollution is hypothesized to be one of the factors driving the strong decline of the critically endangered European eel population. Specifically, the impact of contaminants on the quality of spawning eels and subsequent embryo survival and development has been discussed as crucial investigation point. However, so far, only very limited information on potential negative effects of contaminants on the reproduction of eels is available. Through the combination of nontargeted ultrahigh-resolution mass spectrometry and multidimensional gas chromatography, combined with more-conventional targeted analytical approaches and multimedia mass-balance modeling, compounds of particular relevance, and their maternal transfer in artificially matured European eels from the German river Ems have been identified. Substituted diphenylamines were, unexpectedly, found to be the primary organic contaminants in the eel samples, with concentrations in the μg g -1 wet weight range. Furthermore, it could be shown that these contaminants, as well as polychlorinated biphenyls (PCBs), organochlorine pesticides, and polyaromatic hydrocarbons (PAHs), are not merely stored in lipid rich tissue of eels but maternally transferred into gonads and eggs. The results of this study provide unique information on both the fate and behavior of substituted diphenylamines in the environment as well as their relevance as contaminants in European eels.

Doctor-patient communication without family is most frequently practiced in patients with malignant tumors in home medical care settings.

PubMed

Kimura, Takuma; Imanaga, Teruhiko; Matsuzaki, Makoto

2014-01-01

Promotion of home medical care is absolutely necessary in Japan where is a rapidly aging society. In home medical care settings, triadic communications among the doctor, patient and the family are common. And "communications just between the doctor and the patient without the family" (doctor-patient communication without family, "DPC without family") is considered important for the patient to frankly communicate with the doctor without consideration for the family. However, the circumstances associated with DPC without family are unclear. Therefore, to identify the factors of the occurrence of DPC without family, we conducted a cross-sectional mail-in survey targeting 271 families of Japanese patients who had previously received home medical care. Among 227 respondents (83.8%), we eventually analyzed data from 143, excluding families of patients with severe hearing or cognitive impairment and severe verbal communication dysfunction. DPC without family occurred in 26.6% (n = 38) of the families analyzed. A multivariable logistic regression analysis was performed using a model including Primary disease, Daily activity, Duration of home medical care, Interval between doctor visits, Duration of doctor's stay, Existence of another room, and Spouse as primary caregiver. As a result, DPC without family was significantly associated with malignant tumor as primary disease (OR, 3.165; 95% CI, 1.180-8.486; P = 0.022). In conclusion, the visiting doctors should bear in mind that the background factor of the occurrence of DPC without family is patient's malignant tumors.

Overlapping parietal activity in memory and perception: evidence for the attention to memory model.

PubMed

Cabeza, Roberto; Mazuz, Yonatan S; Stokes, Jared; Kragel, James E; Woldorff, Marty G; Ciaramelli, Elisa; Olson, Ingrid R; Moscovitch, Morris

2011-11-01

The specific role of different parietal regions to episodic retrieval is a topic of intense debate. According to the Attention to Memory (AtoM) model, dorsal parietal cortex (DPC) mediates top-down attention processes guided by retrieval goals, whereas ventral parietal cortex (VPC) mediates bottom-up attention processes captured by the retrieval output or the retrieval cue. This model also hypothesizes that the attentional functions of DPC and VPC are similar for memory and perception. To investigate this last hypothesis, we scanned participants with event-related fMRI whereas they performed memory and perception tasks, each comprising an orienting phase (top-down attention) and a detection phase (bottom-up attention). The study yielded two main findings. First, consistent with the AtoM model, orienting-related activity for memory and perception overlapped in DPC, whereas detection-related activity for memory and perception overlapped in VPC. The DPC overlap was greater in the left intraparietal sulcus, and the VPC overlap in the left TPJ. Around overlapping areas, there were differences in the spatial distribution of memory and perception activations, which were consistent with trends reported in the literature. Second, both DPC and VPC showed stronger connectivity with medial-temporal lobe during the memory task and with visual cortex during the perception task. These findings suggest that, during memory tasks, some parietal regions mediate similar attentional control processes to those involved in perception tasks (orienting in DPC vs. detection in VPC), although on different types of information (mnemonic vs. sensory).

A PET detector prototype based on digital SiPMs and GAGG scintillators.

PubMed

Schneider, Florian R; Shimazoe, Kenji; Somlai-Schweiger, Ian; Ziegler, Sibylle I

2015-02-21

Silicon Photomultipliers (SiPM) are interesting light sensors for Positron Emission Tomography (PET). The detector signal of analog SiPMs is the total charge of all fired cells. Energy and time information have to be determined with dedicated readout electronics. Philips Digital Photon Counting has developed a SiPM with added electronics on cell level delivering a digital value of the time stamp and number of fired cells. These so called Digital Photon Counters (DPC) are fully digital devices. In this study, the feasibility of using DPCs in combination with LYSO (Lutetium Yttrium Oxyorthosilicate) and GAGG (Gadolinium Aluminum Gallium Garnet) scintillators for PET is tested. Each DPC module has 64 channels with 3.2 × 3.8775 mm(2), comprising 3200 cells each. GAGG is a recently developed scintillator (Zeff = 54, 6.63 g cm(-3), 520 nm peak emission, 46 000 photons MeV(-1), 88 ns (92%) and 230 ns (8%) decay times, non-hygroscopic, chemically and mechanically stable). Individual crystals of 2 × 2 × 6 mm(3) were coupled onto each DPC pixel. LYSO coupled to the DPC results in a coincidence time resolution (CTR) of 171 ps FWHM and an energy resolution of 12.6% FWHM at 511 keV. Using GAGG, coincidence timing is 310 ps FWHM and energy resolution is 8.5% FWHM. A PET detector prototype with 2 DPCs equipped with a GAGG array matching the pixel size (3.2 × 3.8775 × 8 mm(3)) was assembled. To emulate a ring of 10 modules, objects are rotated in the field of view. CTR of the PET is 619 ps and energy resolution is 9.2% FWHM. The iterative MLEM reconstruction is based on system matrices calculated with an analytical detector response function model. A phantom with rods of different diameters filled with (18)F was used for tomographic tests.

A PET detector prototype based on digital SiPMs and GAGG scintillators

NASA Astrophysics Data System (ADS)

Schneider, Florian R.; Shimazoe, Kenji; Somlai-Schweiger, Ian; Ziegler, Sibylle I.

2015-02-01

Silicon Photomultipliers (SiPM) are interesting light sensors for Positron Emission Tomography (PET). The detector signal of analog SiPMs is the total charge of all fired cells. Energy and time information have to be determined with dedicated readout electronics. Philips Digital Photon Counting has developed a SiPM with added electronics on cell level delivering a digital value of the time stamp and number of fired cells. These so called Digital Photon Counters (DPC) are fully digital devices. In this study, the feasibility of using DPCs in combination with LYSO (Lutetium Yttrium Oxyorthosilicate) and GAGG (Gadolinium Aluminum Gallium Garnet) scintillators for PET is tested. Each DPC module has 64 channels with 3.2 × 3.8775 mm2, comprising 3200 cells each. GAGG is a recently developed scintillator (Zeff = 54, 6.63 g cm-3, 520 nm peak emission, 46 000 photons MeV-1, 88 ns (92%) and 230 ns (8%) decay times, non-hygroscopic, chemically and mechanically stable). Individual crystals of 2 × 2 × 6 mm3 were coupled onto each DPC pixel. LYSO coupled to the DPC results in a coincidence time resolution (CTR) of 171 ps FWHM and an energy resolution of 12.6% FWHM at 511 keV. Using GAGG, coincidence timing is 310 ps FWHM and energy resolution is 8.5% FWHM. A PET detector prototype with 2 DPCs equipped with a GAGG array matching the pixel size (3.2 × 3.8775 × 8 mm3) was assembled. To emulate a ring of 10 modules, objects are rotated in the field of view. CTR of the PET is 619 ps and energy resolution is 9.2% FWHM. The iterative MLEM reconstruction is based on system matrices calculated with an analytical detector response function model. A phantom with rods of different diameters filled with 18F was used for tomographic tests.

One hospital, one appendectomy: The cost effectiveness of a standardized doctor's preference card.

PubMed

Skarda, David E; Rollins, Michael; Andrews, Seth; McFadden, Molly; Barnhart, Doug; Meyers, Rebecka; Scaife, Eric

2015-06-01

Appendicitis in children provides a unique opportunity to explore changes that reduce variation, reduce cost, and improve value. In this study we sought to evaluate the effectiveness of standardization of surgical technique and intraoperative disposable device utilization for laparoscopic appendectomy among all surgeons at a tertiary children's hospital. All 6 surgeons at our tertiary children's hospital agreed to standardize to a single technique of performing a laparoscopic appendectomy. We collected data on all pediatric patients who had a laparoscopic appendectomy following implementation of the uniform doctor's preference card (DPC) (March 1, 2013 to February 28, 2014) and compared them to a historical control group. Implementation of the uniform DPC decreased the device cost per appendectomy from $844.11 to $305.32. Operative times (skin incision to skin closure) were 34.8 minutes prior to the uniform DPC and 37.0 minutes using the uniform DPC. There were no significant differences in postappendectomy outcomes. We have demonstrated that implementation of a uniform DPC and technical standardization for laparoscopic appendectomy can significantly reduce cost. Furthermore, this can occur without dramatically increasing operative times, length of stay, or postoperative complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Nuclear proteome analysis of undifferentiated mouse embryonic stem and germ cells.

PubMed

Buhr, Nicolas; Carapito, Christine; Schaeffer, Christine; Kieffer, Emmanuelle; Van Dorsselaer, Alain; Viville, Stéphane

2008-06-01

Embryonic stem cells (ESCs) and embryonic germ cells (EGCs) provide exciting models for understanding the underlying mechanisms that make a cell pluripotent. Indeed, such understanding would enable dedifferentiation and reprogrammation of any cell type from a patient needing a cell therapy treatment. Proteome analysis has emerged as an important technology for deciphering these biological processes and thereby ESC and EGC proteomes are increasingly studied. Nevertheless, their nuclear proteomes have only been poorly investigated up to now. In order to investigate signaling pathways potentially involved in pluripotency, proteomic analyses have been performed on mouse ESC and EGC nuclear proteins. Nuclei from ESCs and EGCs at undifferentiated stage were purified by subcellular fractionation. After 2-D separation, a subtractive strategy (subtracting culture environment contaminating spots) was applied and a comparison of ESC, (8.5 day post coïtum (dpc))-EGC and (11.5 dpc)-EGC specific nuclear proteomes was performed. A total of 33 ESC, 53 (8.5 dpc)-EGC, and 36 (11.5 dpc)-EGC spots were identified by MALDI-TOF-MS and/or nano-LC-MS/MS. This approach led to the identification of two isoforms (with and without N-terminal acetylation) of a known pluripotency marker, namely developmental pluripotency associated 5 (DPPA5), which has never been identified before in 2-D gel-MS studies of ESCs and EGCs. Furthermore, we demonstrated the efficiency of our subtracting strategy, in association with a nuclear subfractionation by the identification of a new protein (protein arginine N-methyltransferase 7; PRMT7) behaving as proteins involved in pluripotency.

H2 blockers

MedlinePlus

Peptic ulcer disease - H2 blockers; PUD - H2 blockers; Gastroesophageal reflux - H2 blockers; GERD - H2 blockers ... provider about your symptoms. If you have a peptic ulcer, your provider may prescribe H2 blockers along with ...

Simple & Safe Genomic DNA Isolation.

ERIC Educational Resources Information Center

Moss, Robert; Solomon, Sondra

1991-01-01

A procedure for purifying DNA using either bacteria or rat liver is presented. Directions for doing a qualitative DNA assay using diphenylamine and a quantitative DNA assay using spectroscopy are included. (KR)

Diversion procto-colitis: response to treatment with short-chain fatty acids.

PubMed

Kiely, E M; Ajayi, N A; Wheeler, R A; Malone, M

2001-10-01

Diversion procto-colitis (DPC) results from a deficiency of luminal short-chain fatty acids (SCFAs). Endoscopic and histopathologic features of the disorder are almost universally present in defunctioned bowel, but symptomatic DPC is less common. Five children with symptomatic DPC underwent endoscopy and rectosigmoid biopsies. An endoscopic index (EI) was used to quantify disease severity. An SCFA mixture was administered into the defunctioned bowel. A good clinical response and improvement in the endoscopic index occurred in all children. Undiversion or rectal excision was carried out in 4 and was curative in each case. One child is awaiting a redo pull through. DPC should be considered in children with a defunctioned colon presenting with evidence of colitis. Histopathology provides supportive evidence and SCFAs may provide effective relief of symptoms. Stoma reversal or rectal excision is curative. Copyright 2001 by W.B. Saunders Company.

Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

NASA Astrophysics Data System (ADS)

Harasztosi, Csaba; Gummer, Anthony W.

2011-11-01

The voltage-dependent chloride-channel blocker anthracene-9-carboxylic acid (9AC) has been found to reduce the imaginary but not the real part of the mechanical impedance of the organ of Corti, suggesting that the effective stiffness of outer hair cells (OHCs) is reduced by 9AC. To examine whether 9AC interacts directly with the motor protein prestin to reduce the membrane component of the impedance, the patch-clamp technique in whole-cell configuration was used to measure the nonlinear capacitance (NLC) of isolated OHCs and, as control, prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9AC significantly reduced the NLC of both OHCs and HEK293 cells. Intracellular 9AC did not influence the blocking effect of the extracellular applied drug. These results suggest that 9AC interacts directly with prestin, reducing the effective stiffness of the motor, and that the interaction is extracellular.

21 CFR 177.1590 - Polyester elastomers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... dimethyl isophthalate—is made to react with alpha-hydroomega-hydroxypoly (oxytetramethylene) and/or 1,4... substances Limitations 4,4′ - Bis (alpha, alpha-dimethyl-benzyl) diphenylamine For use only as an antioxidant...

21 CFR 177.1590 - Polyester elastomers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... dimethyl isophthalate—is made to react with alpha-hydroomega-hydroxypoly (oxytetramethylene) and/or 1,4... substances Limitations 4,4′ - Bis (alpha, alpha-dimethyl-benzyl) diphenylamine For use only as an antioxidant...

Study of the in vitro metabolism of TJ0711 using ultra high performance liquid chromatography with quadrupole time-of-flight and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry.

PubMed

Hu, Lei; Lv, Zhenhua; Li, Gao; Xu, Xiaolong; Zhang, Chenghao; Cao, Peng; Huang, Jiangeng; Si, Luqin

2015-06-01

TJ0711 (1-[4-(2-methoxyethyl)phenoxy]-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol) is a novel β-adrenoreceptor blocker with vasodilating activity. The aim of this study was to investigate the in vitro metabolic properties of TJ0711 from both qualitative and quantitative aspects using mouse, rat, dog, and human liver microsomes as well as rat hepatocytes. Two modern liquid chromatography with tandem mass spectrometry systems, ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry, were utilized for the analysis. To better characterize the metabolic pathways of TJ0711, two major metabolites were incubated under the same conditions as that for TJ0711. TJ0711 was extensively metabolized in vitro, and a total of 34 metabolites, including 19 phase I and 15 phase II metabolites, were identified. Similar metabolite profiles were observed among species, and demethylation, hydroxylation, carboxylic acid formation, and glucuronidation were proposed as the major metabolic routes. Significant interspecies differences were observed in the metabolic stability studies of TJ0711. Furthermore, gender differences were significant in mice, rats, and dogs, but were negligible in humans. The valuable information provided in this work will be useful in planning and interpreting further pharmacokinetic, in vivo metabolism and toxicological studies of this novel β-blocker. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phase contrast STEM for thin samples: Integrated differential phase contrast.

PubMed

Lazić, Ivan; Bosch, Eric G T; Lazar, Sorin

2016-01-01

It has been known since the 1970s that the movement of the center of mass (COM) of a convergent beam electron diffraction (CBED) pattern is linearly related to the (projected) electrical field in the sample. We re-derive a contrast transfer function (CTF) for a scanning transmission electron microscopy (STEM) imaging technique based on this movement from the point of view of image formation and continue by performing a two-dimensional integration on the two images based on the two components of the COM movement. The resulting integrated COM (iCOM) STEM technique yields a scalar image that is linear in the phase shift caused by the sample and therefore also in the local (projected) electrostatic potential field of a thin sample. We confirm that the differential phase contrast (DPC) STEM technique using a segmented detector with 4 quadrants (4Q) yields a good approximation for the COM movement. Performing a two-dimensional integration, just as for the COM, we obtain an integrated DPC (iDPC) image which is approximately linear in the phase of the sample. Beside deriving the CTFs of iCOM and iDPC, we clearly point out the objects of the two corresponding imaging techniques, and highlight the differences to objects corresponding to COM-, DPC-, and (HA) ADF-STEM. The theory is validated with simulations and we present first experimental results of the iDPC-STEM technique showing its capability for imaging both light and heavy elements with atomic resolution and a good signal to noise ratio (SNR). Copyright © 2015 Elsevier B.V. All rights reserved.

Embryonic lethality in mice lacking mismatch-specific thymine DNA glycosylase is partially prevented by DOPS, a precursor of noradrenaline.

PubMed

Saito, Yusuke; Ono, Tetsuya; Takeda, Naoki; Nohmi, Takehiko; Seki, Masayuki; Enomoto, Takemi; Noda, Tetsuo; Uehara, Yoshihiko

2012-01-01

Thymine DNA glycosylase (TDG) is involved in the repair of G:T and G:U mismatches caused by hydrolytic deamination of 5-methylcytosine and cytosine, respectively. Recent studies have shown that TDG not only has G-T/U glycosylase activities but also acts in the maintaining proper epigenetic status. In order to investigate the function of TDG in vivo, mice lacking Tdg, Tdg (-/-), were generated. Tdg mutant mice died in utero by 11.5 days post coitum (dpc), although there were no significant differences in the spontaneous mutant frequencies between wild type and Tdg (-/-) embryos. On the other hand, the levels of noradrenaline in 10.5 dpc whole embryos, which is necessary for normal embryogenesis, were dramatically reduced in Tdg (-/-) embryos. Consequently, we tested the effect of D, L-threo-3, 4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline, on the survival of the Tdg (-/-) embryos. DOPS was given to pregnant Tdg (+/-) mice from 6.5 dpc through drinking water. Most of the Tdg (-/-) embryos were alive at 11.5 dpc, and they were partially rescued up to 14.5 dpc by the administration of DOPS. In contrast, the administration of L-3, 4-dihydroxyphenylalanine (L-DOPA) had marginal effects on Tdg (-/-) embryonic lethality. No embryo was alive without DOPS beyond 11.5 dpc, suggesting that the lethality in (-/-) embryos is partially due to the reduction of noradrenaline. These results suggest that embryonic lethality in Tdg (-/-) embryos is due, in part, to the reduction of noradrenaline levels.

Synthesis, structural characterization and density functional studies of ethyl 4-(biphenyl-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate A non-merohedral twinned structure

NASA Astrophysics Data System (ADS)

Yıdırım, Sema Öztürk; Büyükmumcu, Zeki; Butcher, Ray J.; Çetin, Gökalp; Şimşek, Rahime; Şafak, Cihat

2018-07-01

1,4-Dihydropyridine (1,4-DHP) derivatives have the reducing effect of extracellular Ca2+ ions influx on the L-type calcium channel. Because of this effect many 1,4-DHP derivatives are potent calcium channel blockers and antihypertensive agents. The biphenyl group is present in the structures of the most biologically active compounds and thus is an important group. By introducing this moiety into the structure of various compounds, active compounds are obtained. Thus, pharmacologically active structures can be condensed with the biphenyl structure to achieve novel biologically active compounds or compounds with increased activity. In this study, to achieve an active calcium channel blocker compound, the biphenyl group was introduced into the 1,4-DHP structure. The structure of the compound is proved by IR, 1H NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic activity assays have continued and positive results have been obtained. The phenyl rings [C16-C21 and C22-C27] make dihedral angles of 84.4 (1) and 87.5 (1)°, respectively, with the 1,4-dihydropyridine ring [N1/C1/C4-C9]. In the crystal, adjacent molecules are linked by Nsbnd H … O and Csbnd H … O hydrogen bonds into chains parallel to [010].

Small Arms Powder Manufacture in Germany

DTIC Science & Technology

1945-10-16

used were as follows: A. Nit ro--cellulose. B. Diphenylamine. C. Alcohol and Ether. D. Graphite. "E. Camphor . F. Contralite. G. Pottasium Sulfate. -3...about the other raw materials used. Graphite, camphor and centralite were added as.coat.ing materials. The potassium sulfate served as a flash...warm for 2 (two) hours. Centralit I is used on all powders, sometimes in conjunction with Diamylphthalate (Amylol) or camphor . The amount of

Exopolysaccharide-producing probiotic Lactobacilli reduce serum cholesterol and modify enteric microbiota in ApoE-deficient mice.

PubMed

London, Lis E E; Kumar, Arun H S; Wall, Rebecca; Casey, Pat G; O'Sullivan, Orla; Shanahan, Fergus; Hill, Colin; Cotter, Paul D; Fitzgerald, Gerald F; Ross, R Paul; Caplice, Noel M; Stanton, Catherine

2014-12-01

Probiotic bacteria have been associated with a reduction in cardiovascular disease risk, a leading cause of death and disability. The aim of this study was to assess the impact of dietary administration of exopolysaccharide-producing probiotic Lactobacillus cultures on lipid metabolism and gut microbiota in apolipoprotein E (apoE)-deficient mice. First, we examined lipid metabolism in response to dietary supplementation with recombinant β-glucan-producing Lactobacillus paracasei National Food Biotechnology Centre (NFBC) 338 expressing the glycosyltransferase (Gtf) gene from Pediococcus parvulus 2.6 (GTF), and naturally exopolysaccharide-producing Lactobacillus mucosae Dairy Product Culture Collection (DPC) 6426 (DPC 6426) compared with the non-β-glucan-producing isogenic control strain Lactobacillus paracasei NFBC 338 (PNZ) and placebo (15% wt:vol trehalose). Second, we examined the effects on the gut microbiota of dietary administration of DPC 6426 compared with placebo. Probiotic Lactobacillus strains at 1 × 10(9) colony-forming units/d per animal were administered to apoE(-/-) mice fed a high-fat (60% fat)/high-cholesterol (2% wt:wt) diet for 12 wk. At the end of the study, aortic plaque development and serum, liver, and fecal variables involved in lipid metabolism were analyzed, and culture-independent microbial analyses of cecal content were performed. Total cholesterol was reduced in serum (P < 0.001; ∼33-50%) and liver (P < 0.05; ∼30%) and serum triglyceride concentrations were reduced (P < 0.05; ∼15-25%) in mice supplemented with GTF or DPC 6426 compared with the PNZ or placebo group, respectively. In addition, dietary intervention with GTF led to increased amounts of fecal cholesterol excretion (P < 0.05) compared with all other groups. Compositional sequencing of the gut microbiota revealed a greater prevalence of Porphyromonadaceae (P = 0.001) and Prevotellaceae (P = 0.001) in the DPC 6426 group and lower proportions of Clostridiaceae (P < 0.05), Peptococcaceae (P < 0.001), and Staphylococcaceae (P < 0.01) compared with the placebo group. Ingestion of exopolysaccharide-producing lactobacilli resulted in seemingly favorable improvements in lipid metabolism, which were associated with changes in the gut microbiota of mice. © 2014 American Society for Nutrition.

Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out.

PubMed

Miura, Shin-ichiro; Matsuo, Yoshino; Nakayama, Asuka; Tomita, Sayo; Suematsu, Yasunori; Saku, Keijiro

2014-03-01

The recently approved angiotensin II (Ang II) type 1 (AT1) receptor blocker (ARB) azilsartan strongly reduces blood pressure (BP) in patients with hypertension. We previously reported that azilsartan showed unique binding behavior to the AT1 receptor because of its 5-oxo-1,2,4-oxadiazole moiety. However, the ability of azilsartan to block Ang II-dependent AT1 receptor activation is not yet clear. Azilsartan and a derivative of azilsartan (azilsartan-7H) that lacks a carboxyl group at the benzimidazole ring were used. Ang II-induced inositol phosphate (IP) production and extracellular signal-regulated kinase (ERK) activation were analyzed in a cell-based wash-out assay. Azilsartan, but not azilsartan-7H, completely blocked Ang II-induced IP production and ERK activation. Our previous report demonstrated that azilsartan mainly interacts with Tyr(113), Lys(199), and Gln(257) in the AT1 receptor. The interactions between azilsartan and Tyr(113) and Gln(257), but not Lys(199), were critical for blocking Ang II-induced IP production and ERK activation after wash-out. Although our findings regarding the molecule-specific effects of azilsartan are based on basic research, they may lead to an exciting insight into the mechanism of azilsartan.

A new method for fusion, denoising and enhancement of x-ray images retrieved from Talbot-Lau grating interferometry.

PubMed

Scholkmann, Felix; Revol, Vincent; Kaufmann, Rolf; Baronowski, Heidrun; Kottler, Christian

2014-03-21

This paper introduces a new image denoising, fusion and enhancement framework for combining and optimal visualization of x-ray attenuation contrast (AC), differential phase contrast (DPC) and dark-field contrast (DFC) images retrieved from x-ray Talbot-Lau grating interferometry. The new image fusion framework comprises three steps: (i) denoising each input image (AC, DPC and DFC) through adaptive Wiener filtering, (ii) performing a two-step image fusion process based on the shift-invariant wavelet transform, i.e. first fusing the AC with the DPC image and then fusing the resulting image with the DFC image, and finally (iii) enhancing the fused image to obtain a final image using adaptive histogram equalization, adaptive sharpening and contrast optimization. Application examples are presented for two biological objects (a human tooth and a cherry) and the proposed method is compared to two recently published AC/DPC/DFC image processing techniques. In conclusion, the new framework for the processing of AC, DPC and DFC allows the most relevant features of all three images to be combined in one image while reducing the noise and enhancing adaptively the relevant image features. The newly developed framework may be used in technical and medical applications.

An application in cheddar cheese manufacture for a strain of Lactococcus lactis producing a novel broad-spectrum bacteriocin, lacticin 3147.

PubMed Central

Ryan, M P; Rea, M C; Hill, C; Ross, R P

1996-01-01

Lactococcus lactis DPC3147, a strain isolated from an Irish kefir grain, produces a bacteriocin with a broad spectrum of inhibition. The bacteriocin produced is heat stable, particularly at a low pH, and inhibits nisin-producing (Nip+) lactococci. On the basis of the observation that the nisin structural gene (nisA) does not hybridize to DPC3147 genomic DNA, the bacteriocin produced was considered novel and designated lacticin 3147. The genetic determinants which encode lacticin 3147 are contained on a 63-kb plasmid, which was conjugally mobilized to a commercial cheese starter, L. lactis subsp. cremoris DPC4268. The resultant transconjugant, DPC4275, both produces and is immune to lacticin 3147. The ability of lacticin 3147-producing lactococci to perform as cheddar cheese starters was subsequently investigated in cheesemaking trials. Bacteriocin-producing starters (which included the transconjugant strain DPC4275) produced acid at rates similar to those of commercial strains. The level of lacticin 3147 produced in cheese remained constant over 6 months of ripening and correlated with a significant reduction in the levels of nonstarter lactic acid bacteria. Such results suggest that these starters provide a means of controlling developing microflora in ripened fermented products. PMID:8593062

Open abdominal management after damage-control laparotomy for trauma: a prospective observational American Association for the Surgery of Trauma multicenter study.

PubMed

Dubose, Joseph J; Scalea, Thomas M; Holcomb, John B; Shrestha, Binod; Okoye, Obi; Inaba, Kenji; Bee, Tiffany K; Fabian, Timothy C; Whelan, James; Ivatury, Rao R

2013-01-01

We conducted a prospective observational multi-institutional study to examine the natural history of the open abdomen (OA) after trauma and identify risk factors for failure to achieve definitive primary fascial closure (DPC) after OA use in trauma. Adults requiring OA for trauma were enrolled during a 2-year period. Demographics, presentation, and management variables were used to compare primary fascial closure and non-primary fascial closure patients, with logistic regression used to identify independent risk factors for failure to achieve primary fascial closure. A total of 572 patients from 14 American College of Surgeons-verified Level I trauma centers were enrolled. The majority were male (79%), mean (SD) age 39 (17) years. Injury Severity Score (ISS) was 15 or greater in 85% of patients and 84% had an abdominal Abbreviated Injury Scale (AIS) score of 3 or greater. Overall mortality was 23%. Initial primary fascial closure with unaltered native fascia was achieved in 379 patients (66%). Patients surviving at least 48 hours were grouped into those achieving DPC and those who did not achieve DPC after OA use. After logistic regression, independent risk factors for failure to achieve DPC included the number of reexplorations required (adjusted odds ratio [AOR], 1.3; 95% confidence interval (CI), 1.2-1.6; p < 0.001) the development of intra-abdominal abscess/sepsis (AOR, 2.4; 95% CI, 1.2-4.8; p = 0.011) bloodstream infection (AOR, 2.6; 95% CI, 1.2-5.7; p = 0.017), acute renal failure (AOR, 2.3; 95% CI, 1.2-5.7; p = 0.007), enteric fistula (AOR, 6.4; 95% CI, 1.2-32.8; p = 0.010) and ISS of greater than 15 (AOR, 2.5; 95% CI, 1.1-5.9; p = 0.037). Our study identifies independent risk factors associated with failure to achieve primary fascial closure during initial hospitalization after OA use for trauma. Additional study is required to validate appropriate algorithms that optimize the opportunity to achieve primary fascial closure and outcomes in this population. Prognostic study, level III.

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson’s disease

PubMed Central

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-01-01

AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson’s disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl- channel blocker diphenylamine-2, 2’-dicarboxylic acid, basolateral application of Na+-K+-2Cl-co-transporter antagonist bumetanide, elimination of Cl- from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl- secretion in the PD rat. PMID:25834315

Proteasome activity is important for replication recovery, CHK1 phosphorylation and prevention of G2 arrest after low-dose formaldehyde

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ortega-Atienza, Sara; Green, Samantha E.; Zhitkovich, Anatoly, E-mail: anatoly_zhitkovich@brown.edu

2015-07-15

Formaldehyde (FA) is a human carcinogen with numerous sources of environmental and occupational exposures. This reactive aldehyde is also produced endogenously during metabolism of drugs and other processes. DNA–protein crosslinks (DPCs) are considered to be the main genotoxic lesions for FA. Accumulating evidence suggests that DPC repair in high eukaryotes involves proteolysis of crosslinked proteins. Here, we examined a role of the main cellular proteolytic machinery proteasomes in toxic responses of human lung cells to low FA doses. We found that transient inhibition of proteasome activity increased cytotoxicity and diminished clonogenic viability of FA-treated cells. Proteasome inactivation exacerbated suppressive effectsmore » of FA on DNA replication and increased the levels of the genotoxic stress marker γ-H2AX in normal human cells. A transient loss of proteasome activity in FA-exposed cells also caused delayed perturbations of cell cycle, which included G2 arrest and a depletion of S-phase populations at FA doses that had no effects in control cells. Proteasome activity diminished p53-Ser15 phosphorylation but was important for FA-induced CHK1 phosphorylation, which is a biochemical marker of DPC proteolysis in replicating cells. Unlike FA, proteasome inhibition had no effect on cell survival and CHK1 phosphorylation by the non-DPC replication stressor hydroxyurea. Overall, we obtained evidence for the importance of proteasomes in protection of human cells against biologically relevant doses of FA. Biochemically, our findings indicate the involvement of proteasomes in proteolytic repair of DPC, which removes replication blockage by these highly bulky lesions. - Highlights: • Proteasome inhibition enhances cytotoxicity of low-dose FA in human lung cells. • Active proteasomes diminish replication-inhibiting effects of FA. • Proteasome activity prevents delayed G2 arrest in FA-treated cells. • Proteasome inhibition exacerbates replication stress by FA in normal human cells. • Protective role of proteasomes is linked to repair of DNA–protein crosslinks.« less

Introducing a non-pixelated and fast centre of mass detector for differential phase contrast microscopy.

PubMed

Schwarzhuber, Felix; Melzl, Peter; Pöllath, Simon; Zweck, Josef

2018-06-10

With the advent of probe corrected STEM machines it became possible to probe specimens on a scale of less than 50 pm resolution. This opens completely new horizons for research, as it is e.g. possible to probe the electrostatic fields between individual rows of atoms, using differential phase contrast (DPC). However, in contrast to conventional DPC, where one deals with extended fields which can be assumed constant across the electron probe, this is not possible for sub-atomic probes in DPC. For the latter case it was shown [1,2], that the strongly inhomogeneous field distribution within the probe diameter, which usually is caused by the nuclear potentials of an atomic column, leads to a complicated intensity redistribution within the diffraction disk. The task is then to determine the intensity weighted centre of the diffraction disk pattern (frequently also called centre of mass, COM), which is proportional to the average lateral momentum gained by the average electron, transmitted through the probe diameter. In first reported measurements, the determination of this COM was achieved using a pixelated detector in combination with a software-based evaluation of the COM. This suffers from two disadvantages: first, the nowadays available pixelated detectors are still not very fast (approximately 1000 fps) and quite expensive, and second, the amount of data to be processed after acquisition is comparatively huge. In this paper we report on an alternative to a pixelated detector, which is able to directly deliver the COM of a diffraction disk's intensity distribution with frequencies up to 200 kHz. We present measurements on the sensitivity of this detector as well as first results from DPC imaging. From these results we expect the detector also to serve well in sub-atomic DPC field sensing, possibly replacing today's segmented or pixelated detectors. Copyright © 2018 Elsevier B.V. All rights reserved.

A method to detect diphenylamine contamination of apple fruit and storages using headspace solid phase micro-extraction and gas chromatography/mass spectroscopy.

PubMed

Song, Jun; Forney, Charles F; Jordan, Michael A

2014-10-01

Analysis of headspace concentrations of diphenylamine using solid phase micro-extraction (SPME) was examined for its suitability to detect DPA contamination and off-gassing in apple (Malus domestica) fruit, storage rooms and storage materials. Four SPME fibre coatings including polydimethylsiloxane (PDMS, 100 μm), PDMS/divinylbenzene (PDMS/DVB), Polyacrylate (PA) and PDMS 7 μm were evaluated. The average limits of detection and of quantification for head space DPA ranged from 0.13 to 0.72 μg L(-1) and 0.42 to 2.35 μg L(-1), respectively. Polyacrylate was identified to be the most suitable and compatible fibre for DPA analysis in apple samples, because of its high sensitivity to DPA and low fruit volatile interferences. SPME techniques were further applied to study contamination of DPA in apples, storage rooms and packaging materials. DPA was found in the air of storage rooms containing apples that were not treated with DPA. Wood and plastic bin material, bin liners, and foam insulation all adsorbed and off-gassed DPA and could be potential sources of contamination of untreated apples. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Validity of diagnoses, procedures, and laboratory data in Japanese administrative data.

PubMed

Yamana, Hayato; Moriwaki, Mutsuko; Horiguchi, Hiromasa; Kodan, Mariko; Fushimi, Kiyohide; Yasunaga, Hideo

2017-10-01

Validation of recorded data is a prerequisite for studies that utilize administrative databases. The present study evaluated the validity of diagnoses and procedure records in the Japanese Diagnosis Procedure Combination (DPC) data, along with laboratory test results in the newly-introduced Standardized Structured Medical Record Information Exchange (SS-MIX) data. Between November 2015 and February 2016, we conducted chart reviews of 315 patients hospitalized between April 2014 and March 2015 in four middle-sized acute-care hospitals in Shizuoka, Kochi, Fukuoka, and Saga Prefectures and used them as reference standards. The sensitivity and specificity of DPC data in identifying 16 diseases and 10 common procedures were identified. The accuracy of SS-MIX data for 13 laboratory test results was also examined. The specificity of diagnoses in the DPC data exceeded 96%, while the sensitivity was below 50% for seven diseases and variable across diseases. When limited to primary diagnoses, the sensitivity and specificity were 78.9% and 93.2%, respectively. The sensitivity of procedure records exceeded 90% for six procedures, and the specificity exceeded 90% for nine procedures. Agreement between the SS-MIX data and the chart reviews was above 95% for all 13 items. The validity of diagnoses and procedure records in the DPC data and laboratory results in the SS-MIX data was high in general, supporting their use in future studies. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Gallium nitride based logpile photonic crystals.

PubMed

Subramania, Ganapathi; Li, Qiming; Lee, Yun-Ju; Figiel, Jeffrey J; Wang, George T; Fischer, Arthur J

2011-11-09

We demonstrate a nine-layer logpile three-dimensional photonic crystal (3DPC) composed of single crystalline gallium nitride (GaN) nanorods, ∼100 nm in size with lattice constants of 260, 280, and 300 nm with photonic band gap in the visible region. This unique GaN structure is created through a combined approach of a layer-by-layer template fabrication technique and selective metal organic chemical vapor deposition (MOCVD). These GaN 3DPC exhibit a stacking direction band gap characterized by strong optical reflectance between 380 and 500 nm. By introducing a "line-defect" cavity in the fifth (middle) layer of the 3DPC, a localized transmission mode with a quality factor of 25-30 is also observed within the photonic band gap. The realization of a group III nitride 3DPC with uniform features and a band gap at wavelengths in the visible region is an important step toward realizing complete control of the electromagnetic environment for group III nitride based optoelectronic devices.

Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

PubMed

Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G; Cryan, John F; Ross, R Paul; Quigley, Eamonn M; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F; O'Toole, Paul W; Stanton, Catherine

2012-01-01

The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.

Bifidobacterium breve with α-Linolenic Acid and Linoleic Acid Alters Fatty Acid Metabolism in the Maternal Separation Model of Irritable Bowel Syndrome

PubMed Central

Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G.; Cryan, John F.; Ross, R. Paul; Quigley, Eamonn M.; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F.; O'Toole, Paul W.; Stanton, Catherine

2012-01-01

The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (109 microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals. PMID:23185248

Convection vortex at dayside of high latitude ionosphere

NASA Astrophysics Data System (ADS)

Alexeev, I. I.; Feldstein, Y. I.; Greenwald, R. A.

Investigation of mesoscale convection in the dayside sector by SuperDARN radars has revealed the existence in afternoon sector a convection vortex whose location, intensity and convection direction coincide with the polar cap geomagnetic disturbances (DPC), which is reviewed thoroughly. Possible mechanism of the DPC generation are also described. Importance of the Earth's co-rotation potential is discussed. The existence of DPC vortex is interpreted in the framework of three dimensional current system with the field-aligned currents of coaxial cable type. In the vortex focus, the current outflowing from the ionosphere is concentrated whereas the inflowing current is distributed along the current system periphery.

3D algebraic iterative reconstruction for cone-beam x-ray differential phase-contrast computed tomography.

PubMed

Fu, Jian; Hu, Xinhua; Velroyen, Astrid; Bech, Martin; Jiang, Ming; Pfeiffer, Franz

2015-01-01

Due to the potential of compact imaging systems with magnified spatial resolution and contrast, cone-beam x-ray differential phase-contrast computed tomography (DPC-CT) has attracted significant interest. The current proposed FDK reconstruction algorithm with the Hilbert imaginary filter will induce severe cone-beam artifacts when the cone-beam angle becomes large. In this paper, we propose an algebraic iterative reconstruction (AIR) method for cone-beam DPC-CT and report its experiment results. This approach considers the reconstruction process as the optimization of a discrete representation of the object function to satisfy a system of equations that describes the cone-beam DPC-CT imaging modality. Unlike the conventional iterative algorithms for absorption-based CT, it involves the derivative operation to the forward projections of the reconstructed intermediate image to take into account the differential nature of the DPC projections. This method is based on the algebraic reconstruction technique, reconstructs the image ray by ray, and is expected to provide better derivative estimates in iterations. This work comprises a numerical study of the algorithm and its experimental verification using a dataset measured with a three-grating interferometer and a mini-focus x-ray tube source. It is shown that the proposed method can reduce the cone-beam artifacts and performs better than FDK under large cone-beam angles. This algorithm is of interest for future cone-beam DPC-CT applications.

Pre-synaptic glycine GlyT1 transporter--NMDA receptor interaction: relevance to NMDA autoreceptor activation in the presence of Mg2+ ions.

PubMed

Musante, Veronica; Summa, Maria; Cunha, Rodrigo A; Raiteri, Maurizio; Pittaluga, Anna

2011-05-01

Rat hippocampal glutamatergic terminals possess NMDA autoreceptors whose activation by low micromolar NMDA elicits glutamate exocytosis in the presence of physiological Mg(2+) (1.2 mM), the release of glutamate being significantly reduced when compared to that in Mg(2+)-free condition. Both glutamate and glycine were required to evoke glutamate exocytosis in 1.2 mM Mg(2+), while dizocilpine, cis-4-[phosphomethyl]-piperidine-2-carboxylic acid and 7-Cl-kynurenic acid prevented it, indicating that occupation of both agonist sites is needed for receptor activation. D-serine mimicked glycine but also inhibited the NMDA/glycine-induced release of [(3H]D-aspartate, thus behaving as a partial agonist. The NMDA/glycine-induced release in 1.2 mM Mg(2+) strictly depended on glycine uptake through the glycine transporter type 1 (GlyT1), because the GlyT1 blocker N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine hydrochloride, but not the GlyT2 blocker Org 25534, prevented it. Accordingly, [(3)H]glycine was taken up during superfusion, while lowering the external concentration of Na(+), the monovalent cation co-transported with glycine by GlyT1, abrogated the NMDA-induced effect. Western blot analysis of subsynaptic fractions confirms that GlyT1 and NMDA autoreceptors co-localize at the pre-synaptic level, where GluN3A subunits immunoreactivity was also recovered. It is proposed that GlyT1s coexist with NMDA autoreceptors on rat hippocampal glutamatergic terminals and that glycine taken up by GlyT1 may permit physiological activation of NMDA pre-synaptic autoreceptors. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Characterization of a bovine isolate Lactobacillus mucosae DPC 6426 which produces an exopolysaccharide composed predominantly of mannose residues

USDA-ARS?s Scientific Manuscript database

Aim: Identification of exopolysaccharide (EPS)-producing lactobacilli as EPS production is potentially a very important trait among probiotic lactobacilli from technological and health promoting perspectives. Methods and Results: Characterization of EPS-producing Lactobacillus mucosae DPC 6426 in de...

77 FR 38338 - Dairyland Power Cooperative; La Crosse Boiling Water Reactor Exemption From Certain Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... used.'' In 10 CFR 73.55, entitled ``Requirements for physical protection of licensed activities in...-shutdown decommissioning activities report (PSDAR). The DPC has been conducting dismantlement and decommissioning activities. The DPC is developing an onsite independent spent fuel storage installation (ISFSI...

77 FR 38339 - Dairyland Power Cooperative, La Crosse Boiling Water Reactor Exemption From Certain Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... intruders and ensure the integrity of physical barriers or other components and functions of the onsite... decommissioning plan is considered in the post-shutdown decommissioning activities report (PSDAR). The DPC has been conducting dismantlement and decommissioning activities. The DPC is developing an onsite...

Menaquinone-7 production from maize meal hydrolysate by Bacillus isolates with diphenylamine and analogue resistance* #

PubMed Central

Xu, Jian-zhong; Zhang, Wei-guo

2017-01-01

A menaquinone-7 (MK-7) high-producing strain needs to be isolated to increase MK-7 production, in order to meet a requirement of MK-7 given the low MK-7 content in food products. This article focuses on developing MK-7 high-producing strains via screening and mutagenesis by an atmospheric and room temperature plasma (ARTP) mutation breeding system. We isolated an MK-7-producing strain Y-2 and identified it as Bacillus amyloliquefaciens, which produced (7.1±0.5) mg/L of MK-7 with maize meal hydrolysate as carbon source. Then, an MK-7 high-producing strain B. amyloliquefaciens H.β.D.R.-5 with resistance to 1-hydroxy-2-naphthoic acid, β-2-thienylalanine, and diphenylamine was obtained from the mutation of the strain Y-2 using an ARTP mutation breeding system. Using strain H.β.D.R.-5, efficient production of MK-7 was achieved ((30.2±2.7) mg/L). In addition, the effects of nitrogen sources, prenyl alcohols, and MgSO4 on MK-7 production were investigated, suggesting that soymeal extract combined with yeast extract, isopentenol, and MgSO4 was beneficial. Under the optimized condition, the MK-7 production and biomass-specific yield reached (61.3±5.2) mg/L and 2.59 mg/L per OD600 unit respectively in a 7-L fermenter. These results demonstrated that strain H.β.D.R.-5 has the capacity to produce MK-7 from maize meal hydrolysate, which could reduce the substrate cost. PMID:28585422

Reassessment of the Unique Mode of Binding between Angiotensin II Type 1 Receptor and Their Blockers

PubMed Central

Matsuo, Yoshino; Saku, Keijiro; Karnik, Sadashiva S.

2013-01-01

While the molecular structures of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are very similar, they are also slightly different. Although each ARB has been shown to exhibit a unique mode of binding to AT1 receptor, different positions of the AT1 receptor have been analyzed and computational modeling has been performed using different crystal structures for the receptor as a template and different kinds of software. Therefore, we systematically analyzed the critical positions of the AT1 receptor, Tyr113, Tyr184, Lys199, His256 and Gln257 using a mutagenesis study, and subsequently performed computational modeling of the binding of ARBs to AT1 receptor using CXCR4 receptor as a new template and a single version of software. The interactions between Tyr113 in the AT1 receptor and the hydroxyl group of olmesartan, between Lys199 and carboxyl or tetrazole groups, and between His256 or Gln257 and the tetrazole group were studied. The common structure, a tetrazole group, of most ARBs similarly bind to Lys199, His256 and Gln257 of AT1 receptor. Lys199 in the AT1 receptor binds to the carboxyl group of EXP3174, candesartan and azilsartan, whereas oxygen in the amidecarbonyl group of valsartan may bind to Lys199. The benzimidazole portion of telmisartan may bind to a lipophilic pocket that includes Tyr113. On the other hand, the n-butyl group of irbesartan may bind to Tyr113. In conclusion, we confirmed that the slightly different structures of ARBs may be critical for binding to AT1 receptor and for the formation of unique modes of binding. PMID:24260317

Adenovirus-vectored shRNAs targeted to the highly conserved regions of VP1 and 2B in tandem inhibits replication of foot-and-mouth disease virus both in vitro and in vivo.

PubMed

Xu, Yan-Fang; Shen, Hai-Yan; Zhao, Ming-Qiu; Chen, Li-Jun; Li, Yin-Guang; Liao, Ming; Jia, Jun-Tao; Lv, Ying-Ran; Yi, Lin; Chen, Jin-Ding

2012-04-01

Foot-and-mouth disease is a highly contagious and economically important disease of cloven-hoofed animals. RNA interference (RNAi) can be used as a rapid and specific antiviral approach. It was shown that treatment with recombinant adenovirus (Ad(VP1-2B)) carrying shRNAs targeted to the VP1 and 2B genes of FMDV expressed in tandem had marked antiviral effects against FMDV both in IBRS-2 cells and guinea pigs. Treatment with Ad(VP1-2B) both before and after FMDV infection was most effective in IBRS-2 cells, as the FMDV RNA transcripts could not be detected within 48 h post-challenge (hpc), and the viral RNA copy number at 72 hpc was only 0.02% of that in the positive control group. Delivery of Ad(VP1-2B) reduced significantly the susceptibility of guinea pigs to FMDV infection. All guinea pigs were protected within 3 days post challenge (dpc) when they were injected twice with the same dose of Ad(VP1-2B), and a third treatment with the same dose of Ad(VP1-2B) at 3 dpc was necessary to confer longer lasting protection (up to 6 dpc). In conclusion, application of such a adenovirus vector to inhibit more than one viral gene may be an advantageous method for prevention and therapy of FMDV infection. Copyright © 2012 Elsevier B.V. All rights reserved.

Outcomes of different vital pulp therapy techniques on symptomatic permanent teeth: a case series.

PubMed

Asgary, Saeed; Fazlyab, Mahta; Sabbagh, Sedigheh; Eghbal, Mohammad Jafar

2014-01-01

In modern endodontics, vital pulp therapy (VPT) has been considered an ultra-conservative treatment modality. Based on the level of pulp preservation, VPT includes stepwise excavation, indirect pulp capping (IDPC), direct pulp capping (DPC), miniature pulpotomy (MP), partial/Cvek pulpotomy and coronal/complete pulpotomy (CP). The present article reviews the treatment outcomes of 94 permanent teeth with irreversible pulpitis treated with either IDPC (n=28), DPC (n=28), MP (n=29) or CP (n=9) using calcium-enriched mixture (CEM) cement. After a mean follow-up time of 12.3 months, 93 treated teeth were radiographic/clinically successful; only one radiographic failure was observed in the DPC group.

Outcomes of Different Vital Pulp Therapy Techniques on Symptomatic Permanent Teeth: A Case Series

PubMed Central

Asgary, Saeed; Fazlyab, Mahta; Sabbagh, Sedigheh; Eghbal, Mohammad Jafar

2014-01-01

In modern endodontics, vital pulp therapy (VPT) has been considered an ultra-conservative treatment modality. Based on the level of pulp preservation, VPT includes stepwise excavation, indirect pulp capping (IDPC), direct pulp capping (DPC), miniature pulpotomy (MP), partial/Cvek pulpotomy and coronal/complete pulpotomy (CP). The present article reviews the treatment outcomes of 94 permanent teeth with irreversible pulpitis treated with either IDPC (n=28), DPC (n=28), MP (n=29) or CP (n=9) using calcium-enriched mixture (CEM) cement. After a mean follow-up time of 12.3 months, 93 treated teeth were radiographic/clinically successful; only one radiographic failure was observed in the DPC group. PMID:25386213

Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota.

PubMed

Wall, Rebecca; Marques, Tatiana M; O'Sullivan, Orla; Ross, R Paul; Shanahan, Fergus; Quigley, Eamonn M; Dinan, Timothy G; Kiely, Barry; Fitzgerald, Gerald F; Cotter, Paul D; Fouhy, Fiona; Stanton, Catherine

2012-05-01

We previously showed that microbial metabolism in the gut influences the composition of bioactive fatty acids in host adipose tissue. This study compared the effect of dietary supplementation for 8 wk with human-derived Bifidobacterium breve strains on fat distribution and composition and the composition of the gut microbiota in mice. C57BL/6 mice (n = 8 per group) received B. breve DPC 6330 or B. breve NCIMB 702258 (10(9) microorganisms) daily for 8 wk or no supplement (controls). Tissue fatty acid composition was assessed by gas-liquid chromatography while 16S rRNA pyrosequencing was used to investigate microbiota composition. Visceral fat mass and brain stearic acid, arachidonic acid, and DHA were higher in mice supplemented with B. breve NCIMB 702258 than in mice in the other 2 groups (P < 0.05). In addition, both B. breve DPC 6330 and B. breve NCIMB 702258 supplementation resulted in higher propionate concentrations in the cecum than did no supplementation (P < 0.05). Compositional sequencing of the gut microbiota showed a tendency for greater proportions of Clostridiaceae (25%, 12%, and 18%; P = 0.08) and lower proportions of Eubacteriaceae (3%, 12%, and 13%; P = 0.06) in mice supplemented with B. breve DPC 6330 than in mice supplemented with B. breve NCIMB 702258 and unsupplemented controls, respectively. The response of fatty acid metabolism to administration of bifidobacteria is strain-dependent, and strain-strain differences are important factors that influence modulation of the gut microbial community by ingested microorganisms.

A study on mastectomy samples to evaluate breast imaging quality and potential clinical relevance of differential phase contrast mammography.

PubMed

Hauser, Nik; Wang, Zhentian; Kubik-Huch, Rahel A; Trippel, Mafalda; Singer, Gad; Hohl, Michael K; Roessl, Ewald; Köhler, Thomas; van Stevendaal, Udo; Wieberneit, Nataly; Stampanoni, Marco

2014-03-01

Differential phase contrast and scattering-based x-ray mammography has the potential to provide additional and complementary clinically relevant information compared with absorption-based mammography. The purpose of our study was to provide a first statistical evaluation of the imaging capabilities of the new technique compared with digital absorption mammography. We investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using grating-based differential phase contrast mammography (mammoDPC) with a conventional, low-brilliance x-ray tube. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into novel high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a 2-part blinded, prospective independent reader study. The results were statistically analyzed in terms of image quality and clinical relevance. The results of the comparison of mammoDPC with clinical digital mammography revealed the general quality of the images to be significantly superior (P < 0.001); sharpness, lesion delineation, as well as the general visibility of calcifications to be significantly more assessable (P < 0.001); and delineation of anatomic components of the specimens (surface structures) to be significantly sharper (P < 0.001). Spiculations were significantly better identified, and the overall clinically relevant information provided by mammoDPC was judged to be superior (P < 0.001). Our results demonstrate that complementary information provided by phase and scattering enhanced mammograms obtained with the mammoDPC approach deliver images of generally superior quality. This technique has the potential to improve radiological breast diagnostics.

Photophysical and electrochemical investigation of highly conjugated pyridine based diphenylamine materials

NASA Astrophysics Data System (ADS)

Mahesh, K.; Priyanka, V.; Vijai Anand, A. S.; Karpagam, S.

2018-02-01

Three simple and small donor-acceptor type conjugated moieties, namely (2Z, 2‧Z)-3,3'-((hexylazanediyl)bis (4,1-phenylene))bis (2-(pyridin-2-yl)acrylonitrile) (DPA-PA-1), (2Z, 2‧Z)-3,3'-((dodecylazanediyl)bis (4,1-phenylene))bis (2-(pyridin-2-yl)acrylonitrile) (DPA-PA-2), (2Z,2‧Z)-3,3'-((allylazanediyl)bis (4,1-phenylene))bis (2-(pyridin-2-yl)acrylonitrile) DPA-PA-3 have been synthesized according to the Knoevenagel condensation. Here alkyl (hexyl, dodecyl, allyl) diphenylamine (DPA) moieties acts as an electron donor and pyridine-acetonitrile (PA) moiety acts as an electron acceptor. These moieties are recently showing great interest in optoelectronic applications. The structures of the DPA-PA-1-3 were confirmed by FT-IR, 1H NMR and 13C NMR. The final products showed great solubility in common organic solvents such as toluene, tetrahydrofuran, ethyl acetate, dichloromethane, chloroform etc due to the alkyl chains. The absorption maximum of DPA-PA-1-3 appeared at 440, 433, 447 nm in chloroform solution. The optical band gaps are 2.33, 2.29, and 2.25 eV calculated from thin film absorption edges. The photoluminescence spectra of three molecules were exhibited a maximum peak at 511, 513, 529 nm with greenish fluorescence in chloroform solution and 553, 541, 554 nm as in thin film state. DPA-PA-1-3 showed a delay fluorescence decay time (τ1) of 35, 16 and 14 μs respectively. The lower electrochemical band gaps 1.90 and 1.80 eV was observed by cyclic voltammetry. The morphological images were indicated that spherical shaped particles were observed with lower surface roughness. These types of low bandgap materials have much attention for their various potential applications in optoelectronic devices.

Tetracoordinate Imidazole-Based Boron Complexes for the Selective Detection of Picric Acid.

PubMed

Dhanunjayarao, Kunchala; Mukundam, Vanga; Venkatasubbaiah, Krishnan

2016-11-07

N,N-Dimethylamine and N,N-diphenylamine-decorated highly fluorescent imidazole borates have been synthesized and investigated as new fluorophores for the selective detection of trinitrophenol/picric acid (PA). Structural studies of a probe 1 and PA (1·PA) complex revealed that the adduct formed by the deprotonation of PA by the -NMe 2 group along with weak interactions is responsible for the selective detection of PA over other polynitrated organic compounds.

Solid Phase Extraction of Trace Elements in Waterand Tissue Samples on a Mini Column with Diphenylcarbazone Impregnated Nano-TiO2 and Their Determination by Inductively Coupled Plasma Optical Emission Spectrometry

PubMed Central

Baytak, Sıtkı; Arslan, Zikri

2015-01-01

This study presents a simple, robust and environmentally friendly solid phase preconcentration procedure for multielement determination by inductively coupled plasma optical emission spectrometry (ICP-OES) using diphenylcarbazone (DPC) impregnated TiO2 nanopowder (n-TiO2). DPC was successfully impregnated onto n-TiO2 in colloidal solution. A number of elements, including Co(II), Cr(III), Cu(II), Fe(III), Mn(II) and Zn(II) were quantitatively preconcentrated from aqueous solutions between pH 8 and 8.5 at a flow rate of 2 mL min−1, and then eluted with 2 mL of 5% (v/v) HNO3. A mini-column packed with 0.12 g DPC impregnated n-TiO2 retained all elements quantitatively from up to 250 mL multielement solution (2.5 μg per analyte) affording an enrichment factor of 125. The limits of detection (LOD) for preconcentration of 50 mL blank solutions (n = 12) were 0.28, 0.15, 0.25, 0.22, 0.12, and 0.10 μg L−1 for Co, Cr, Cu, Fe, Mn, and Zn, respectively. The relative standard deviation (RSD) for five replicate determinations was 0.8, 3.4, 2.6, 2.2, 1.2 and 3.3% for Co, Cr, Cu, Fe, Mn and Zn, respectively, at 5 μg L−1 level. The method was validated with analysis of Freshwater (SRM 1643e) and Lobster hepatopancreas (TORT-2) certified reference materials, and then applied to the determination of the elements from tap water and lake water samples by ICP-OES. PMID:26236403

Reverse matrix converter control method for PMSM drives using DPC

NASA Astrophysics Data System (ADS)

Bak, Yeongsu; Lee, Kyo-Beum

2018-05-01

This paper proposes a control method for a reverse matrix converter (RMC) that drives a three-phase permanent magnet synchronous motor (PMSM). In this proposed method, direct power control (DPC) is used to control the voltage source rectifier of the RMC. The RMC is an indirect matrix converter operating in the boost mode, in which the power-flow directions of the input and output are switched. It has a minimum voltage transfer ratio of 1/0.866 in a linear-modulation region. In this paper, a control method that uses DPC as an additional control method is proposed in order to control the RMC driving a PMSM in the output stage. Simulations and experimental results verify the effectiveness of the proposed control method.

Improving the efficiency and directivity of THz photoconductive antennas by using a defective photonic crystal substrate

NASA Astrophysics Data System (ADS)

Rahmati, Ehsan; Ahmadi-Boroujeni, Mehdi

2018-04-01

One of the shortcomings of photoconductive (PC) antennas in terahertz (THz) generation is low effective radiated power in the desirable direction. In this paper, we propose a defective photonic crystal (DPC) substrate consisting of a customized 2D array of air holes drilled into a solid substrate in order to improve the radiation characteristics of THz PC antennas. The effect of the proposed structure on the performance of a conventional THz PC antenna has been examined from several aspects including radiation efficiency, directivity, and field distribution. By comparing the radiation performance of the THz antenna on the proposed DPC substrate to that of the conventional solid substrate, it is shown that the proposed technique can significantly improve the efficiency and directivity of the THz PC antenna over a wide frequency range. It is achieved by reducing the amount of power coupled to the substrate surface waves and limiting the radiation in undesirable directions. In addition, it is found that the sensitivity of directivity to the substrate thickness is considerably decreased and the adverse Fabry-Perot effects of the thick substrate are reduced by the application of the proposed DPC substrate.

CALIPSO Data Products Catalog

Atmospheric Science Data Center

2013-11-12

... layer base temperature The parameter "single shot cloud cleared fraction" was added to Lidar Level 2 5-km cloud and aerosol ... convention. Adjusted spacing for content to fit on one page.   DPC Release 2.4 PDF: Size ~3 MB December 2007 ...

40 CFR 180.190 - Diphenylamine; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Cattle, fat 0.01 Cattle, liver 0.1 Cattle, meat byproducts, except liver 0.01 Cattle, meat 0.01 Goat, fat 0.01 Goat, liver 0.1 Goat, meat byproducts, except liver 0.01 Goat, meat 0.01 Horse, fat 0.01 Horse...

Novel conjugative plasmids from the natural isolate Lactococcus lactis subspecies cremoris DPC3758: a repository of genes for the potential improvement of dairy starters.

PubMed

Fallico, V; Ross, R P; Fitzgerald, G F; McAuliffe, O

2012-07-01

A collection of 17 natural lactococcal isolates from raw milk cheeses were studied in terms of their plasmid distribution, content, and diversity. All strains in the collection harbored an abundance of plasmids, including Lactococcus lactis ssp. cremoris DPC3758, whose 8-plasmid complement was selected for sequencing. The complete sequences of pAF22 (22,388 kb), pAF14 (14,419 kb), pAF12 (12,067 kb), pAF07 (7,435 kb), and pAF04 (3,801 kb) were obtained, whereas gene functions of technological interest were mapped to pAF65 (65 kb) and pAF45 (45 kb) by PCR. The plasmids of L. lactis DPC3758 were found to encode many genes with the potential to improve the technological properties of dairy starters. These included 3 anti-phage restriction/modification (R/M) systems (1 of type I and 2 of type II) and genes for immunity/resistance to nisin, lacticin 481, cadmium, and copper. Regions encoding conjugative/mobilization functions were present in 6 of the 8 plasmids, including those containing the R/M systems, thus enabling the food-grade transfer of these mechanisms to industrial strains. Using cadmium selection, the sequential stacking of the R/M plasmids into a plasmid-free host provided the recipient with increased protection against 936- and c2-type phages. The association of food-grade selectable markers and mobilization functions on L. lactis DPC3758 plasmids will facilitate their exploitation to obtain industrial strains with enhanced phage protection and robustness. These natural plasmids also provide another example of the major role of plasmids in contributing to host fitness and preservation within its ecological niche. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

Grid Resolution Study over Operability Space for a Mach 1.7 Low Boom External Compression Inlet

NASA Technical Reports Server (NTRS)

Anderson, Bernhard H.

2014-01-01

This paper presents a statistical methodology whereby the probability limits associated with CFD grid resolution of inlet flow analysis can be determined which provide quantitative information on the distribution of that error over the specified operability range. The objectives of this investigation is to quantify the effects of both random (accuracy) and systemic (biasing) errors associated with grid resolution in the analysis of the Lockheed Martin Company (LMCO) N+2 Low Boom external compression supersonic inlet. The study covers the entire operability space as defined previously by the High Speed Civil Transport (HSCT) High Speed Research (HSR) program goals. The probability limits in terms of a 95.0% confidence interval on the analysis data were evaluated for four ARP1420 inlet metrics, namely (1) total pressure recovery (PFAIP), (2) radial hub distortion (DPH/P), (3) ) radial tip distortion (DPT/P), and (4) ) circumferential distortion (DPC/P). In general, the resulting +/-0.95 delta Y interval was unacceptably large in comparison to the stated goals of the HSCT program. Therefore, the conclusion was reached that the "standard grid" size was insufficient for this type of analysis. However, in examining the statistical data, it was determined that the CFD analysis results at the outer fringes of the operability space were the determining factor in the measure of statistical uncertainty. Adequate grids are grids that are free of biasing (systemic) errors and exhibit low random (precision) errors in comparison to their operability goals. In order to be 100% certain that the operability goals have indeed been achieved for each of the inlet metrics, the Y+/-0.95 delta Y limit must fall inside the stated operability goals. For example, if the operability goal for DPC/P circumferential distortion is =0.06, then the forecast Y for DPC/P plus the 95% confidence interval on DPC/P, i.e. +/-0.95 delta Y, must all be less than or equal to 0.06.

Diffuse thyroid uptake incidentally found on 18F-fluorodeoxyglucose positron emission tomography in subjects without cancer history.

PubMed

Lee, Ji Young; Choi, Joon Young; Choi, Yoon-Ho; Hyun, Seung Hyup; Moon, Seung Hwan; Jang, Su Jin; Choe, Yearn Seong; Lee, Kyung-Han; Kim, Byung-Tae

2013-01-01

We investigated the clinical significance of incidental diffuse thyroid uptake (DTU) on (18)F-FDG PET in subjects without a history of cancer. This study included 2062 studies from adults who underwent (18)F-FDG PET as a cancer screening program. Subjects were divided into the following two groups: with (group I) or without (group II) DTU. The presence of DTU and the thyroid visual grading score were compared with thyroid function tests, serum anti-microsomal antibody (AMA) levels, and the presence of diffuse parenchymal change (DPC) on ultrasonography (USG). DTU was found in 6.6% of the scans (137/2062). Serum thyroid stimulating hormone (TSH) and AMA levels were significantly higher in group I than in group II. Increased AMA level (55.1%) and DPC (48.7%) were more frequently found in group I (p < 0.001). The proportion of subjects with any abnormal results in serum free thyroxine, triiodothyronine, TSH, or AMA levels or DPC on USG was significantly higher in group I than in group II (71.5% vs. 10.6%, p < 0.001), and was significantly and gradually increased according to the visual grading score group (0 vs. 1-2 vs. 3-4 = 10.6% vs. 58.5% vs. 90.9%, p < 0.001). TSH and is AMA levels were significantly increased according to the visual grading score. The presence or degree of incidental DTU on (18)F-FDG PET is closely correlated with increased serum AMA and TSH levels, and the presence of DPC on USG. Therefore, the most plausible pathological cause of DTU may be cell damage by an autoimmune mechanism.

Expression and localization of collectins in feto-maternal tissues of human first trimester spontaneous abortion and abortion prone mouse model.

PubMed

Yadav, A K; Chaudhari, H; Shah, P K; Madan, T

2016-02-01

Dysregulation of immune response at the feto-maternal interface during first trimester of pregnancy is one of the leading causes of spontaneous abortion. Previously, we reported differential expression of collectins, soluble pattern recognition molecules involved in immunoregulation, in placental and decidual tissues during spontaneous labor. In the present pilot study, the expression of collectins was analyzed in the inflamed human gestational tissues of spontaneous abortion ('SA') and in 13.5 dpc placental tissues from resorption survived embryos of murine model (CBA/J X DBA/2J). Transcripts of SP-A were significantly down-regulated and SP-D were significantly up-regulated in placental and decidual tissues of 'SA' group compared to that of 'normal' group. Immunostaining for SP-D and MBL proteins was positive in placental and decidual tissues. However, levels of SP-D and MBL proteins were not significantly altered in placental as well as in decidual tissues of 'SA' group in comparison to the 'normal' group. Placental tissues of viable embryos from the abortion prone mouse model showed significantly enhanced expression of mSP-A and mSP-D transcripts at 13.5 day post coitus (dpc) and 14.5 dpc compared to the control group (CBA/J X Balb/c). Mouse collectins were localized in placental tissues (13.5 dpc), with increased staining in murine model compared to control. Human and murine data together indicate that SP-A, SP-D and MBL are synthesised in early gestational tissues, and may contribute to regulation of immune response at the feto-maternal interface during pregnancy. Copyright © 2015 Elsevier GmbH. All rights reserved.

Reduction of matrix effects and improvement of sensitivity during determination of two chloridazon degradation products in aqueous matrices by using UPLC-ESI-MS/MS.

PubMed

Kowal, Sebastian; Balsaa, Peter; Werres, Friedrich; Schmidt, Torsten C

2012-06-01

The development and validation of a sensitive and reliable detection method for the determination of two polar degradation products, desphenyl-chloridazon (DPC) and methyl-desphenyl-chloridazon (MDPC) in surface water, ground water and drinking water is presented. The method is based on direct large volume injection ultra-performance liquid chromatography electrospray tandem mass spectrometry. This simple but powerful analytical method for polar substances in the aquatic environment is usually hampered by varying matrix effects, depending on the nature of different water bodies. For the two examined degradation products, the matrix effects are particularly strong compared with other polar degradation products of pesticides. Therefore, matrix effects were studied thoroughly with the aim of minimising them and improving sensitivity during determination by postcolumn addition of ammonia solution as a modifier. An internal standard was used in order to compensate for remaining matrix effects. The calibration curve shows very good coefficients of correlation (0.9994 for DPC and 0.9999 for MDPC). Intraday precision values were lower than 5 % for DPC, 3 % for MDPC and the limits of detection were 10 ng/L for both substances. The method was successfully used in a national round robin test with a deviation between 3 and 8 % from target values. Finally, about 1,000 samples from different water bodies have been examined with this method in the Rhine and Ruhr region of North-Rhine-Westphalia (Germany) and in the European Union. Approximately 76 % of analysed samples contained measurable amounts of DPC at concentrations up to 8 μg/L while 53 % of the samples showed MDPC concentrations up to 2.3 μg/L.

Matrix isolation with an ion transfer device for interference-free simultaneous spectrophotometric determinations of hexavalent and trivalent chromium in a flow-based system.

PubMed

Ohira, Shin-Ichi; Nakamura, Koretaka; Chiba, Mitsuki; Dasgupta, Purnendu K; Toda, Kei

2017-03-01

Chromium speciation by spectrophotometric determination of hexavalent chromium (Cr(VI)) with diphenylcarbazide (DPC) has several problems. These include: (1) the inability to directly detect trivalent chromium (Cr(III)) with DPC, (2) positive interference in Cr(VI) determination by other metal cations and (3) negative interference by any reducing agent present in the sample. These are addressed with an ion transfer device (ITD) in a flow injection analysis system. We previously developed the ITD for electrodialytic separations. Here we separate oppositely charged Cr(III) and Cr(VI) species by the ITD into two different acceptor solutions within ~5 s. The acceptor solutions consist of buffered H 2 O 2 to oxidize the Cr(III) to Cr(VI). Then DPC is added to either acceptor to measure Cr(III) and Cr(VI) spectrophotometrically. The system was optimized to provide the same response for Cr(VI) and Cr(III) with limits of detection (LODs, S/N=3) of 0.5 μg L -1 for each and a throughput rate of 30 samples h -1 . The ITD separation was also effective for matrix isolation and reduction of interferences. Potential cationic interferences were not transferred into the anionic Cr(VI) acceptor stream. Much of the organic compounds in soil extracts were also eliminated as evidenced from standard addition and recovery studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy

PubMed Central

Allen, David G.; Whitehead, Nicholas P.; Froehner, Stanley C.

2015-01-01

Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca2+-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca2+ entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease. PMID:26676145

Spatial resolution characterization of differential phase contrast CT systems via modulation transfer function (MTF) measurements

NASA Astrophysics Data System (ADS)

Li, Ke; Zambelli, Joseph; Bevins, Nicholas; Ge, Yongshuai; Chen, Guang-Hong

2013-06-01

By adding a Talbot-Lau interferometer to a conventional x-ray absorption computed tomography (CT) imaging system, both differential phase contrast (DPC) signal and absorption contrast signal can be simultaneously measured from the same set of CT measurements. The imaging performance of such multi-contrast x-ray CT imaging systems can be characterized with standard metrics such as noise variance, noise power spectrum, contrast-to-noise ratio, modulation transfer function (MTF), and task-based detectability index. Among these metrics, the measurement of the MTF can be challenging in DPC-CT systems due to several confounding factors such as phase wrapping and the difficulty of using fine wires as probes. To address these technical challenges, this paper discusses a viable and reliable method to experimentally measure the MTF of DPC-CT. It has been found that the spatial resolution of DPC-CT is degraded, when compared to that of the corresponding absorption CT, due to the presence of a source grating G0 in the Talbot-Lau interferometer. An effective MTF was introduced and experimentally estimated to describe the impact of the Talbot-Lau interferometer on the system MTF.

Sampling and analysis of hexavalent chromium during exposure to chromic acid mist and welding fumes.

PubMed

Blomquist, G; Nilsson, C A; Nygren, O

1983-12-01

Sampling and analysis of hexavalent chromium during exposure to chromic acid mist and welding fumes. Scand j work environ & health 9 (1983) 489-495. In view of the serious health effects of hexavalent chromium, the problems involved in its sampling and analysis in workroom air have been the subject of much concern. In this paper, the stability problems arising from the reduction of hexavalent to trivalent chromium during sampling, sample storage, and analysis are discussed. Replacement of sulfuric acid by a sodium acetate buffer (pH 4) as a leaching solution prior to analysis with the diphenylcarbazide (DPC) method is suggested and is demonstrated to be necessary in order to avoid reduction. Field samples were taken from two different industrial processes-manual metal arc welding on stainless steel without shield gas and chromium plating. A comparison was made of the DPC method, acidic dissolution with atomic absorption spectrophotometric (AAS) analysis, and the carbonate method. For chromic acid mist, the DPC method and AAS analysis were shown to give the same results. In the analysis of welding fumes, the modified DPC method gave the same results as the laborious and less sensitive carbonate method.

ASSEMBLY TRANSFER SYSTEM DESCRIPTION DOCUMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

B. Gorpani

2000-06-26

The Assembly Transfer System (ATS) receives, cools, and opens rail and truck transportation casks from the Carrier/Cask Handling System (CCHS). The system unloads transportation casks consisting of bare Spent Nuclear Fuel (SNF) assemblies, single element canisters, and Dual Purpose Canisters (DPCs). For casks containing DPCs, the system opens the DPCs and unloads the SNF. The system stages the assemblies, transfer assemblies to and from fuel-blending inventory pools, loads them into Disposal Containers (DCs), temporarily seals and inerts the DC, decontaminates the DC and transfers it to the Disposal Container Handling System. The system also prepares empty casks and DPCs formore » off-site shipment. Two identical Assembly Transfer System lines are provided in the Waste Handling Building (WHB). Each line operates independently to handle the waste transfer throughput and to support maintenance operations. Each system line primarily consists of wet and dry handling areas. The wet handling area includes a cask transport system, cask and DPC preparation system, and a wet assembly handling system. The basket transport system forms the transition between the wet and dry handling areas. The dry handling area includes the dry assembly handling system, assembly drying system, DC preparation system, and DC transport system. Both the wet and dry handling areas are controlled by the control and tracking system. The system operating sequence begins with moving transportation casks to the cask preparation area. The cask preparation operations consist of cask cavity gas sampling, cask venting, cask cool-down, outer lid removal, and inner shield plug lifting fixture attachment. Casks containing bare SNF (no DPC) are filled with water and placed in the cask unloading pool. The inner shield plugs are removed underwater. For casks containing a DPC, the cask lid(s) is removed, and the DPC is penetrated, sampled, vented, and cooled. A DPC lifting fixture is attached and the cask is placed into the cask unloading pool. In the cask unloading pool the DPC is removed from the cask and placed in an overpack and the DPC lid is severed and removed. Assemblies are removed from either an open cask or DPC and loaded into assembly baskets positioned in the basket staging rack in the assembly unloading pool. A method called ''blending'' is utilized to load DCs with a heat output of less than 11.8 kW. This involves combining hotter and cooler assemblies from different baskets. Blending requires storing some of the hotter fuel assemblies in fuel-blending inventory pools until cooler assemblies are available. The assembly baskets are then transferred from the basket staging rack to the assembly handling cell and loaded into the assembly drying vessels. After drying, the assemblies are removed from the assembly drying vessels and loaded into a DC positioned below the DC load port. After installation of a DC inner lid and temporary sealing device, the DC is transferred to the DC decontamination cell where the top area of the DC, the DC lifting collar, and the DC inner lid and temporary sealing device are decontaminated, and the DC is evacuated and backfilled with inert gas to prevent prolonged clad exposure to air. The DC is then transferred to the Disposal Container Handling System for lid welding. In another cask preparation and decontamination area, lids are replaced on the empty transportation casks and DPC overpacks, the casks and DPC overpacks are decontaminated, inspected, and transferred to the Carrier/Cask Handling System for shipment off-site. All system equipment is designed to facilitate manual or remote operation, decontamination, and maintenance. The system interfaces with the Carrier/Cask Handling System for incoming and outgoing transportation casks and DPCs. The system also interfaces with the Disposal Container Handling System, which prepares the DC for loading and subsequently seals the loaded DC. The system support interfaces are the Waste Handling Building System and other internal WHB support systems.« less

21 CFR 177.1590 - Polyester elastomers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... alpha-hydroomega-hydroxypoly (oxytetramethylene) and/or 1,4-butanediol such that the finished elastomer... physical properties may include the following substances: List of substances Limitations 4,4′ - Bis (alpha, alpha-dimethyl-benzyl) diphenylamine For use only as an antioxidant. Tetrabutyl titanate For use only as...

NIST Efforts to Quality-Assure Gunpowder Measurements

NASA Technical Reports Server (NTRS)

MacCrehan, William A.; Reardon, Michelle R.

2000-01-01

In the past few years, the National Institute for Standards and Technology (NIST) has been promoting the idea of quantitatively determining the additives in smokeless gunpowder using micellar capillary electrophoresis as a means of investigating the criminal use of hand guns and pipe bombs. As a part of this effort, we have evaluated both supercritical fluid and ultrasonic solvent extractions for the quantitative recovery of nitroglycerin (NG), diphenylamine (DPA), N-nitrosodiphenylamine (NnDPA), and ethyl centralite (EC) from gunpowder. Recoveries were evaluated by repeat extraction and matrix spiking experiments. The final extraction protocol provides greater than 95 percent recoveries. To help other researches validate their own analytical method for additive determinations, NIST is exploring the development of a standard reference material, Additives in Smokeless Gunpowder. The evaluated method is being applied to two double-base (NG-containing) powders, one stabilized with diphenylamine and the other with ethyl centralite. As part of this reference material development effort, we are conducting an interlaboratory comparison exercise among the forensic and military gunpowder measurement community.

VizieR Online Data Catalog: Second Planck Catalogue of Compact Sources (PCCS2) (Planck+, 2016)

NASA Astrophysics Data System (ADS)

Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Argueso, F.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Bartolo, N.; Battaner, E.; Beichman, C.; Benabed, K.; Benoit, A.; Benoit-Levy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bock, J. J.; Bohringer, H.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Carvalho, P.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.-R.; Chiang, H. C.; Christensen, P. R.; Clemens, M.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; De Rosa, A.; de Zotti, G.; Delabrouille, J.; Desert, F.-X.; Dickinson, C.; Diego, J. M.; Dole, H.; Donzelli, S.; Dore, O.; Douspis, M.; Ducout, A.; Dupac, X.; Efstathiou, G.; Elsner, F.; Ensslin, T. A.; Eriksen, H. K.; Falgarone, E.; Fergusson, J.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Frejse, L. A.; Galeotta, S.; Galli, S.; Ganga, K.; Giard, M.; Giraud-Heraud, Y.; Gjerlow, E.; Gonzalez-Nuevo, J.; Gorski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Helou, G.; Henrot-Versille, S.; Hernandez-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huffenberger, K. M.; Hurier, G.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihanen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lahteenmaki, A.; Lamarre, J.-M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Leahy, J. P.; Leonardi, R.; Leon-Tavares, J.; Lesgourgues, J.; Levrier, F.; Liguori, M.; Lilje, P. B.; Linden-Vornle, M.; Lopez-Caniego, M.; Lubin, P. M.; Macias-Perez, J. F.; Maggio, G.; Maino, D.; Mandolesi, N.; Mangilli, A.; Maris, M.; Marshall, D. J.; Martin, P. G.; Martinez-Gonzalez, E.; Masi, S.; Matarrese, S.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschenes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Negrello, M.; Netterfield, C. B.; Norgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paladini, R.; Paoletti, D.; Partridge, B.; Pasian, F.; Patanchon, G.; Pearson, T. J.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Pratt, G. W.; Prezeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rossetti, M.; Roudier, G.; Rowan-Robinson, M.; Rubino-Martin, J. A.; Rusholme, B.; Sandri, M.; Sanghera, H. S.; Santos, D.; Savelainen, M.; Savini, G.; Scott, D.; Seiffert, M. D.; Shellard, E. P. S.; Spencer, L. D.; Stolyarov, V.; Sudiwala, R.; Sunyaev, R.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Torni Koski, M.; Tristram, M.; Tucci, M.; Tuovinen, J.; Turler, M.; Umana, G.; Valenziano, L.; Valiviita, J.; van Tent, B.; Vielva, P.; Villa, F.; Wade, L. A.; Walter, B.; Wandelt, B. D.; Wehus, I. K.; Yvon, D.; Zacchei, A.; Zonca, A.

2017-01-01

The Low Frequency Instrument (LFI) DPC produced the 30, 44, and 70GHz maps after the completion of eight full surveys (spanning the period 12 August 2009 to 3 August 2013). In addition, special LFI maps covering the period 1 April 2013 to 30 June 2013 were produced in order to compare the Planck flux-density scales with those of the Very Large Array and the Australia Telescope Compact Array, by performing simultaneous observations of a sample of sources over that period. The High Frequency Instrument (HFI) DPC produced the 100, 143, 217, 353, 545, and 857GHz maps after five full surveys (2009 August 12 to 2012 January 11). (16 data files).

MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice

PubMed Central

Risal, Sanjiv; Zhang, Jingjing; Adhikari, Deepak; Liu, Xiaoman; Shao, Jingchen; Hu, Mengwen; Busayavalasa, Kiran; Tu, Zhaowei; Chen, Zijiang; Kaldis, Philipp; Liu, Kui

2017-01-01

In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75–8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death of Mastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl-null PGCs was rescued by simultaneous deletion of Ppp2r1a (α subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis. PMID:28224044

Increased short circuit current in an azafullerene-based organic solar cell.

PubMed

Cambarau, Werther; Fritze, Urs F; Viterisi, Aurélien; Palomares, Emilio; von Delius, Max

2015-01-21

We report the synthesis of a solution-processable, dodecyloxyphenyl-substituted azafullerene monoadduct (DPC59N) and its application as electron acceptor in bulk heterojunction organic solar cells (BHJ-OSCs). Due to its relatively strong absorption of visible light, DPC59N outperforms PC60BM in respect to short circuit current (JSC) and external quantum efficiency (EQE) in blends with donor P3HT.

The classification of gunshot residue using laser electrospray mass spectrometry and offline multivariate statistical analysis

USDA-ARS?s Scientific Manuscript database

Nonresonant laser vaporization combined with high-resolution electrospray time-of-flight mass spectrometry enables analysis of a casing after discharge of a firearm revealing organic signature molecules including methyl centralite (MC), diphenylamine (DPA), N-nitrosodiphenylamine (N-NO-DPA), 4-nitro...

Experimental and molecular modeling investigation of isopropyl 4-(biphenyl-4-Yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

NASA Astrophysics Data System (ADS)

Yıldırım, Sema Öztürk; ćetin, Gökalp; Büyükmumcu, Zeki; Şimşek, Rahime; Şafak, Cihat; Butcher, Ray J.; Pekdur, Özlem Savaş

2018-02-01

The most important effect of 1,4-dihydropyridine (1,4-DHP) derivatives with various biological activities is to reduce the influx of extracellular Ca2+ ions. Because of this feature, many 1,4-DHP derivatives have been identified as potent calcium channel blockers and have been included in the treatment as antihypertensive agents. On the other hand, the biphenyl group is an important group in the molecule of biologically active compounds. The active compounds are obtained by introducing the biphenyl group into the structure of various compounds. In this study, the biphenyl group was introduced into the 1,4-DHP ring to reach to hexahydroquinoline (HHQ) derivative as an active calcium channel blocker compound. The structure of the compound was proved by IR, 1H-NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic properties of the compound has been determined, and biological activity assays continue. The crystal structure of C28H31NO3 was determined by single crystal X-ray diffraction: monoclinic, space group C c, a = 11.9713(3) Å, b = 18.7893(5) Å, c = 10.7358(3) Å, β = 102.411(4)°, Z = 4. The title molecule is twisted with the dihedral angle between two phenyl rings being 50.86(10)°. The optimized geometries of the title compound have been obtained employing DFT method. The calculated geometrical parameters were found to be in agreement with the experimental data.

Effects of ensiling cereal grains (barley, wheat, triticale and rye) on total and pre-caecal digestibility of proximate nutrients and amino acids in pigs.

PubMed

Hackl, W; Pieper, B; Pieper, R; Korn, U; Zeyner, A

2010-12-01

Inclemency of weather frequently causes critical water contents in cereal grains above 15%. Ensiling in pre-mature condition may be an alternative to other techniques of preservation. Aim of this study was to compare apparent total tract digestibility (D(t) ; barley, wheat, triticale, rye) of proximate nutrients and pre-caecal digestibility (D(pc); barley, wheat) of amino acids (AA), respectively, from cereal grains in ensiled and almost dry condition. Moistly harvested cereal grains (67-73% dry matter) were milled through a 4-mm sieve and ensiled with lactic acid bacteria (LAB, 3 × 10(5) colony forming units/g Lactobacillus plantarum DSMZ 8862 and 8866). To investigate D(t), two trials were conducted with six Mini-Lewe pigs and four German Landrace pigs, respectively. D(pc) of AA was determined using four German Landrace pigs with ileo-rectal anastomosis. D(t) of proximate nutrients did not differ between cereal grains and their silages, except for ether extract, which was more digestible in ensiled than dry wheat, triticale and rye (p < 0.05). Lysine content was lower in ensiled than dry barley and wheat. In barley, ensiling was accompanied by reduced D(pc) of lysine and histidine (p < 0.05). In wheat, ensiling increased D(pc) of lysine, methionine, threonine and leucin (p < 0.05). Ensiling of pre-mature cereal grains with LAB can serve as a reasonable storage alternative. However, as limited data are yet available, further research is required to understand completely the impact of ensiling on nutritional value as indicated, for example, by the lysine content and the D(pc) of certain AA. © 2010 Blackwell Verlag GmbH.

Top-down and bottom-up attention-to-memory: mapping functional connectivity in two distinct networks that underlie cued and uncued recognition memory.

PubMed

Burianová, Hana; Ciaramelli, Elisa; Grady, Cheryl L; Moscovitch, Morris

2012-11-15

The objective of this study was to examine the functional connectivity of brain regions active during cued and uncued recognition memory to test the idea that distinct networks would underlie these memory processes, as predicted by the attention-to-memory (AtoM) hypothesis. The AtoM hypothesis suggests that dorsal parietal cortex (DPC) allocates effortful top-down attention to memory retrieval during cued retrieval, whereas ventral parietal cortex (VPC) mediates spontaneous bottom-up capture of attention by memory during uncued retrieval. To identify networks associated with these two processes, we conducted a functional connectivity analysis of a left DPC and a left VPC region, both identified by a previous analysis of task-related regional activations. We hypothesized that the two parietal regions would be functionally connected with distinct neural networks, reflecting their engagement in the differential mnemonic processes. We found two spatially dissociated networks that overlapped only in the precuneus. During cued trials, DPC was functionally connected with dorsal attention areas, including the superior parietal lobules, right precuneus, and premotor cortex, as well as relevant memory areas, such as the left hippocampus and the middle frontal gyri. During uncued trials, VPC was functionally connected with ventral attention areas, including the supramarginal gyrus, cuneus, and right fusiform gyrus, as well as the parahippocampal gyrus. In addition, activity in the DPC network was associated with faster response times for cued retrieval. This is the first study to show a dissociation of the functional connectivity of posterior parietal regions during episodic memory retrieval, characterized by a top-down AtoM network involving DPC and a bottom-up AtoM network involving VPC. Copyright © 2012 Elsevier Inc. All rights reserved.

Surface-enhanced Raman scattering and DFT investigation of 1,5-diphenylcarbazide and its metal complexes with Ca(II), Mn(II), Fe(III) and Cu(II)

NASA Astrophysics Data System (ADS)

Szabó, László; Herman, Krisztian; Mircescu, Nicoleta Elena; Tódor, István Szabolcs; Simon, Botond Lorand; Boitor, Radu Alex; Leopold, Nicolae; Chiş, Vasile

2014-09-01

In recent years, surface-enhanced Raman scattering (SERS) has become an increasingly viable method for the detection of metal ions, evidenced by the existing studies on metal complexes. In this study, 1,5-diphenylcarbazide (DPC) and its Ca(II), Mn(II), Fe(III) and Cu(II) complexes were investigated by FTIR/ATR, FT-Raman and surface-enhanced Raman spectroscopies. The hybrid B3LYP exchange-correlation functional was used for the molecular geometry optimizations, molecular electrostatic potential (MEP) distribution and vibrational frequencies calculations of the DPC molecule and its complexes. Based on experimental and theoretical data, we were able to accurately identify unique and representative features for each DPC-metal complex, features that enable the detection of said metal complexes in millimolar concentrations.

Explicit Filtering Based Low-Dose Differential Phase Reconstruction Algorithm with the Grating Interferometry.

PubMed

Jiang, Xiaolei; Zhang, Li; Zhang, Ran; Yin, Hongxia; Wang, Zhenchang

2015-01-01

X-ray grating interferometry offers a novel framework for the study of weakly absorbing samples. Three kinds of information, that is, the attenuation, differential phase contrast (DPC), and dark-field images, can be obtained after a single scanning, providing additional and complementary information to the conventional attenuation image. Phase shifts of X-rays are measured by the DPC method; hence, DPC-CT reconstructs refraction indexes rather than attenuation coefficients. In this work, we propose an explicit filtering based low-dose differential phase reconstruction algorithm, which enables reconstruction from reduced scanning without artifacts. The algorithm adopts a differential algebraic reconstruction technique (DART) with the explicit filtering based sparse regularization rather than the commonly used total variation (TV) method. Both the numerical simulation and the biological sample experiment demonstrate the feasibility of the proposed algorithm.

Explicit Filtering Based Low-Dose Differential Phase Reconstruction Algorithm with the Grating Interferometry

PubMed Central

Zhang, Li; Zhang, Ran; Yin, Hongxia; Wang, Zhenchang

2015-01-01

X-ray grating interferometry offers a novel framework for the study of weakly absorbing samples. Three kinds of information, that is, the attenuation, differential phase contrast (DPC), and dark-field images, can be obtained after a single scanning, providing additional and complementary information to the conventional attenuation image. Phase shifts of X-rays are measured by the DPC method; hence, DPC-CT reconstructs refraction indexes rather than attenuation coefficients. In this work, we propose an explicit filtering based low-dose differential phase reconstruction algorithm, which enables reconstruction from reduced scanning without artifacts. The algorithm adopts a differential algebraic reconstruction technique (DART) with the explicit filtering based sparse regularization rather than the commonly used total variation (TV) method. Both the numerical simulation and the biological sample experiment demonstrate the feasibility of the proposed algorithm. PMID:26089971

An algebraic iterative reconstruction technique for differential X-ray phase-contrast computed tomography.

PubMed

Fu, Jian; Schleede, Simone; Tan, Renbo; Chen, Liyuan; Bech, Martin; Achterhold, Klaus; Gifford, Martin; Loewen, Rod; Ruth, Ronald; Pfeiffer, Franz

2013-09-01

Iterative reconstruction has a wide spectrum of proven advantages in the field of conventional X-ray absorption-based computed tomography (CT). In this paper, we report on an algebraic iterative reconstruction technique for grating-based differential phase-contrast CT (DPC-CT). Due to the differential nature of DPC-CT projections, a differential operator and a smoothing operator are added to the iterative reconstruction, compared to the one commonly used for absorption-based CT data. This work comprises a numerical study of the algorithm and its experimental verification using a dataset measured at a two-grating interferometer setup. Since the algorithm is easy to implement and allows for the extension to various regularization possibilities, we expect a significant impact of the method for improving future medical and industrial DPC-CT applications. Copyright © 2012. Published by Elsevier GmbH.

Up-regulation of genes in diphenylamine- and 1-methylcyclopropene-treated apples during cold storage

USDA-ARS?s Scientific Manuscript database

Cold storage reduces the rate of quality loss and extends availability of fresh apples in the marketplace, but several cultivars develop various postharvest browning disorders of the peel or flesh tissue such as superficial scald and external carbon dioxide injury. Postharvest 1-methylcyclopropene...

Radiative Decay Engineering 6: Fluorescence on One-Dimensional Photonic Crystals

PubMed Central

Badugu, Ramachandram; Nowaczyk, Kazimierz; Descrovi, Emiliano; Lakowicz, Joseph R.

2014-01-01

During the past decade the interactions of fluorophores with metallic particles and surfaces has become an active area of research. These near-field interactions of fluorophores with surface plasmons have resulted in increased brightness and directional emission. However, using metals provide some disadvantages, like quenching at short fluorophore-metal distances, increased rates of energy dissipation due to lossy metals. These unfavorable effects are not expected in dielectrics. In this paper we describe the interactions of fluorophores with one-dimensional (1D) photonic crystals (PCs), which have alternating layers of dielectrics with dimensions that create a photonic bandgap (PBG). Freely propagating light at the PBG wavelength will be reflected. However, similar with metals, we show that fluorophores within near-field distances of the 1DPC interacts with the structure. Our results demonstrated that these fluorophores can interact with both Internal Modes (IM) and Bloch Surface Waves (BSW) of the 1DPC. For fluorophores on the surface of the 1DPC the emission dominantly occurs through the 1DPC and into the substrate. We refer to these two phenomena together as Bragg Grating-Coupled Emission (BGCE). Here we describe our preliminary results on BGCE. 1DPCs are simple to fabricate and can be handled and reused without damage. We believe BGCE provide opportunities for new formats for fluorescence detection and sensing. PMID:23896462

Identifying Dynamic Protein Complexes Based on Gene Expression Profiles and PPI Networks

PubMed Central

Li, Min; Chen, Weijie; Wang, Jianxin; Pan, Yi

2014-01-01

Identification of protein complexes from protein-protein interaction networks has become a key problem for understanding cellular life in postgenomic era. Many computational methods have been proposed for identifying protein complexes. Up to now, the existing computational methods are mostly applied on static PPI networks. However, proteins and their interactions are dynamic in reality. Identifying dynamic protein complexes is more meaningful and challenging. In this paper, a novel algorithm, named DPC, is proposed to identify dynamic protein complexes by integrating PPI data and gene expression profiles. According to Core-Attachment assumption, these proteins which are always active in the molecular cycle are regarded as core proteins. The protein-complex cores are identified from these always active proteins by detecting dense subgraphs. Final protein complexes are extended from the protein-complex cores by adding attachments based on a topological character of “closeness” and dynamic meaning. The protein complexes produced by our algorithm DPC contain two parts: static core expressed in all the molecular cycle and dynamic attachments short-lived. The proposed algorithm DPC was applied on the data of Saccharomyces cerevisiae and the experimental results show that DPC outperforms CMC, MCL, SPICi, HC-PIN, COACH, and Core-Attachment based on the validation of matching with known complexes and hF-measures. PMID:24963481

Efficiency of inpatient orthopedic surgery in Japan: a medical claims database analysis.

PubMed

Nakata, Yoshinori; Yoshimura, Tatsuya; Watanabe, Yuichi; Otake, Hiroshi; Oiso, Giichiro; Sawa, Tomohiro

2017-07-10

Purpose The purpose of this paper is to determine the characteristics of healthcare facilities that produce the most efficient inpatient orthopedic surgery using a large-scale medical claims database in Japan. Design/methodology/approach Reimbursement claims data were obtained from April 1 through September 30, 2014. Input-oriented Banker-Charnes-Cooper model of data envelopment analysis (DEA) was employed. The decision-making unit was defined as a healthcare facility where orthopedic surgery was performed. Inputs were defined as the length of stay, the number of beds, and the total costs of expensive surgical devices. Output was defined as total surgical fees for each surgery. Efficiency scores of healthcare facilities were compared among different categories of healthcare facilities. Findings The efficiency scores of healthcare facilities with a diagnosis-procedure combination (DPC) reimbursement were significantly lower than those without DPC ( p=0.0000). All the efficiency scores of clinics with beds were 1. Their efficiency scores were significantly higher than those of university hospitals, public hospitals, and other hospitals ( p=0.0000). Originality/value This is the first research that applied DEA for orthopedic surgery in Japan. The healthcare facilities with DPC reimbursement were less efficient than those without DPC. The clinics with beds were the most efficient among all types of management bodies of healthcare facilities.

Host Specific Diversity in Lactobacillus johnsonii as Evidenced by a Major Chromosomal Inversion and Phage Resistance Mechanisms

PubMed Central

Guinane, Caitriona M.; Kent, Robert M.; Norberg, Sarah; Hill, Colin; Fitzgerald, Gerald F.; Stanton, Catherine; Ross, R. Paul

2011-01-01

Genetic diversity and genomic rearrangements are a driving force in bacterial evolution and niche adaptation. We sequenced and annotated the genome of Lactobacillus johnsonii DPC6026, a strain isolated from the porcine intestinal tract. Although the genome of DPC6026 is similar in size (1.97mbp) and GC content (34.8%) to the sequenced human isolate L. johnsonii NCC 533, a large symmetrical inversion of approximately 750 kb differentiated the two strains. Comparative analysis among 12 other strains of L. johnsonii including 8 porcine, 3 human and 1 poultry isolate indicated that the genome architecture found in DPC6026 is more common within the species than that of NCC 533. Furthermore a number of unique features were annotated in DPC6026, some of which are likely to have been acquired by horizontal gene transfer (HGT) and contribute to protection against phage infection. A putative type III restriction-modification system was identified, as were novel Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) elements. Interestingly, these particular elements are not widely distributed among L. johnsonii strains. Taken together these data suggest intra-species genomic rearrangements and significant genetic diversity within the L. johnsonii species and indicate towards a host-specific divergence of L. johnsonii strains with respect to genome inversion and phage exposure. PMID:21533100

Host specific diversity in Lactobacillus johnsonii as evidenced by a major chromosomal inversion and phage resistance mechanisms.

PubMed

Guinane, Caitriona M; Kent, Robert M; Norberg, Sarah; Hill, Colin; Fitzgerald, Gerald F; Stanton, Catherine; Ross, R Paul

2011-04-20

Genetic diversity and genomic rearrangements are a driving force in bacterial evolution and niche adaptation. We sequenced and annotated the genome of Lactobacillus johnsonii DPC6026, a strain isolated from the porcine intestinal tract. Although the genome of DPC6026 is similar in size (1.97 mbp) and GC content (34.8%) to the sequenced human isolate L. johnsonii NCC 533, a large symmetrical inversion of approximately 750 kb differentiated the two strains. Comparative analysis among 12 other strains of L. johnsonii including 8 porcine, 3 human and 1 poultry isolate indicated that the genome architecture found in DPC6026 is more common within the species than that of NCC 533. Furthermore a number of unique features were annotated in DPC6026, some of which are likely to have been acquired by horizontal gene transfer (HGT) and contribute to protection against phage infection. A putative type III restriction-modification system was identified, as were novel Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) elements. Interestingly, these particular elements are not widely distributed among L. johnsonii strains. Taken together these data suggest intra-species genomic rearrangements and significant genetic diversity within the L. johnsonii species and indicate towards a host-specific divergence of L. johnsonii strains with respect to genome inversion and phage exposure.

Grating-based phase contrast tomosynthesis imaging: Proof-of-concept experimental studies

PubMed Central

Li, Ke; Ge, Yongshuai; Garrett, John; Bevins, Nicholas; Zambelli, Joseph; Chen, Guang-Hong

2014-01-01

Purpose: This paper concerns the feasibility of x-ray differential phase contrast (DPC) tomosynthesis imaging using a grating-based DPC benchtop experimental system, which is equipped with a commercial digital flat-panel detector and a medical-grade rotating-anode x-ray tube. An extensive system characterization was performed to quantify its imaging performance. Methods: The major components of the benchtop system include a diagnostic x-ray tube with a 1.0 mm nominal focal spot size, a flat-panel detector with 96 μm pixel pitch, a sample stage that rotates within a limited angular span of ±30°, and a Talbot-Lau interferometer with three x-ray gratings. A total of 21 projection views acquired with 3° increments were used to reconstruct three sets of tomosynthetic image volumes, including the conventional absorption contrast tomosynthesis image volume (AC-tomo) reconstructed using the filtered-backprojection (FBP) algorithm with the ramp kernel, the phase contrast tomosynthesis image volume (PC-tomo) reconstructed using FBP with a Hilbert kernel, and the differential phase contrast tomosynthesis image volume (DPC-tomo) reconstructed using the shift-and-add algorithm. Three inhouse physical phantoms containing tissue-surrogate materials were used to characterize the signal linearity, the signal difference-to-noise ratio (SDNR), the three-dimensional noise power spectrum (3D NPS), and the through-plane artifact spread function (ASF). Results: While DPC-tomo highlights edges and interfaces in the image object, PC-tomo removes the differential nature of the DPC projection data and its pixel values are linearly related to the decrement of the real part of the x-ray refractive index. The SDNR values of polyoxymethylene in water and polystyrene in oil are 1.5 and 1.0, respectively, in AC-tomo, and the values were improved to 3.0 and 2.0, respectively, in PC-tomo. PC-tomo and AC-tomo demonstrate equivalent ASF, but their noise characteristics quantified by the 3D NPS were found to be different due to the difference in the tomosynthesis image reconstruction algorithms. Conclusions: It is feasible to simultaneously generate x-ray differential phase contrast, phase contrast, and absorption contrast tomosynthesis images using a grating-based data acquisition setup. The method shows promise in improving the visibility of several low-density materials and therefore merits further investigation. PMID:24387511

ISCCP-D2like-GEO Ed3A

Atmospheric Science Data Center

2018-05-16

ISCCP-D2like-GEO Ed3A Project Title:  CERES Discipline:  ... Order Data Guide Documents:  GEO Description/Abstract Detailed CERES ISCCP-D2like Product ... Data Products Catalog:  DPC_ISCCP-D2like-GEO_R5V3  (PDF) Readme Files:  Readme GEO R5-987 ...

Nano-hydroxyapatite and calcium-enriched mixture for pulp capping of sound primary teeth: a randomized clinical trial.

PubMed

Haghgoo, Roza; Asgary, Saeed; Mashhadi Abbas, Fatemeh; Montazeri Hedeshi, Roshanak

2015-01-01

Nano-hydroxyapatite (NHA) has been used for regeneration of osseous defects. Calcium-enriched mixture (CEM) cement is also used for various dental treatments. This trial compared the efficacy of NHA and CEM cement for direct pulp capping (DPC) of sound primary teeth. In this randomized clinical trial with split-mouth design, after attaining informed consent, 20 sound primary canines scheduled for orthodontic extraction, were selected. After mechanical pulp exposure, the exposed site was capped with either NHA or CEM cement and then immediately restored with glass-ionomer and resin composite. The teeth were extracted after two months and examined histologically. Parameters of hard tissue bridge (HTB) formation, its type and quality as well as pulpal inflammation scores were compared between the two experimental groups. The data were analyzed using the Mann Whitney U and Fisher's exact test. The level of significance was set at 0.001. All CEM specimens showed inflammation score of 0 (less than 10%). However, in NHA group, inflammation scores of 0 (less than 10%), 1 (10%-30%) and 2 (30%-50%) were observed in 2 (20%), 4 (40%) and 4 (40%) specimens, respectively (P<0.001). HTB was formed in all CEM specimens while it was developed in 2 specimens of NHA (20%; P<0.001). All CEM specimens showed normal pulp; only two cases in NHA group (20%) demonstrated uninflamed normal pulp. CEM cement was superior to NHA as a DPC agent in terms of HTB formation and pulp inflammation scores. It is a suitable material for the DPC of primary teeth.

Microwave assisted transformation of N,N-diphenylamine as precursors of organic light emitting diodes (OLED)

NASA Astrophysics Data System (ADS)

Jefri, Wahyuningrum, Deana

2015-09-01

In this research, study on the transformation of N,N-diphenylamine (DPA) using iodine (I2) utilizing solid state Microwave Assisted Organic Synthesis (MAOS) method has been carried out. The reaction was performed by variations of three parameters namely the mole of reagents, the amount and type of solid support (alumina/Al2O3), and the reaction conditions. Experimental results showed that neutral-alumina was a better solid support than basic-alumina. The optimum temperature for the reaction was approximately at 125-133 °C with reaction time of 15 minutes and microwave reactor power at 500-600 W. The separation of the yellowish green product solution with preparative Thin Layer Chromatography (TLC) method using n-hexane:ethyl acetate = 4:1 (v/v) as eluent yielded two fractions (I and II) and both fractions can undergo fluorescence under 365 nm UV light. Based on the LC chromatogram with methanol:water = 95:5 (v/v) as eluent and its corresponding mass spectra (ESI+), fraction I contained three compounds, which were tetracarbazole A, triphenylamine, and impurities in the form of plasticizer such as bis(2-ethylhexyl) phthalate. Fraction II also contained three compounds, which were tetracarbazole C, tetraphenylhydrazine, and plasticizer such as bis(2-ethylhexyl) phthalate. Both FT-IR (KBr disks) and NMR (500 MHz, CDCl3) spectra of fraction I and II confirmed the aromatic amine groups in those compounds. The observed fluorescence colors of fraction I and II were violet and violet-blue, respectively. Based on their structures and fluorescence characters, the compounds in fraction I and II have the potential to be used as Organic Light Emitting Diode (OLED) compound precursors.

Microwave assisted transformation of N,N-diphenylamine as precursors of organic light emitting diodes (OLED)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jefri,; Wahyuningrum, Deana, E-mail: deana@chem.itb.ac.id

2015-09-30

In this research, study on the transformation of N,N-diphenylamine (DPA) using iodine (I2) utilizing solid state Microwave Assisted Organic Synthesis (MAOS) method has been carried out. The reaction was performed by variations of three parameters namely the mole of reagents, the amount and type of solid support (alumina/Al2O3), and the reaction conditions. Experimental results showed that neutral-alumina was a better solid support than basic-alumina. The optimum temperature for the reaction was approximately at 125-133 °C with reaction time of 15 minutes and microwave reactor power at 500-600 W. The separation of the yellowish green product solution with preparative Thin Layer Chromatographymore » (TLC) method using n-hexane:ethyl acetate = 4:1 (v/v) as eluent yielded two fractions (I and II) and both fractions can undergo fluorescence under 365 nm UV light. Based on the LC chromatogram with methanol:water = 95:5 (v/v) as eluent and its corresponding mass spectra (ESI+), fraction I contained three compounds, which were tetracarbazole A, triphenylamine, and impurities in the form of plasticizer such as bis(2-ethylhexyl) phthalate. Fraction II also contained three compounds, which were tetracarbazole C, tetraphenylhydrazine, and plasticizer such as bis(2-ethylhexyl) phthalate. Both FT-IR (KBr disks) and NMR (500 MHz, CDCl{sub 3}) spectra of fraction I and II confirmed the aromatic amine groups in those compounds. The observed fluorescence colors of fraction I and II were violet and violet-blue, respectively. Based on their structures and fluorescence characters, the compounds in fraction I and II have the potential to be used as Organic Light Emitting Diode (OLED) compound precursors.« less

Highly Sensitive Determination of the Polaron-Induced Optical Absorption of Organic Charge-Transport Materials

NASA Astrophysics Data System (ADS)

Rabe, T.; Görrn, P.; Lehnhardt, M.; Tilgner, M.; Riedl, T.; Kowalsky, W.

2009-04-01

We examine polaron-induced absorption in organic transport materials using a highly sensitive measurement technique. A hole only device is embedded into a low-loss TE2 waveguide structure, and the current induced change of the waveguide absorption is measured. The exemplary study of 2,2',7,7'-tetrakis(N,N-diphenylamine)-9,9'-spiro-bifluorene (S-TAD) reveals a very low polaron absorption cross section of σp≤2.6×10-18cm2 for 560 nm ≤λ≤660nm. The accuracy of this data is unsurpassed by other techniques used for the unambiguous study of polaronic species in organic thin films.

The phosphatidyl choline exchange properties in the cytosol of Aspergillus niger.

PubMed

Audigier-Petit, C; Letoublon, R; Fayet, Y; Got, R; Frot-Coutaz, J

1986-01-01

The presence of a PC-binding activity in the cytosol of Aspergillus niger van Tieghem has been established by measuring the reversible exchange of labeled DPC between an adsorbent (celite) and the cytosol. We have shown that this exchange is dependent upon the temperature and the ionic strength and it varies linearly with the protein concentration. This PC-binding activity is able to discriminate between DPC and some other phospholipids.

[Utilization of Big Data in Medicine and Future Outlook].

PubMed

Kinosada, Yasutomi; Uematsu, Machiko; Fujiwara, Takuya

2016-03-01

"Big data" is a new buzzword. The point is not to be dazzled by the volume of data, but rather to analyze it, and convert it into insights, innovations, and business value. There are also real differences between conventional analytics and big data. In this article, we show some results of big data analysis using open DPC (Diagnosis Procedure Combination) data in areas of the central part of JAPAN: Toyama, Ishikawa, Fukui, Nagano, Gifu, Aichi, Shizuoka, and Mie Prefectures. These 8 prefectures contain 51 medical administration areas called the second medical area. By applying big data analysis techniques such as k-means, hierarchical clustering, and self-organizing maps to DPC data, we can visualize the disease structure and detect similarities or variations among the 51 second medical areas. The combination of a big data analysis technique and open DPC data is a very powerful method to depict real figures on patient distribution in Japan.

Perfusion of isolated carotid sinus with hydrogen sulfide attenuated the renal sympathetic nerve activity in anesthetized male rats.

PubMed

Guo, Q; Wu, Y; Xue, H; Xiao, L; Jin, S; Wang, R

2016-07-18

The purpose of the present study was to define the indirect central effect of hydrogen sulfide (H(2)S) on baroreflex control of sympathetic outflow. Perfusing the isolated carotid sinus with sodium hydrosulfide (NaHS), a H(2)S donor, the effect of H(2)S was measured by recording changes of renal sympathetic nerve activity (RSNA) in anesthetized male rats. Perfusion of isolated carotid sinus with NaHS (25, 50, 100 micromol/l) dose and time-dependently inhibited sympathetic outflow. Preconditioning of glibenclamide (20 micromol/l), a ATP-sensitive K(+) channels (K(ATP)) blocker, the above effect of NaHS was removed. With 1, 4-dihydro-2, 6-dimethyl-5-nitro-4-(2-[trifluoromethyl] phenyl) pyridine-3-carboxylic acid methyl ester (Bay K8644, 500 nmol/l) pretreatment, which is an agonist of L-calcium channels, the effect of NaHS was eliminated. Perfusion of cystathionine gamma-lyase (CSE) inhibitor, DL-propargylglycine (PPG, 200 micromol/l), increased sympathetic outflow. The results show that exogenous H(2)S in the carotid sinus inhibits sympathetic outflow. The effect of H(2)S is attributed to opening K(ATP) channels and closing the L-calcium channels.

Integrated metabolomic and transcriptomic profiling illustrates successive phases of increasing gene expression associated with chilling-related apple peel cell death

USDA-ARS?s Scientific Manuscript database

Superficial scald is a chilling-related storage disorder of apple caused by the death of peel epidermal and hypodermal cells and associated discoloration. It is controlled using postharvest antioxidant (diphenylamine; DPA) and ethylene action inhibitor (1-methylcyclopropene; 1-MCP), and/or controlle...

Towards optimization of an organotypic assay system that imitates human hair follicle-like epithelial-mesenchymal interactions.

PubMed

Havlickova, B; Bíró, T; Mescalchin, A; Arenberger, P; Paus, R

2004-10-01

Human hair growth can currently be studied in vitro by the use of organ-cultured scalp hair follicles (HFs). However, simplified organotypic systems are needed for dissecting the underlying epithelial-mesenchymal interactions and as screening tools for candidate hair growth-modulatory agents. To optimize the design and culture conditions of previously published organotypic systems that imitate epithelial-mesenchymal interactions in the human HF as closely as possible. Continuous submerged organotypic 'sandwich' cultures were established. These consist of a pseudodermis (collagen I mixed with and contracted by human interfollicular dermal fibroblasts) on which one of two upper layers is placed: either a mixture of Matrigel basement membrane matrix (BD Biosciences, Bedford, MA, U.S.A.) and follicular dermal papilla fibroblasts (DPC), with outer root sheath keratinocytes (ORSK) layered on the top ('layered' system), or a mixture of Matrigel, DPC and ORSK ('mixed' system). Morphological and functional characteristics of these 'folliculoid sandwiches' were then assessed by routine histology, histomorphometry and immunohistochemistry. In both 'layered' and 'mixed' systems, the ORSK formed spheroid epithelial cell aggregates, which retained their characteristic keratin expression pattern (i.e. cytokeratin 6). In the 'mixed' sandwich model the size of the epithelial cell aggregates was smaller, but the numbers of ORSK were significantly higher than in the 'layered' model at day 14 in the culture. ORSK proliferated better in the 'mixed' than in the 'layered' sandwich system, regardless of the calcium or serum content of the media, whereas apoptosis of ORSK was lowest in the 'mixed' system in serum-free, low calcium medium. The kinetics of proliferation and apoptosis of DPC, which retained their characteristic expression of versican, were similar in both systems. However, proliferation and apoptosis of DPC were higher in the presence of serum and/or under high calcium conditions. Our results underscore the importance of structural design and medium composition for epithelial-mesenchymal interactions as they occur in the human HF. Specifically, we report a new organotypic submerged 'folliculoid sandwich' system with serum-free, low calcium medium and a mixture of interacting human DPC and ORSK, which offers several advantages over previously available assays. This system allows the standardized assessment of the effects of a test agent on the proliferation, apoptosis and key marker expression of human ORSK and DPC under substantially simplified in vitro conditions which approximate the in vivo situation.

Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure.

PubMed

Zugck, Christian; Haunstetter, Armin; Krüger, Carsten; Kell, Robert; Schellberg, Dieter; Kübler, Wolfgang; Haass, Markus

2002-05-15

This prospective study tested the impact of beta-blocker treatment on currently used risk predictors in congestive heart failure (CHF). Given the survival benefit obtained by beta-blockade, risk stratification by factors established in the "pre-beta-blocker era" may be questioned. The study included 408 patients who had CHF with left ventricular ejection fraction (LVEF) <45%, all treated with an angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist, who were classified into those receiving a beta-blocker (n = 165) and those who were not (n = 243). In all patients, LVEF, peak oxygen consumption (peakVO(2)), plasma norepinephrine (NE) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined. Although the New York Heart Association functional class (2.2 +/- 0.7 vs. 2.3 +/- 0.7), peakVO(2) (14.4 +/- 5.2 ml/min per kg vs. 14.4 +/- 5.5 ml/min per kg) and NT-proBNP (337 +/- 360 pmol/l vs. 434 +/- 538 pmol/l) were similar in the groups with and without beta-blocker treatment, the group with beta-blocker treatment had a lower heart rate (68 +/- 30 beats/min vs. 76 +/- 30 beats/min), lower NE (1.7 +/- 1.2 nmol/l vs. 2.5 +/- 2.2 nmol/l) and higher LVEF (24 +/- 10% vs. 21 +/- 9%; all p < 0.05). Within one year, 34% of patients without beta-blocker treatment, but only 16% of those with beta-blocker treatment (p < 0.001), reached the combined end point, defined as hospital admission due to worsening CHF and/or cardiac death. A beneficial effect of beta-blocker treatment was most obvious in the advanced stages of CHF, because the end-point rates were markedly lower (all p < 0.05) in the group with beta-blocker treatment versus the group without it, as characterized by peakVO(2) <10 ml/min per kg (26% vs. 64%), LVEF < or = 20% (25% vs. 45%), NE >2.24 nmol/l (18% vs. 40%) and NT-proBNP >364 pmol/l (27% vs. 45%), although patients with beta-blocker treatment received only 37 +/- 21% of the maximal recommended beta-blocker dosages. The prognostic value of variables used for risk stratification of patients with CHF is markedly influenced by beta-blocker treatment. Therefore, in the beta-blocker era, a re-evaluation of the selection criteria for heart transplantation is warranted.

Acid stress management by Cronobacter sakazakii.

PubMed

Alvarez-Ordóñez, Avelino; Cummins, Conor; Deasy, Thérèse; Clifford, Tanya; Begley, Máire; Hill, Colin

2014-05-16

Cronobacter sakazakii is a foodborne pathogenic microorganism associated with sporadic cases of neonatal meningitis, necrotising enterocolitis, septicaemia, bloody diarrhoea and brain abscesses acquired through the consumption of contaminated powdered infant formula (PIF). This study aimed to investigate the growth of C. sakazakii DPC6529, a particularly stress tolerant clinical isolate, in acidified laboratory media and PIF. The possibility of a stationary-phase acid tolerance response (ATR) was also investigated. C. sakazakii DPC6529 grew in LB broth acidified to pH4.2 with hydrochloric acid (HCl) and was capable of relatively fast growth in PIF acidified to pH5.0 with HCl, representing the stomach pH reported for newborns and infants. Moreover, bacterial growth in LB broth supplemented with 1% (w/v) glucose gave rise to a stationary-phase ATR which resulted in enhanced survival against a subsequent acid challenge at pH3.0. A transposon mutagenesis approach was used to shed light on some of the molecular mechanisms involved in the response C. sakazakii DPC6529 to normally lethal acid exposures. The data suggests that repairing damage in proteins and nucleic acids, posttranscriptional modification of tRNA molecules and maintenance of the integrity of the cellular envelope are key processes in the defence against acid stress. Clones carrying transposon insertions in genes encoding the envelope stress response regulators CpxR and OmpR were identified as acid-sensitive mutants. Further analyses of the ompR defective mutant and its complemented counterpart evidenced that OmpR is a key player in the response of C. sakazakii to acid stress, although it was not essential to mount an active stationary-phase ATR, at least under the tested conditions. The ability of C. sakazakii DPC6529 to grow in acid environments and to develop an adaptive stationary-phase ATR may allow for its survival or even proliferation within the infant gastrointestinal tract after consumption of contaminated milk formulae. Copyright © 2014 Elsevier B.V. All rights reserved.

Talbot phase-contrast X-ray imaging for the small joints of the hand

PubMed Central

Stutman, Dan; Beck, Thomas J; Carrino, John A; Bingham, Clifton O

2011-01-01

A high resolution radiographic method for soft tissues in the small joints of the hand would aid in the study and treatment of Rheumatoid Arthritis (RA) and Osteoarthritis (OA), which often attacks these joints. Of particular interest would be imaging with <100 μm resolution the joint cartilage, whose integrity is a main indicator of disease. Differential phase-contrast or refraction based X-ray imaging (DPC) with Talbot grating interferometers could provide such a method, since it enhances soft tissue contrast and it can be implemented with conventional X-ray tubes. A numerical joint phantom was first developed to assess the angular sensitivity and spectrum needed for a hand DPC system. The model predicts that due to quite similar refraction indexes for joint soft tissues, the refraction effects are very small, requiring high angular resolution. To compare our model to experiment we built a high resolution bench-top interferometer using 10 μm period gratings, a W anode tube and a CCD based detector. Imaging experiments on animal cartilage and on a human finger support the model predictions. For instance, the estimated difference between the index of refraction of cartilage and water is of only several percent at ~25 keV mean energy, comparable to that between the linear attenuation coefficients. The potential advantage of DPC imaging comes thus mainly from the edge enhancement at the soft tissue interfaces. Experiments using a cadaveric human finger are also qualitatively consistent with the joint model, showing that refraction contrast is dominated by tendon embedded in muscle, with the cartilage layer difficult to observe in our conditions. Nevertheless, the model predicts that a DPC radiographic system for the small hand joints of the hand could be feasible using a low energy quasi-monochromatic source, such as a K-edge filtered Rh or Mo tube, in conjunction with a ~2 m long ‘symmetric’ interferometer operated in a high Talbot order. PMID:21841214

Talbot phase-contrast x-ray imaging for the small joints of the hand

NASA Astrophysics Data System (ADS)

Stutman, Dan; Beck, Thomas J.; Carrino, John A.; Bingham, Clifton O.

2011-09-01

A high-resolution radiographic method for soft tissues in the small joints of the hand would aid in the study and treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), which often attacks these joints. Of particular interest would be imaging with <100 µm resolution the joint cartilage, whose integrity is a main indicator of disease. Differential phase-contrast (DPC) or refraction-based x-ray imaging with Talbot grating interferometers could provide such a method, since it enhances soft tissue contrast and can be implemented with conventional x-ray tubes. A numerical joint phantom was first developed to assess the angular sensitivity and spectrum needed for a hand DPC system. The model predicts that, due to quite similar refraction indexes for joint soft tissues, the refraction effects are very small, requiring high angular resolution. To compare our model to experiment we built a high-resolution bench-top interferometer using 10 µm period gratings, a W anode tube and a CCD-based detector. Imaging experiments on animal cartilage and on a human finger support the model predictions. For instance, the estimated difference between the index of refraction of cartilage and water is of only several percent at ~25 keV mean energy, comparable to that between the linear attenuation coefficients. The potential advantage of DPC imaging thus comes mainly from the edge enhancement at the soft tissue interfaces. Experiments using a cadaveric human finger are also qualitatively consistent with the joint model, showing that refraction contrast is dominated by tendon embedded in muscle, with the cartilage layer difficult to observe in our conditions. Nevertheless, the model predicts that a DPC radiographic system for the small hand joints of the hand could be feasible using a low energy quasi-monochromatic source, such as a K-edge filtered Rh or Mo tube, in conjunction with a ~2 m long 'symmetric' interferometer operated in a high Talbot order.

Lactoferrin affects the adherence and invasion of Streptococcus dysgalactiae ssp. dysgalactiae in mammary epithelial cells.

PubMed

O'Halloran, Fiona; Beecher, Christine; Chaurin, Valerie; Sweeney, Torres; Giblin, Linda

2016-06-01

Streptococcus dysgalactiae ssp. dysgalactiae is an important causative agent of bovine mastitis worldwide. Lactoferrin is an innate immune protein that is associated with many functions including immunomodulatory, antiproliferative, and antimicrobial properties. This study aimed to investigate the interactions between lactoferrin and a clinical bovine mastitis isolate, Strep. dysgalactiae ssp. dysgalactiae DPC5345. Initially a deliberate in vivo bovine intramammary challenge was performed with Strep. dysgalactiae DPC5345. Results demonstrated a significant difference in lactoferrin mRNA levels in milk cells between the control and infused quarters 7h postinfusion. Milk lactoferrin levels in the Strep. dysgalactiae DPC5345 infused quarters were significantly increased compared with control quarters at 48h postinfusion. In vitro studies demonstrated that lactoferrin had a bacteriostatic effect on the growth of Strep. dysgalactiae DPC5345 and significantly decreased the ability of the bacteria to internalize into HC-11 mammary epithelial cells. Confocal microscopy images of HC-11 cells exposed to Strep. dysgalactiae and lactoferrin further supported this effect by demonstrating reduced invasion of bacteria to HC-11 cells. The combined data suggest that a bovine immune response to Strep. dysgalactiae infection includes a significant increase in lactoferrin expression in vivo, and based on in vitro data, lactoferrin limits mammary cell invasion of this pathogen by binding to the bacteria and preventing its adherence. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Examination of the Difference in Medical Treatment Contents According to Major Diagnostic Category of Hospital Group I and Group II Using the Diagnosis Procedure Combination Survey Data].

PubMed

Nakajima, Hisato; Yano, Kouya; Nagasawa, Kaoko; Kobayashi, Eiji; Yokota, Kuninobu

2015-01-01

A difference in the medical treatment situation between the first group and the second group of the hospital group in the DPC system was clarified using Diagnosis Procedure Combination (DPC) survey data according to Major Diagnostic Category (MDC). Furthermore, the division between the first group and the second group was examined. DPC survey data collected in 2012 was used. According to MDC, significant differences in the patient ratio of hospitalization, the number of planned hospitalizations, the number of emergency hospitalizations, the number of ambulance conveyances, and the number of treatments were considered. Then, by the Mahalanobis-Taguchi method, distributions of the Mahalanobis distance and item choice according to MDC were considered. Many items according to MDC showed significant differences between the first group and the second group. The Mahalanobis distance was increased by MDC 16 disease when divided by the Mahalanobis distance of 1.0 between the first group and the second group. The item, which contributed to the calculation of the Mahalanobis distance by item choice, varied and showed a difference between the first group and the second group. The second group was authorized by the hospital followed by the first group. However, the results showed significant differences in the number of DPC survey data and the Mahalanobis distance of many items.

Chromium(VI) release from leather and metals can be detected with a diphenylcarbazide spot test.

PubMed

Bregnbak, David; Johansen, Jeanne D; Jellesen, Morten S; Zachariae, Claus; Thyssen, Jacob P

2015-11-01

Along with chromium, nickel and cobalt are the clinically most important metal allergens. However, unlike for nickel and cobalt, there is no validated colorimetric spot test that detects chromium. Such a test could help both clinicians and their patients with chromium dermatitis to identify culprit exposures. To evaluate the use of diphenylcarbazide (DPC) as a spot test reagent for the identification of chromium(VI) release. A colorimetric chromium(VI) spot test based on DPC was prepared and used on different items from small market surveys. The DPC spot test was able to identify chromium(VI) release at 0.5 ppm without interference from other pure metals, alloys, or leather. A market survey using the test showed no chromium(VI) release from work tools (0/100). However, chromium(VI) release from metal screws (7/60), one earring (1/50), leather shoes (4/100) and leather gloves (6/11) was observed. We found no false-positive test reactions. Confirmatory testing was performed with X-ray fluorescence (XRF) and spectrophotometrically on extraction fluids. The use of DPC as a colorimetric spot test reagent appears to be a good and valid test method for detecting the release of chromium(VI) ions from leather and metal articles. The spot test has the potential to become a valuable screening tool. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of DNA–protein crosslinks (DPCs) by novel direct fluorescence labeling methods: distinct stabilities of aldehyde and radiation-induced DPCs

PubMed Central

Shoulkamy, Mahmoud I.; Nakano, Toshiaki; Ohshima, Makiko; Hirayama, Ryoichi; Uzawa, Akiko; Furusawa, Yoshiya; Ide, Hiroshi

2012-01-01

Proteins are covalently trapped on DNA to form DNA–protein crosslinks (DPCs) when cells are exposed to DNA-damaging agents. DPCs interfere with many aspects of DNA transactions. The current DPC detection methods indirectly measure crosslinked proteins (CLPs) through DNA tethered to proteins. However, a major drawback of such methods is the non-linear relationship between the amounts of DNA and CLPs, which makes quantitative data interpretation difficult. Here we developed novel methods of DPC detection based on direct CLP measurement, whereby CLPs in DNA isolated from cells are labeled with fluorescein isothiocyanate (FITC) and quantified by fluorometry or western blotting using anti-FITC antibodies. Both formats successfully monitored the induction and elimination of DPCs in cultured cells exposed to aldehydes and mouse tumors exposed to ionizing radiation (carbon-ion beams). The fluorometric and western blotting formats require 30 and 0.3 μg of DNA, respectively. Analyses of the isolated genomic DPCs revealed that both aldehydes and ionizing radiation produce two types of DPC with distinct stabilities. The stable components of aldehyde-induced DPCs have half-lives of up to days. Interestingly, that of radiation-induced DPCs has an infinite half-life, suggesting that the stable DPC component exerts a profound effect on DNA transactions over many cell cycles. PMID:22730301

Study on the DNA-protein crosslinks induced by chromium (VI) in SPC-A1

NASA Astrophysics Data System (ADS)

Liu, Yanqun; Ding, Jianjun; Lu, Xiongbing; You, Hao

2018-01-01

Objective: This study was designed to investigate the effect of chromium (VI) on DNA-protein crosslinks (DPC) of SPC-A1 cells. Methods: We exposed SPC-A1 cells were cultured in 1640 medium and treated with the SPC-A1 cells in vitro to different concentrations of Hexavalent chromium Cr(VI) for 2h, the KC1-SDS precipitation assay were used to measure the DNA-protein cross-linking effect. Results: All the different concentrations of Cr(VI) could cause the increase of DPC coefficient in SPC-A1 cells. But this effect was not significant (P>0.05) at low concentrations; while in high concentration Cr(VI) induced SPC-A1 cells could produce DNA-protein cross-linking effect significantly (P<0.05). Conclusions: chromium (VI) could induce DNA-protein crosslink.

Progesterone is critical for the development of mouse embryos.

PubMed

Zhang, Cong; Murphy, Bruce D

2014-08-01

Infertility affects approximately 10-15 % of reproductive-aged couples, and embryo loss due to preimplantation death is common to many mammals. Previous studies showed that a complex series of interactive molecular events are associated with this process, especially hormones (progesterone and estrogens) and growth factors, and are important for the cleavage and differentiation of the blastocysts. Yet, the mechanism of preimplantation embryo development is unclear. Using conditional knockout mice (CKO), we showed the development of blastocyst is tightly controlled by the level of progesterone (P4); furthermore, we found that the time when P4 should increase is also crucial for the formation of blastocysts. In CKO mice whose Lrh1 (liver receptor homolog 1) is deleted under the expression of Cre recombinase driven by progesterone receptor promoter, which reduced P4 synthesis, few of their embryos can reach blastocyst stage. When these CKO mice were supplied with P4 in the afternoon of dpc 1 (day post copulation), most of the embryos can form blastocysts; when CKO mice were supplied with P4 from the morning of dpc1, one-third of the embryos can reach blastocyst stage; however, the supplement of P4 in the morning of dpc 2 made very few of the embryos become blastocysts. We conclude that early exposure to P4 is essential for timely progression of early embryogenesis in the mouse.

Proliferating Cell Nuclear Antigen (PCNA) Regulates Primordial Follicle Assembly by Promoting Apoptosis of Oocytes in Fetal and Neonatal Mouse Ovaries

PubMed Central

Zhang, Yuanwei; Jiang, Xiaohua; Zhang, Huan; Ma, Tieliang; Zheng, Wei; Sun, Rui; Shen, Wei; Sha, Jiahao; Cooke, Howard J.; Shi, Qinghua

2011-01-01

Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA), a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer guanulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries. PMID:21253613

Casein Fermentate of Lactobacillus animalis DPC6134 Contains a Range of Novel Propeptide Angiotensin-Converting Enzyme Inhibitors▿

PubMed Central

Hayes, M.; Stanton, C.; Slattery, H.; O'Sullivan, O.; Hill, C.; Fitzgerald, G. F.; Ross, R. P.

2007-01-01

This work evaluated the angiotensin-converting-enzyme (ACE)-inhibitory activities of a bovine sodium caseinate fermentate generated using the proteolytic capabilities of the porcine small intestinal isolate Lactobacillus animalis DPC6134 (NCIMB deposit 41355). The crude 10-kDa L. animalis DPC6134 fermentate exhibited ACE-inhibitory activity of 85.51% (±15%) and had a 50% inhibitory concentration (IC50) of 0.8 mg protein/ml compared to captopril, which had an IC50 value of 0.005 mg/ml. Fractionation of the crude L. animalis DPC6134 fermentate by membrane filtration and reversed-phase high-performance liquid chromatography (HPLC) generated three bioactive fractions from a total of 72 fractions. Fractions 10, 19, and 43 displayed ACE-inhibitory activity percentages of 67.53 (±15), 83.71 (±19), and 42.36 (±11), respectively, where ACE inhibition was determined with 80 μl of the fractions with protein concentrations of 0.5 mg/ml. HPLC and mass spectrometry analysis identified 25 distinct peptide sequences derived from α-, β-, and κ-caseins. In silico predictions, based on the C-terminal tetrapeptide sequences, suggested that peptide NIPPLTQTPVVVPPFIQ, corresponding to β-casein f(73-89); peptide IGSENSEKTTMP, corresponding to αs1-casein f(201212); peptide SQSKVLPVPQ, corresponding to β-casein f(166-175); peptide MPFPKYPVEP, corresponding to β-casein f(124133); and peptide EPVLGPVRGPFP, corresponding to β-casein f(210-221), contained ACE-inhibitory activities. These peptides were chosen for chemical synthesis to confirm the ACE-inhibitory activity of the fractions. Chemically synthesized peptides displayed IC50 values in the range of 92 μM to 790 μM. Additionally, a simulated gastrointestinal digestion confirmed that the ACE-inhibitory 10-kDa L. animalis DPC6134 fermentation was resistant to a cocktail of digestive enzymes found in the gastrointestinal tract. PMID:17483275

Oxidation of β-blockers by birnessite: Kinetics, mechanism and effect of metal ions.

PubMed

Chen, Yong; Lu, Xiye; Liu, Lu; Wan, Dong; Chen, Huabin; Zhou, Danna; Sharma, Virender K

2018-03-01

Manganese dioxides are ubiquitous in natural waters, soils, and sediments and play an important role in oxidative transformation of organic pollutants. This work presents the kinetics of the oxidation of selected β-blockers, betaxolol, metoprolol, and atenolol by birnessite (δ-MnO 2 ) as a function of concentration of the β-blocker, dosage of δ-MnO 2 , and solution pH. The values of pseudo-first-order rate constants (k obs ) of β-blockers decreased in the order betaxolol > atenolol > metoprolol, which was positively correlated with their acid dissociation constants (K a ). Effect of series of metal ions (Fe 3+ , Cr 3+ , Al 3+ , Pb 2+ , Cu 2+ , Zn 2+ , Ni 2+ , Cd 2+ , Mg 2+ , and Ca 2+ ) on the degradation of β-blockers by δ-MnO 2 was systematically examined. All of these metal ions inhibited the oxidation reaction under the same constant ionic strength. The inhibition efficiency was positively correlated with the logarithm of stability constant of metal ions in aqueous solution (logK MeOH ). By LC-ESI-MS/MS analyses, the oxidation of β-blockers primarily involved hydroxylation and cleavage of the parent molecules to the short branched chain compounds. An electron transfer mechanism for the oxidation of β-blockers by δ-MnO 2 was proposed. The oxidation was initiated by the electron transfer from the nonbonding electrons on nitrogen (N-electrons) of β-blockers to δ-MnO 2 , followed by transformation of radical intermediates. These findings will help to understand the oxidation processes of β-blockers and predict the effect of metal ions on the removal of pollutants by δ-MnO 2 in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective and sensitive speciation analysis of Cr(VI) and Cr(III), at sub-μgL-1 levels in water samples by electrothermal atomic absorption spectrometry after electromembrane extraction.

PubMed

Tahmasebi, Zeinab; Davarani, Saied Saeed Hosseiny

2016-12-01

In this work, electromembrane extraction in combination with electrothermal atomic absorption spectrometry (ET-AAS) was investigated for speciation, preconcentration and quantification of Cr(VI) and Cr(III) in water samples through the selective complexation of Cr(VI) with 1,5-diphenylcarbazide (DPC) as a complexing agent. DPC reduces Cr(VI) to Cr(III) ions and then Cr(III) species are extracted based on electrokinetic migration of their cationic complex (Cr(III)-DPC) toward the negative electrode placed in the hollow fiber. Also, once oxidized to Cr(VI), Cr(III) ions in initial sample were determined by this procedure. The influence of extraction parameters such as pH, type of organic solvent, chelating agent concentration, stirring rate, extraction time and applied voltage were evaluated following a one-at-a-time optimization approach. Under optimized conditions, the extracted analyte was quantified by ETAAS, with an acceptable linearity in the range of 0.05-5ngmL -1 (R 2 value=0.996), and a repeatability (%RSD) between 3.7% and 12.2% (n=4) for 5.0 and 1.0ngmL -1 of Cr(VI), respectively. Also, we obtained an enrichment factor of 110 that corresponded to the recovery of 66%. The detection limit (S/N ratio of 3:1) was 0.02ngmL -1 . Finally, this new method was successfully employed to determine Cr(III) and Cr(VI) species in real water samples. Copyright © 2016. Published by Elsevier B.V.

DNA-Protein Cross-Links: Formation, Structural Identities, and Biological Outcomes.

PubMed

Tretyakova, Natalia Y; Groehler, Arnold; Ji, Shaofei

2015-06-16

Noncovalent DNA-protein interactions are at the heart of normal cell function. In eukaryotic cells, genomic DNA is wrapped around histone octamers to allow for chromosomal packaging in the nucleus. Binding of regulatory protein factors to DNA directs replication, controls transcription, and mediates cellular responses to DNA damage. Because of their fundamental significance in all cellular processes involving DNA, dynamic DNA-protein interactions are required for cell survival, and their disruption is likely to have serious biological consequences. DNA-protein cross-links (DPCs) form when cellular proteins become covalently trapped on DNA strands upon exposure to various endogenous, environmental and chemotherapeutic agents. DPCs progressively accumulate in the brain and heart tissues as a result of endogenous exposure to reactive oxygen species and lipid peroxidation products, as well as normal cellular metabolism. A range of structurally diverse DPCs are found following treatment with chemotherapeutic drugs, transition metal ions, and metabolically activated carcinogens. Because of their considerable size and their helix-distorting nature, DPCs interfere with the progression of replication and transcription machineries and hence hamper the faithful expression of genetic information, potentially contributing to mutagenesis and carcinogenesis. Mass spectrometry-based studies have identified hundreds of proteins that can become cross-linked to nuclear DNA in the presence of reactive oxygen species, carcinogen metabolites, and antitumor drugs. While many of these proteins including histones, transcription factors, and repair proteins are known DNA binding partners, other gene products with no documented affinity for DNA also participate in DPC formation. Furthermore, multiple sites within DNA can be targeted for cross-linking including the N7 of guanine, the C-5 methyl group of thymine, and the exocyclic amino groups of guanine, cytosine, and adenine. This structural complexity complicates structural and biological studies of DPC lesions. Two general strategies have been developed for creating DNA strands containing structurally defined, site-specific DPCs. Enzymatic methodologies that trap DNA modifying proteins on their DNA substrate are site specific and efficient, but do not allow for systematic studies of DPC lesion structure on their biological outcomes. Synthetic methodologies for DPC formation are based on solid phase synthesis of oligonucleotide strands containing protein-reactive unnatural DNA bases. The latter approach allows for a wider range of protein substrates to be conjugated to DNA and affords a greater flexibility for the attachment sites within DNA. In this Account, we outline the chemistry of DPC formation in cells, describe our recent efforts to identify the cross-linked proteins by mass spectrometry, and discuss various methodologies for preparing DNA strands containing structurally defined, site specific DPC lesions. Polymerase bypass experiments conducted with model DPCs indicate that the biological outcomes of these bulky lesions are strongly dependent on the peptide/protein size and the exact cross-linking site within DNA. Future studies are needed to elucidate the mechanisms of DPC repair and their biological outcomes in living cells.

DNA-Protein Cross-links: Formation, Structural Identities, and Biological Outcomes

PubMed Central

Tretyakova, Natalia Y.; Groehler, Arnold; Ji, Shaofei

2015-01-01

CONSPECTUS Non-covalent DNA-protein interactions are at the heart of normal cell function. In eukaryotic cells, genomic DNA is wrapped around histone octamers to allow for chromosomal packaging in the nucleus. Binding of regulatory protein factors to DNA directs replication, controls transcription, and mediates cellular responses to DNA damage. Because of their fundamental significance in all cellular processes involving DNA, dynamic DNA-protein interactions are required for cell survival, and their disruption is likely to have serious biological consequences. DNA-protein cross-links (DPCs) form when cellular proteins become covalently trapped on DNA strands upon exposure to various endogenous, environmental and chemotherapeutic agents. DPCs progressively accumulate in the brain and heart tissues as a result of endogenous exposure to reactive oxygen species and lipid peroxidation products, as well as normal cellular metabolism. A range of structurally diverse DPCs are found following treatment with chemotherapeutic drugs, transition metal ions, and metabolically activated carcinogens. Because of their considerable size and their helix-distorting nature, DPCs interfere with the progression of replication and transcription machineries and hence hamper the faithful expression of genetic information, potentially contributing to mutagenesis and carcinogenesis. Mass spectrometry-based studies have identified hundreds of proteins that can become cross-linked to nuclear DNA in the presence of reactive oxygen species, carcinogen metabolites, and antitumor drugs. While many of these proteins including histones, transcription factors, and repair proteins are known DNA binding partners, other gene products with no documented affinity for DNA also participate in DPC formation. Furthermore, multiple sites within DNA can be targeted for cross-linking including the N7 of guanine, the C-5 methyl group of thymine, and the exocyclic amino groups of guanine, cytosine, and adenine. This structural complexity complicates structural and biological studies of DPC lesions. Two general strategies have been developed for creating DNA strands containing structurally defined, site-specific DPCs. Enzymatic methodologies that trap DNA modifying proteins on their DNA substrate are site specific and efficient, but do not allow for systematic studies of DPC lesion structure on their biological outcomes. Synthetic methodologies for DPC formation are based on solid phase synthesis of oligonucleotide strands containing protein-reactive unnatural DNA bases. The latter approach allows for a wider range of protein substrates to be conjugated to DNA and affords a greater flexibility for the attachment sites within DNA. In this Account, we outline the chemistry of DPC formation in cells, describe our recent efforts to identify the cross-linked proteins by mass spectrometry, and discuss various methodologies for preparing DNA strands containing structurally defined, site specific DPC lesions. Polymerase bypass experiments conducted with model DPCs indicate that the biological outcomes of these bulky lesions are strongly dependent on the peptide/protein size and the exact cross-linking site within DNA. Future studies are needed to elucidate the mechanisms of DPC repair and their biological outcomes in living cells. PMID:26032357

Diffracting aperture based differential phase contrast for scanning X-ray microscopy.

PubMed

Kaulich, Burkhard; Polack, Francois; Neuhaeusler, Ulrich; Susini, Jean; di Fabrizio, Enzo; Wilhein, Thomas

2002-10-07

It is demonstrated that in a zone plate based scanning X-ray microscope, used to image low absorbing, heterogeneous matter at a mesoscopic scale, differential phase contrast (DPC) can be implemented without adding any additional optical component to the normal scheme of the microscope. The DPC mode is simply generated by an appropriate positioning and alignment of microscope apertures. Diffraction from the apertures produces a wave front with a non-uniform intensity. The signal recorded by a pinhole photo diode located in the intensity gradient is highly sensitive to phase changes introduced by the specimen to be recorded. The feasibility of this novel DPC technique was proven with the scanning X-ray microscope at the ID21 beamline of the European Synchrotron Radiation facility (ESRF) operated at 6 keV photon energy. We observe a differential phase contrast, similar to Nomarski's differential interference contrast for the light microscope, which results in a tremendous increase in image contrast of up to 20 % when imaging low absorbing specimen.

Decoding a Decision Process in the Neuronal Population of Dorsal Premotor Cortex.

PubMed

Rossi-Pool, Román; Zainos, Antonio; Alvarez, Manuel; Zizumbo, Jerónimo; Vergara, José; Romo, Ranulfo

2017-12-20

When trained monkeys discriminate the temporal structure of two sequential vibrotactile stimuli, dorsal premotor cortex (DPC) showed high heterogeneity among its neuronal responses. Notably, DPC neurons coded stimulus patterns as broader categories and signaled them during working memory, comparison, and postponed decision periods. Here, we show that such population activity can be condensed into two major coding components: one that persistently represented in working memory both the first stimulus identity and the postponed informed choice and another that transiently coded the initial sensory information and the result of the comparison between the two stimuli. Additionally, we identified relevant signals that coded the timing of task events. These temporal and task-parameter readouts were shown to be strongly linked to the monkeys' behavior when contrasted to those obtained in a non-demanding cognitive control task and during error trials. These signals, hidden in the heterogeneity, were prominently represented by the DPC population response. Copyright © 2017 Elsevier Inc. All rights reserved.

Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia.

PubMed

Leren, Ida S; Saberniak, Jørg; Majid, Eman; Haland, Trine F; Edvardsen, Thor; Haugaa, Kristina H

2016-02-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disease predisposing to malignant ventricular arrhythmias. We aimed to explore the incidence and severity of ventricular arrhythmias in patients with CPVT before the initiation of β-blocker treatment, when treated with β1-selective β-blockers, and when treated with nadolol. In this study, 34 patients with CPVT were included (mean age 34 ± 19 years; 15 (44%) women; 30 (88%) ryanodine receptor 2 variant positive). We performed 3 bicycle exercise stress tests in each patient: (1) before the initiation of β-blocker treatment, (2) after >6 weeks of treatment with β1-selective β-blockers and (3) after >6 weeks of treatment with nadolol. We recorded resting and maximum heart rates and the most severe ventricular arrhythmia occurring. Severity of arrhythmias was scored as 1 point for no arrhythmias or only single ventricular extrasystoles, 2 points for >10 ventricular extrasystoles per minute or bigeminy, 3 points for couplets, and 4 points for nonsustained ventricular tachycardia or sustained ventricular tachycardia. Resting heart rate was similar during treatment with nadolol and β1-selective β-blockers (54 ± 10 beats/min vs 56 ± 14 beats/min; P = .50), while maximum heart rate was lower during treatment with nadolol compared with β1-selective β-blockers (122 ± 21 beats/min vs 139 ± 24 beats/min; P = .001). Arrhythmias during exercise stress testing were less severe during treatment with nadolol compared with during treatment with β1-selective β-blockers (arrhythmic score 1.6 ± 0.9 vs 2.5 ± 0.8; P < .001) and before the initiation of β-blocker treatment (arrhythmic score 1.6 ± 0.9 vs 2.7 ± 0.9; P = .001); however, no differences were observed during treatment with β1-selective β-blockers compared with before the initiation of β-blocker treatment (arrhythmic score 2.5 ± 0.8 vs 2.7 ± 0.9; P = .46). The incidence and severity of ventricular arrhythmias decreased during treatment with nadolol compared with during treatment with β1-selective β-blockers. β1-Selective β-blockers did not change the occurrence or severity of arrhythmias compared with no medication. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis.

PubMed

Ham, Annelies C; van Dijk, Suzanne C; Swart, Karin M A; Enneman, Anke W; van der Zwaluw, Nikita L; Brouwer-Brolsma, Elske M; van Schoor, Natasja M; Zillikens, M Carola; Lips, Paul; de Groot, Lisette C P G M; Hofman, Albert; Witkamp, Renger F; Uitterlinden, André G; Stricker, Bruno H; van der Velde, Nathalie

2017-10-01

To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Data from two prospective studies were used, including community-dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying β-blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β-blocker use, their characteristics - selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism - and fall risk. The results of the studies were combined using meta-analyses. In total 2917 participants encountered a fall during a total follow-up time of 89 529 years. Meta-analysis indicated no association between use of any β-blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 [95% confidence interval (CI) 0.88-1.06]. Use of a selective β-blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83-1.01). Use of a nonselective β-blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01-1.48). Other β-blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk. Our study suggests that use of a nonselective β-blocker, contrary to selective β-blockers, is associated with an increased fall risk in an older population. In clinical practice, β-blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β-blocker in this age group, and the pros and cons for β-blocker classes should be taken into consideration. © 2017 The British Pharmacological Society.

Reduced-fat Cheddar and Swiss-type cheeses harboring exopolysaccharide-producing probiotic Lactobacillus mucosae DPC 6426.

PubMed

Ryan, P M; Burdíková, Z; Beresford, T; Auty, M A E; Fitzgerald, G F; Ross, R P; Sheehan, J J; Stanton, C

2015-12-01

Exopolysaccharide-producing Lactobacillus mucosae DPC 6426 was previously shown to have promising hypocholesterolemic activity in the atherosclerosis-prone apolipoprotein-E-deficient (apoE(-/-)) murine model. The aim of this study was to investigate the suitability of reduced-fat Cheddar and Swiss-type cheeses as functional (carrier) foods for delivery of this probiotic strain. All cheeses were manufactured at pilot-scale (500-L vats) in triplicate, with standard commercially available starters: for Cheddar, Lactococcus lactis; and for Swiss-type cheese, Streptococcus thermophilus, Lactobacillus helveticus, and Propionibacterium freudenreichii. Lactobacillus mucosae DPC 6426 was used as an adjunct culture during cheese manufacture, at a level of ~10(6) cfu·mL(-1) cheese milk (subsequently present in the cheese curd at>10(7) cfu·g(-1)). The adjunct strain remained viable at >5×10(7) cfu·g(-1) in both Swiss-type and Cheddar cheeses following ripening for 6 mo. Sensory analysis revealed that the presence of the adjunct culture imparted a more appealing appearance in Swiss-type cheese, but had no significant effect on the sensory characteristics of Cheddar cheeses. Moreover, the adjunct culture had no significant effect on cheese composition, proteolysis, pH, or instrumentally quantified textural characteristics of Cheddar cheeses. These data indicate that low-fat Swiss-type and Cheddar cheeses represent suitable food matrices for the delivery of the hypocholesterolemic Lactobacillus mucosae DPC 6426 in an industrial setting. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Scheduling Algorithms for Maximizing Throughput with Zero-Forcing Beamforming in a MIMO Wireless System

NASA Astrophysics Data System (ADS)

Foronda, Augusto; Ohta, Chikara; Tamaki, Hisashi

Dirty paper coding (DPC) is a strategy to achieve the region capacity of multiple input multiple output (MIMO) downlink channels and a DPC scheduler is throughput optimal if users are selected according to their queue states and current rates. However, DPC is difficult to implement in practical systems. One solution, zero-forcing beamforming (ZFBF) strategy has been proposed to achieve the same asymptotic sum rate capacity as that of DPC with an exhaustive search over the entire user set. Some suboptimal user group selection schedulers with reduced complexity based on ZFBF strategy (ZFBF-SUS) and proportional fair (PF) scheduling algorithm (PF-ZFBF) have also been proposed to enhance the throughput and fairness among the users, respectively. However, they are not throughput optimal, fairness and throughput decrease if each user queue length is different due to different users channel quality. Therefore, we propose two different scheduling algorithms: a throughput optimal scheduling algorithm (ZFBF-TO) and a reduced complexity scheduling algorithm (ZFBF-RC). Both are based on ZFBF strategy and, at every time slot, the scheduling algorithms have to select some users based on user channel quality, user queue length and orthogonality among users. Moreover, the proposed algorithms have to produce the rate allocation and power allocation for the selected users based on a modified water filling method. We analyze the schedulers complexity and numerical results show that ZFBF-RC provides throughput and fairness improvements compared to the ZFBF-SUS and PF-ZFBF scheduling algorithms.

Characterizing the structure-function relationship reveals the mode of action of a novel antimicrobial peptide, P1, from jumper ant Myrmecia pilosula.

PubMed

Tseng, Tien-Sheng; Tsai, Keng-Chang; Chen, Chinpan

2017-06-01

Microbial infections of antibiotic-resistant strains cause serious diseases and have a significant impact on public health worldwide, so novel antimicrobial drugs are urgently needed. Insect venoms, a rich source of bioactive components containing antimicrobial peptides (AMPs), are attractive candidates for new therapeutic agents against microbes. Recently, a novel peptide, P1, identified from the venom of the Australian jumper ant Myrmecia pilosula, showed potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, but its structure-function relationship is unknown. Here, we used biochemical and biophysical techniques coupled with computational simulations to explore the mode of action of P1 interaction with dodecylphosphocholine (DPC) micelles as a model membrane system. Our circular dichroism (CD) and NMR studies revealed an amphipathic α-helical structure for P1 upon interaction with DPC micelles. A paramagnetic relaxation enhancement approach revealed that P1 orients its α-helix segment (F6-G14) into DPC micelles. In addition, the α-helix segment could be essential for membrane permeabilization and antimicrobial activity. Moreover, the arginine residues R8, R11, and R15 significantly contribute to helix formation and membrane-binding affinity. The lysine residue K19 of the C-terminus functionally guides P1 to interact with DPC micelles in the early interaction stage. Our study provides insights into the mode of action of P1, which is valuable in modifying and developing potent AMPs as antibiotic drugs.

Renin angiotensin-aldosterone system (RAAS) blockers usage among type II diabetes mellitus patients-A Retrospective Study.

PubMed

Ng, Yen Ping; Balasubramanian, Ganesh Pandian; Heng, Yi Ping; Kalaiselvan, Meera; Teh, Yu Wen; Cheong, Kin Man; Hadi, Muhammad Faiz Bin Abdul; Othman, Rosmaliza Bt

2018-05-01

Recent data showed an alarming rise of new dialysis cases secondary to diabetic nephropathy despite the growing usage of RAAS blockers. Primary objective of this study is to explore the prevalence of RAAS blockers usage among type II diabetic patients, secondary objectives are to compare the prescribing pattern of RAAS blocker between primary and tertiary care center and to explore if the dose of RAAS blocker prescribed was at optimal dose as suggested by trials. This is a retrospective study conducted at one public tertiary referral hospital and one public health clinic in Sungai Petani, Kedah, Malaysia. RAAS blockers in T2DM patients was found to be 65%. In primary care, 14.3% of the RAAS blockers prescribed was ARB. Tertiary care had higher utilization of ARB, which was 42.9%. In primary care setting, the most commonly used ACEI were perindopril (92.4%) followed by enalapril (7.6%), meanwhile perindopril was the only ACEI being prescribed in tertiary care. The most prescribed ARB was irbesartan (63.6%) and telmisartan (54.2%) respectively in primary and tertiary care. Overall, 64.9% of RAAS blockers prescribed by both levels of care were found to be achieving the target dose as recommended in landmark trials. Crude odd ratio of prescribing RAAS blocker in primary care versus tertiary care was reported as 2.70 (95% CI: 1.49 to 4.91). RAAS blockers usage among T2DM patients was higher in primary care versus tertiary care settings. Majority of the patients did not receive optimal dose of RAAS blockers. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Point mutations in the tumor suppressor Smad4/DPC4 enhance its phosphorylation by GSK3 and reversibly inactivate TGF-β signaling

PubMed Central

Demagny, Hadrien; De Robertis, Edward M

2016-01-01

The tumor suppressor Smad4/DPC4 is an essential transcription factor in the TGF-β pathway and is frequently mutated or deleted in prostate, colorectal, and pancreatic carcinomas. We recently discovered that Smad4 activity and stability are regulated by the FGF/EGF and Wnt signaling pathways through a series of MAPK and GSK3 phosphorylation sites located in its linker region. In the present study, we report that loss-of-function associated with 2 point mutations commonly found in colorectal and pancreatic cancers results from enhanced Smad4 phosphorylation by GSK3, generating a phosphodegron that leads to subsequent β-TrCP–mediated polyubiquitination and proteasomal degradation. Using chemical GSK3 inhibitors, we show that Smad4 point mutant proteins can be stabilized and TGF-β signaling restored in cancer cells harboring such mutations. PMID:27308538

Mice Deficient in Surfactant Protein A (SP-A) and SP-D or in TLR2 Manifest Delayed Parturition and Decreased Expression of Inflammatory and Contractile Genes

PubMed Central

Montalbano, Alina P.; Hawgood, Samuel

2013-01-01

Previously we obtained compelling evidence that the fetus provides a critical signal for the initiation of term labor through developmental induction of surfactant protein (SP)-A expression by the fetal lung and secretion into amniotic fluid (AF). We proposed that interactions of AF macrophage (Mφ) Toll-like receptors (TLRs) with SP-A, at term, or bacterial components, at preterm, result in their activation and migration to the pregnant uterus. Herein the timing of labor in wild-type (WT) C57BL/6 mice was compared with mice homozygous null for TLR2, SP-A, SP-D, or doubly deficient in SP-A and SP-D. Interestingly, TLR2−/− females manifested a significant (P < 0.001) delay in timing of labor compared with WT as well as reduced expression of the myometrial contraction-associated protein (CAP) gene, connexin-43, and Mφ marker, F4/80, at 18.5 d postcoitum (dpc). Whereas in first pregnancies, SP-A−/−, SP-D−/−, and SP-A/D−/− females delivered at term (∼19.5 dpc), in second pregnancies, parturition was delayed by approximately 12 h in SP-A−/− (P = 0.07) and in SP-A/D−/− (P <0.001) females. Myometrium of SP-A/D−/− females expressed significantly lower levels of IL-1β, IL-6, and CAP genes, connexin-43, and oxytocin receptor at 18.5 dpc compared with WT. F4/80+ AF Mφs from TLR2−/− and SP-A/D−/− mice expressed significantly lower levels of both proinflammatory and antiinflammatory activation markers (e.g. IL-1β, IL-6, ARG1, YM1) compared with gestation-matched WT AF Mφs. These novel findings suggest that the pulmonary collectins acting via TLR2 serve a modulatory role in the timing of labor; their relative impact may be dependent on parity. PMID:23183169

Direct Visualization of Local Electromagnetic Field Structures by Scanning Transmission Electron Microscopy.

PubMed

Shibata, Naoya; Findlay, Scott D; Matsumoto, Takao; Kohno, Yuji; Seki, Takehito; Sánchez-Santolino, Gabriel; Ikuhara, Yuichi

2017-07-18

The functional properties of materials and devices are critically determined by the electromagnetic field structures formed inside them, especially at nanointerface and surface regions, because such structures are strongly associated with the dynamics of electrons, holes and ions. To understand the fundamental origin of many exotic properties in modern materials and devices, it is essential to directly characterize local electromagnetic field structures at such defect regions, even down to atomic dimensions. In recent years, rapid progress in the development of high-speed area detectors for aberration-corrected scanning transmission electron microscopy (STEM) with sub-angstrom spatial resolution has opened new possibilities to directly image such electromagnetic field structures at very high-resolution. In this Account, we give an overview of our recent development of differential phase contrast (DPC) microscopy for aberration-corrected STEM and its application to many materials problems. In recent years, we have developed segmented-type STEM detectors which divide the detector plane into 16 segments and enable simultaneous imaging of 16 STEM images which are sensitive to the positions and angles of transmitted/scattered electrons on the detector plane. These detectors also have atomic-resolution imaging capability. Using these segmented-type STEM detectors, we show DPC STEM imaging to be a very powerful tool for directly imaging local electromagnetic field structures in materials and devices in real space. For example, DPC STEM can clearly visualize the local electric field variation due to the abrupt potential change across a p-n junction in a GaAs semiconductor, which cannot be observed by normal in-focus bright-field or annular type dark-field STEM imaging modes. DPC STEM is also very effective for imaging magnetic field structures in magnetic materials, such as magnetic domains and skyrmions. Moreover, real-time imaging of electromagnetic field structures can now be realized through very fast data acquisition, processing, and reconstruction algorithms. If we use DPC STEM for atomic-resolution imaging using a sub-angstrom size electron probe, it has been shown that we can directly observe the atomic electric field inside atoms within crystals and even inside single atoms, the field between the atomic nucleus and the surrounding electron cloud, which possesses information about the atomic species, local chemical bonding and charge redistribution between bonded atoms. This possibility may open an alternative way for directly visualizing atoms and nanostructures, that is, seeing atoms as an entity of electromagnetic fields that reflect the intra- and interatomic electronic structures. In this Account, the current status of aberration-corrected DPC STEM is highlighted, along with some applications in real material and device studies.

Transport via SLC5A8 (SMCT1) Is Obligatory for 2-Oxothiazolidine-4-Carboxylate to Enhance Glutathione Production in Retinal Pigment Epithelial Cells

PubMed Central

Babu, Ellappan; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Coothankandaswamy, Veena; Smith, Sylvia B.; Boettger, Thomas; Ganapathy, Vadivel

2011-01-01

Purpose. To evaluate the role of SLC5A8 in the transport of 2-oxothiazolidine-4-carboxylate (OTC) and to determine whether OTC augments glutathione production in RPE cells, thereby providing protection against oxidative stress. Methods. SLC5A8-mediated transport of OTC was monitored in Xenopus laevis oocytes by electrophysiological means. Saturation kinetics, Na+-activation kinetics, and inhibition by ibuprofen were analyzed by monitoring OTC-induced currents as a measure of transport activity. Oxidative stress was induced in ARPE-19 cells and primary RPE cells isolated from wild type and Slc5a8-/- mouse retinas using H2O2, and the effects of OTC on cell death and intracellular glutathione concentration were examined. Results. Heterologous expression of human SLC5A8 in X. laevis oocytes induced Na+-dependent inward currents in the presence of OTC under voltage-clamp conditions. The transport of OTC via SLC5A8 was saturable, with a Kt of 104 ± 3 μM. The Na+-activation kinetics was sigmoidal with a Hill coefficient of 1.9 ± 0.1, suggesting involvement of two Na+ in the activation process. Ibuprofen, a blocker of SLC5A8, inhibited SLC5A8-mediated OTC transport; the concentration necessary for half-maximal inhibition was 17 ± 1 μM. OTC increased glutathione levels and protected ARPE-19 and primary RPE cells isolated from wild type mouse retinas from H2O2-induced cell death. These effects were abolished in primary RPE isolated from Slc5a8-/- mouse retinas. Conclusions. OTC is a transportable substrate for SLC5A8. OTC augments glutathione production in RPE cells, thereby protecting them from oxidative damage. Transport via SLC5A8 is obligatory for this process. PMID:21508099

Specific Binding of Adamantane Drugs and Direction of their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy

PubMed Central

Cady, Sarah D.; Wang, Jun; Wu, Yibing; DeGrado, William F.; Hong, Mei

2011-01-01

The transmembrane domain of the influenza M2 protein (M2TM) forms a tetrameric proton channel important for the virus lifecycle. The proton-channel activity is inhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bind specifically to the pore of M2TM near Ser31. However, whether the polar amine points to the N- or C-terminus of the channel has not yet been determined. Elucidating the polar group direction will shed light on the mechanism by which drug binding inhibits this proton channel and will facilitate rational design of new inhibitors. In this study, we determine the polar amine direction using M2TM reconstituted in lipid bilayers as well as DPC micelles. 13C-2H rotational-echo double-resonance NMR experiments of 13C-labeled M2TM and methyl-deuterated rimantadine in lipid bilayers showed that the polar amine pointed to the C-terminus of the channel, with the methyl group close to Gly34. Solution NMR experiments of M2TM in dodecylphosphocholine (DPC) micelles indicate that drug binding causes significant chemical shift perturbations of the protein that are very similar to those seen for M2TM and M2(18–60) bound to lipid bilayers. Specific 2H-labeling of the drugs permitted the assignment of drug-protein cross peaks, which indicate that amantadine and rimantadine bind to the pore in the same fashion as for bilayer-bound M2TM. These results strongly suggest that adamantyl inhibition of M2TM is achieved not only by direct physical occlusion of the pore but also by perturbing the equilibrium constant of the proton-sensing residue His37. The reproduction of the pharmacologically relevant specific pore-binding site in DPC micelles, which was not observed with a different detergent, DHPC, underscores the significant influence of the detergent environment on the functional structure of membrane proteins. PMID:21381693

Beta-blockers for hypertension.

PubMed

Wiysonge, C S; Bradley, H; Mayosi, B M; Maroney, R; Mbewu, A; Opie, L H; Volmink, J

2007-01-24

Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs. To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts. We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older. At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I(2)) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance. Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I(2)=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I(2)=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I(2)=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I(2)=0%; ARI=0.6%, NNH=180). There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I(2)=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I(2)=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I(2)=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs. The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.

A Time Study of Plastic Surgery Residents.

PubMed

Lau, Frank H; Sinha, Indranil; Jiang, Wei; Lipsitz, Stuart R; Eriksson, Elof

2016-05-01

Resident work hours are under scrutiny and have been subject to multiple restrictions. The studies supporting these changes have not included data on surgical residents. We studied the workday of a team of plastic surgery residents to establish prospective time-study data of plastic surgery (PRS) residents at a single tertiary-care academic medical center. Five trained research assistants observed all residents (n = 8) on a PRS service for 10 weeks and produced minute-by-minute activity logs. Data collection began when the team first met in the morning and continued until the resident being followed completed all non-call activities. We analyzed our data from 3 perspectives: 1) time spent in direct patient care (DPC), indirect patient care, and didactic activities; 2) time spent in high education-value activities (HEAs) versus low education-value activities; and 3) resident efficiency. We defined HEAs as activities that surgeons must master; other activities were LEAs. We quantified resident efficiency in terms of time fragmentation and time spent waiting. A total of 642.4 hours of data across 50 workdays were collected. Excluding call, residents worked an average of 64.2 hours per week. Approximately 50.7% of surgical resident time was allotted to DPC, with surgery accounting for the largest segment of this time (34.8%). Time spent on HEAs demonstrated trended upward with higher resident level (P = 0.086). Time in spent in surgery was significantly associated with higher resident levels (P < 0.0001); 57.7% of activities require 4 minutes or less, suggesting that resident work was highly fragmented. Residents spent 10.7% of their workdays waiting for other services. In this first-time study of PRS residents, we found that compared with medicine trainees, surgical residents spent 3.23 times more time on DPC. High education-value activities comprised most of our residents' workdays. Surgery was the leading component of both DPC and HEAs. Our residents were highly efficient and fragmented, with the majority of all activities requiring 4 minutes or less. Residents spent a large portion of their time waiting for other services. In light of these data, we suggest that future changes to residency programs be pilot tested, with preimplantation and postimplementation time studies performed to quantify the changes' impact.

Selective degradation of thymidine and thymine deoxynucleotides

PubMed Central

Burton, K.; Riley, W. T.

1966-01-01

1. Osmium tetroxide in dilute ammonia oxidizes various pyrimidine nucleosides at different rates. Thymidine is oxidized about 45 times as fast as deoxycytidine. The phosphate groups may be eliminated from oxidized thymine nucleotides by successive treatments with alkali and then with diphenylamine in aqueous formic acid. The reactions can be applied to the selective degradation of thymidine in oligodeoxynucleotides. PMID:5938667

Free radical reaction characteristics of coal low-temperature oxidation and its inhibition method.

PubMed

Li, Zenghua; Kong, Biao; Wei, Aizhu; Yang, Yongliang; Zhou, Yinbo; Zhang, Lanzhun

2016-12-01

Study on the mechanism of coal spontaneous combustion is significant for controlling fire disasters due to coal spontaneous combustion. The free radical reactions can explain the chemical process of coal at low-temperature oxidation. Electron spin resonance (ESR) spectroscopy was used to measure the change rules of the different sorts and different granularity of coal directly; ESR spectroscopy chart of free radicals following the changes of temperatures was compared by the coal samples applying air and blowing nitrogen, original coal samples, dry coal samples, and demineralized coal samples. The fragmentation process was the key factor of producing and initiating free radical reactions. Oxygen, moisture, and mineral accelerated the free radical reactions. Combination of the free radical reaction mechanism, the mechanical fragmentation leaded to the elevated CO concentration, fracturing of coal pillar was more prone to spontaneous combustion, and spontaneous combustion in goaf accounted for a large proportion of the fire in the mine were explained. The method of added diphenylamine can inhibit the self-oxidation of coal effectively, the action mechanism of diphenylamine was analyzed by free radical chain reaction, and this research can offer new method for the development of new flame retardant.

[Examination of diagnosis procedure combination survey data that influence function evaluation coefficient II].

PubMed

Nakajima, Hisato; Yano, Kouya; Nagasawa, Kaoko; Kobayashi, Eiji; Yokota, Kuninobu

2015-01-01

On the basis of Diagnosis Procedure Combination (DPC) survey data, the factors that increase the value of function evaluation coefficient II were considered. A total of 1,505 hospitals were divided into groups I, II, and III, and the following items were considered. 1. Significant differences in function evaluation coefficient II and DPC survey data. 2. Examination of using the Mahalanobis-Taguchi (MT) method. 3. Correlation between function evaluation coefficient II and each DPC survey data item. 1. Function evaluation coefficient II was highest in group II. Group I hospitals showed the highest bed capacity, and numbers of hospitalization days, operations, chemotherapies, radiotherapies and general anesthesia procedures. 2. Using the MT method, we found that the number of ambulance conveyances was effective factor in group I hospitals, the number of general anesthesia procedures was effective factor in group II hospitals, and the bed capacity was effective factor in group III hospitals. 3. In group I hospitals, function evaluation coefficient II significantly correlated to the numbers of ambulance conveyances and chemotherapies. In group II hospitals, function evaluation coefficient II significantly correlated to bed capacity, the numbers of ambulance conveyances, hospitalization days, operations, general anesthesia procedures, and mean hospitalization days. In group III hospitals, function evaluation coefficient II significantly correlated to all items. The factors that improve the value of function evaluation coefficient II were the increases in the numbers of ambulance conveyances, chemotherapies and radiotherapies in group I hospitals, increases in the numbers of hospitalization days, operations, ambulance conveyances and general anesthesia procedures in group II hospitals, and increases in the numbers of hospitalization days, operations and ambulance conveyances. These results indicate that the profit of a hospital will increase, which will lead to medical services of good quality.

S100A8, An Oocyte-Specific Chemokine, Directs the Migration of Ovarian Somatic Cells During Mouse Primordial Follicle Assembly.

PubMed

Teng, Zhen; Wang, Chao; Wang, Yijing; Huang, Kun; Xiang, Xi; Niu, Wanbao; Feng, Lizhao; Zhao, Lihua; Yan, Hao; Zhang, Hua; Xia, Guoliang

2015-12-01

In the mammalian ovaries, the primordial follicle pool determines the reproductive capability over the lifetime of a female. The primordial follicle is composed of two cell members, namely the oocyte and the pre-granulosa cells that encircle the oocyte. However, it is unclear what factors are involved in the reorganization of the two distinct cells into one functional unit. This study was performed to address this issue. Firstly, in an in vitro reconstruction system, dispersed ovarian cells from murine fetal ovaries at 19.0 days post coitum (dpc) reassembled into follicle-like structures, independent of the physical distance between the cells, implying that either oocytes or ovarian somatic cells (OSCs) were motile. We then carried out a series of transwell assay experiments, and determined that it was in fact 19.0 dpc OSCs (as opposed to oocytes), which exhibited a significant chemotactic response to both fetal bovine serum and oocytes themselves. We observed that S100A8, a multi-functional chemokine, may participate in the process as it is mainly expressed in oocytes within the cysts/plasmodia. S100A8 significantly promoted the number of migrating OSCs by 2.5 times in vitro, of which 66.9% were FOXL2 protein-positive cells, implying that the majority of motile OSCs were pre-granulosa cells. In addition, an S100A8-specific antibody inhibited the formation of follicle-like reconstruction cell mass in vitro. And, the primordial follicle formation was reduced when S100a8-specific siRNA was applied onto in vitro cultured 17.5 dpc ovary. Therefore, S100A8 could be a chemokine of oocyte origin, which attracts OSCs to form the primordial follicles. © 2015 Wiley Periodicals, Inc.

Backbone dynamics of the antifungal Psd1 pea defensin and its correlation with membrane interaction by NMR spectroscopy.

PubMed

de Medeiros, Luciano Neves; Angeli, Renata; Sarzedas, Carolina G; Barreto-Bergter, Eliana; Valente, Ana Paula; Kurtenbach, Eleonora; Almeida, Fabio C L

2010-02-01

Plant defensins are cysteine-rich cationic peptides, components of the innate immune system. The antifungal sensitivity of certain exemplars was correlated to the level of complex glycosphingolipids in the membrane of fungi strains. Psd1 is a 46 amino acid residue defensin isolated from pea seeds which exhibit antifungal activity. Its structure is characterized by the so-called cysteine-stabilized alpha/beta motif linked by three loops as determined by two-dimensional NMR. In the present work we explored the measurement of heteronuclear Nuclear Overhauser Effects, R1 and R2 (15)N relaxation ratios, and chemical shift to probe the backbone dynamics of Psd1 and its interaction with membrane mimetic systems with phosphatidylcholine (PC) or dodecylphosphocholine (DPC) with glucosylceramide (CMH) isolated from Fusarium solani. The calculated R2 values predicted a slow motion around the highly conserved among Gly12 residue and also in the region of the Turn3 His36-Trp38. The results showed that Psd1 interacts with vesicles of PC or PC:CMH in slightly different forms. The interaction was monitored by chemical shift perturbation and relaxation properties. Using this approach we could map the loops as the binding site of Psd1 with the membrane. The major binding epitope showed conformation exchange properties in the mus-ms timescale supporting the conformation selection as the binding mechanism. Moreover, the peptide corresponding to part of Loop1 (pepLoop1: Gly12 to Ser19) is also able to interact with DPC micelles acquiring a stable structure and in the presence of DPC:CMH the peptide changes to an extended conformation, exhibiting NOE mainly with the carbohydrate and ceramide parts of CMH. Copyright 2009 Elsevier B.V. All rights reserved.

Effects of endocrine disruptors on imprinted gene expression in the mouse embryo

PubMed Central

Tran, Diana A; Rivas, Guillermo E; Singh, Purnima; Pfeifer, Gerd P

2011-01-01

Environmental endocrine disruptors (EDs) are synthetic chemicals that resemble natural hormones and are known to cause epigenetic perturbations. EDs have profound effects on development and fertility. Imprinted genes had been identified as candidate susceptibility loci to environmental insults because they are functionally haploid, and because the imprints undergo epigenetic resetting between generations. To screen for possible epigenetic perturbations caused by EDs at imprinted loci, we treated pregnant mice daily between 8.5 and 12.5 days post coitum (dpc) with di-(2-ethylhexyl)-phthalate (DEHP), bisphenol A (BPA), vinclozolin (VZ) or control oil vehicle. After isolating RNA from the placenta, yolk sac, amnion, head, body, heart, liver, lung, stomach and intestines of 13.5 dpc embryos we measured the allele-specific expression of 39 imprinted transcripts using multiplex single nucleotide primer extension (SNuPE) assays. In this representative data set we identified only a small number of transcripts that exhibited a substantial relaxation of imprinted expression with statistical significance: Slc22a18 with 10% relaxation in the embryo after BPA treatment; Rtl1as with 11 and 16% relaxation in the lung and placenta, respectively after BPA treatment; and Rtl1 with 12% relaxation in the yolk sac after DEHP treatment. Additionally, the standard deviation of allele-specificity increased in various organs after ED treatment for several transcripts including Igf2r, Rasgrf1, Usp29, Slc38a4 and Xist. Our data suggest that the maintenance of strongly biased monoallelic expression of imprinted genes is generally insensitive to EDs in the 13.5 dpc embryo and extra-embryonic organs, but is not immune to those effects. PMID:21636974

NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion.

PubMed

Mahajan, Mukesh; Chatterjee, Deepak; Bhuvaneswari, Kannaian; Pillay, Shubhadra; Bhattacharjya, Surajit

2018-02-01

The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. 15 N{ 1 H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.

PubMed

Oster, Michael; Murani, Eduard; Metges, Cornelia C; Ponsuksili, Siriluck; Wimmers, Klaus

2012-08-17

Inadequate maternal protein supply during gestation represents an environmental factor that affects physiological signaling pathways with long-term consequences for growth, function, and structure of various tissues. Hypothesizing that the offspring's transcriptome is persistently altered by maternal diets, we used a porcine model to monitor the longitudinal expression changes in muscle to identify pathways relevant to fetal initiation of postnatal growth and development. German Landrace gilts were fed isoenergetic gestational diets containing 6.5% (LP) or 12.1% protein. The longissimus dorsi samples were collected from offspring at 94 days postconception (dpc) and 1, 28, and 188 days postnatum (dpn) for expression profiling. At 94 dpc, 1 dpn, and 28 dpn relatively few transcripts (<130) showed an altered abundance between the dietary groups. In fact, at 94 dpc genes of G2/M checkpoint regulation and mitotic roles of Polo-like kinases showed lowered transcript abundance in LP. At 188 dpn 677 transcripts were altered including those related to oxidative phosphorylation, citrate cycle, fatty acid metabolism (higher abundance in LP) and cell cycle regulation (lower abundance in LP). Correspondingly, transcriptional alterations during pre and postnatal development differed considerably among dietary groups, particularly for genes related to cell cycle regulation (G1/S and G2/M checkpoint regulation; cyclines), growth factor signaling (GH, IGF1, mTOR, RAN, VEGF, INSR), lipid metabolism, energy metabolism, and nucleic acid metabolism. In skeletal muscle, fetal programming related to maternal LP diets disturbed gene expression in growth-related pathways into adulthood. Diet-dependent gene expression may hamper proper development, thereby affecting signaling pathways related to energy utilization.

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.

PubMed

Moriya, Toshiyuki; Kimura, Wataru; Semba, Shuho; Sakurai, Fumiaki; Hirai, Ichiro; Ma, Jinfeng; Fuse, Akira; Maeda, Kunihiko; Yamakawa, Mitsunori

2005-01-01

Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015). In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.

Patterns of beta-blocker intensification in ambulatory heart failure patients and short-term association with hospitalization

PubMed Central

2012-01-01

Background In response to the short-term negative inotropic and chronotropic effects of β-blockers, heart failure (HF) guidelines recommend initiating β-blockers at low dose with gradual uptitration as tolerated to doses used in clinical trials. However, patterns and safety of β-blocker intensification in routine practice are poorly described. Methods We described β-blocker intensification among Kaiser Colorado enrollees with a primary discharge diagnosis of HF between 2001–2009. We then assessed β-blocker intensification in the 30 days prior to first hospital readmission for cases compared to the same time period following index hospitalization for non-rehospitalized matched controls. In separate analysis of the subgroup initiated on β-blocker after index hospital discharge, we compared adjusted rates of 30-day hospitalization following initiation of high versus low dose β-blocker. Results Among 3,227 patients, median age was 76 years and 37% had ejection fraction ≤40% (LVSD). During a median follow up of 669 days, 14% were never on β-blocker, 21% were initiated on β-blocker, 43% were discharged on β-blocker but never uptitrated, and 22% had discharge β-blocker uptitrated; 63% were readmitted and 49% died. β-blocker intensification occurred in the 30 days preceding readmission for 39 of 1,674 (2.3%) readmitted cases compared to 27 (1.6%) of matched controls (adjusted OR 1.36, 95% CI 0.81-2.27). Among patients initiated on therapy, readmission over the subsequent 30 days occurred in 6 of 155 (3.9%) prescribed high dose and 9 of 513 (1.8%) prescribed low dose β-blocker (adjusted OR 3.10, 95% CI 1.02-9.40). For the subgroup with LVSD, findings were not significantly different. Conclusion While β-blockers were intensified in nearly half of patients following hospital discharge and high starting dose was associated with increased readmission risk, the prevailing finding was that readmission events were rarely preceded by β-blocker intensification. These data suggest that β-blocker intensification is not a major precipitant of hospitalization, provided recommended dosing is followed. PMID:22709128

Optimal therapy for stress gastritis.

PubMed Central

Maier, R V; Mitchell, D; Gentilello, L

1994-01-01

OBJECTIVE: The authors compared the results of sucralfate versus H2 blocker +/- antacid as prophylaxis for stress ulceration in an intensive care unit patient population. SUMMARY BACKGROUND DATA: Stress ulceration carries high morbidity and mortality for the patient who is critically ill. Gastric acid neutralization is an effective prophylaxis. The impact of increased gastric colonization with bacterial pathogens on nosocomial pneumonia after acid neutralization is unclear. The efficacy of sucralfate prophylaxis for stress ulceration and its the effect on the nosocomial pneumonia rate is controversial. The financial implications of sucralfate prophylaxis versus H2 blocker-based acid neutralization therapy has not been studied. METHODS: Ninety-eight injured patients who were critically ill and who required intubation and intensive care unit (ICU) support for at least 72 hours without gastric feeding were randomized and received either maximal H2 blocker infusion therapy (continuous infusion of ranitidine at 0.25 mg/kg/hr after a loading dose of 0.5 mg/kg) plus antacids (for persistent pH < 4) or sucralfate (1 g every 6 hours via nasogastric tube) for stress ulcer prophylaxis. Efficacy in preventing stress ulcer complications was determined. The impact of each therapeutic approach on development of nosocomial pneumonia was evaluated. The charges/cost for each approach was analyzed. RESULTS: Heme-positive gastric aspirates occurred in 99% of the patients, whereas 12 (7 in the H2 blocker group and 5 in the sucralfate group) were grossly positive for blood. However, only one from each group required transfusion, and one in the H2 blocker group required operation. Gastric colonization preceded tracheobronchial colonization in five patients in the H2 blocker group and one patient in the sucralfate group; simultaneous gastric/oropharyngeal colonization preceded positive tracheobronchial growth in six patients who received H2 blocker and one patient who received sucralfate. The overall pneumonia rate was 27.5% in the H2 blocker group and 20.8% in the sucralfate group (p = 0.48). Days on ventilator were 13.5 versus 9.1, (p = 0.06), ICU lengths of stay were 14.7 versus 10.2 (p = 0.06), and hospital lengths of stay were 27.8 versus 20.0 (p = 0.029) for the H2 blocker group and sucralfate group, respectively. Based on current charges and protocols for optimal H2 blocker and sucralfate prophylaxis, use of sucralfate rather than H2 blockers would decrease the annual cost by more than $30,000 per bed. CONCLUSIONS: Sucralfate is as efficacious as maximal H2 blocker therapy for stress ulceration prophylaxis, and may have a beneficial effect on the incidence of nosocomial pneumonia. Sucralfate has a major reduction on nursing requirements for stress ulcer prophylaxis and would save approximately $30,000 per ICU bed per year in patient charges. PMID:8092901

Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi; Medical Research Center, Oulu University Hospital, Oulu; Alhonen, Leena

Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism andmore » uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.« less

Improving documentation of a beta-blocker quality measure through an anesthesia information management system and real-time notification of documentation errors.

PubMed

Nair, Bala G; Peterson, Gene N; Newman, Shu-Fang; Wu, Wei-Ying; Kolios-Morris, Vickie; Schwid, Howard A

2012-06-01

Continuation of perioperative beta-blockers for surgical patients who are receiving beta-blockers prior to arrival for surgery is an important quality measure (SCIP-Card-2). For this measure to be considered successful, name, date, and time of the perioperative beta-blocker must be documented. Alternately, if the beta-blocker is not given, the medical reason for not administering must be documented. Before the study was conducted, the institution lacked a highly reliable process to document the date and time of self-administration of beta-blockers prior to hospital admission. Because of this, compliance with the beta-blocker quality measure was poor (-65%). To improve this measure, the anesthesia care team was made responsible for documenting perioperative beta-blockade. Clear documentation guidelines were outlined, and an electronic Anesthesia Information Management System (AIMS) was configured to facilitate complete documentation of the beta-blocker quality measure. In addition, real-time electronic alerts were generated using Smart Anesthesia Messenger (SAM), an internally developed decision-support system, to notify users concerning incomplete beta-blocker documentation. Weekly compliance for perioperative beta-blocker documentation before the study was 65.8 +/- 16.6%, which served as the baseline value. When the anesthesia care team started documenting perioperative beta-blocker in AIMS, compliance was 60.5 +/- 8.6% (p = .677 as compared with baseline). Electronic alerts with SAM improved documentation compliance to 94.6 +/- 3.5% (p < .001 as compared with baseline). To achieve high compliance for the beta-blocker measure, it is essential to (1) clearly assign a medical team to perform beta-blocker documentation and (2) enhance features in the electronic medical systems to alert the user concerning incomplete documentation.

iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration.

PubMed

Zhang, Huan; Zhu, Ning-Xia; Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

2016-01-01

Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles.

Role of chloride ions in the promotion of auxin-induced growth of maize coleoptile segments.

PubMed

Burdach, Zbigniew; Kurtyka, Renata; Siemieniuk, Agnieszka; Karcz, Waldemar

2014-10-01

The mechanism of auxin action on ion transport in growing cells has not been determined in detail. In particular, little is known about the role of chloride in the auxin-induced growth of coleoptile cells. Moreover, the data that do exist in the literature are controversial. This study describes experiments that were carried out with maize (Zea mays) coleoptile segments, this being a classical model system for studies of plant cell elongation growth. Growth kinetics or growth and pH changes were recorded in maize coleoptiles using two independent measuring systems. The growth rate of the segments was measured simultaneously with medium pH changes. Membrane potential changes in parenchymal cells of the segments were also determined for chosen variants. The question of whether anion transport is involved in auxin-induced growth of maize coleoptile segments was primarily studied using anion channel blockers [anthracene-9-carboxylic acid (A-9-C) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS)]. In addition, experiments in which KCl was replaced by KNO3 were also performed. Both anion channel blockers, added at 0·1 mm, diminished indole-3-acetic acid (IAA)-induced elongation growth by ~30 %. Medium pH changes measured simultaneously with growth indicated that while DIDS stopped IAA-induced proton extrusion, A-9-C diminished it by only 50 %. Addition of A-9-C to medium containing 1 mm KCl did not affect the characteristic kinetics of IAA-induced membrane potential changes, while in the presence of 10 mm KCl the channel blocker stopped IAA-induced membrane hyperpolarization. Replacement of KCl with KNO3 significantly decreased IAA-induced growth and inhibited proton extrusion. In contrast to the KCl concentration, the concentration of KNO3 did not affect the growth-stimulatory effect of IAA. For comparison, the effects of the cation channel blocker tetraethylammonium chloride (TEA-Cl) on IAA-induced growth and proton extrusion were also determined. TEA-Cl, added 1 h before IAA, caused reduction of growth by 49·9 % and inhibition of proton extrusion. These results suggest that Cl(-) plays a role in the IAA-induced growth of maize coleoptile segments. A possible mechanism for Cl(-) uptake during IAA-induced growth is proposed in which uptake of K(+) and Cl(-) ions in concert with IAA-induced plasma membrane H(+)-ATPase activity changes the membrane potential to a value needed for turgor adjustment during the growth of maize coleoptile cells. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial.

PubMed

Holroyd, Kenneth A; Cottrell, Constance K; O'Donnell, Francis J; Cordingley, Gary E; Drew, Jana B; Carlson, Bruce W; Himawan, Lina

2010-09-29

To determine if the addition of preventive drug treatment (β blocker), brief behavioural migraine management, or their combination improves the outcome of optimised acute treatment in the management of frequent migraine. Randomised placebo controlled trial over 16 months from July 2001 to November 2005. Two outpatient sites in Ohio, USA. 232 adults (mean age 38 years; 79% female) with diagnosis of migraine with or without aura according to International Headache Society classification of headache disorders criteria, who recorded at least three migraines with disability per 30 days (mean 5.5 migraines/30 days), during an optimised run-in of acute treatment. Addition of one of four preventive treatments to optimised acute treatment: β blocker (n=53), matched placebo (n=55), behavioural migraine management plus placebo (n=55), or behavioural migraine management plus β blocker (n=69). The primary outcome was change in migraines/30 days; secondary outcomes included change in migraine days/30 days and change in migraine specific quality of life scores. Mixed model analysis showed statistically significant (P≤0.05) differences in outcomes among the four added treatments for both the primary outcome (migraines/30 days) and the two secondary outcomes (change in migraine days/30 days and change in migraine specific quality of life scores). The addition of combined β blocker and behavioural migraine management (-3.3 migraines/30 days, 95% confidence interval -3.2 to -3.5), but not the addition of β blocker alone (-2.1 migraines/30 days, -1.9 to -2.2) or behavioural migraine management alone (-2.2 migraines migraines/30 days, -2.0 to -2.4), improved outcomes compared with optimised acute treatment alone (-2.1 migraines/30 days, -1.9 to -2.2). For a clinically significant (≥50% reduction) in migraines/30 days, the number needed to treat for optimised acute treatment plus combined β blocker and behavioural migraine management was 3.1 compared with optimised acute treatment alone, 2.6 compared with optimised acute treatment plus β blocker, and 3.1 compared with optimised acute treatment plus behavioural migraine management. Results were consistent for the two secondary outcomes, and at both month 10 (the primary endpoint) and month 16. The addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment. Combined β blocker treatment and behavioural migraine management may improve outcomes in the treatment of frequent migraine. Clinical trials NCT00910689.

A reconstruction method for cone-beam differential x-ray phase-contrast computed tomography.

PubMed

Fu, Jian; Velroyen, Astrid; Tan, Renbo; Zhang, Junwei; Chen, Liyuan; Tapfer, Arne; Bech, Martin; Pfeiffer, Franz

2012-09-10

Most existing differential phase-contrast computed tomography (DPC-CT) approaches are based on three kinds of scanning geometries, described by parallel-beam, fan-beam and cone-beam. Due to the potential of compact imaging systems with magnified spatial resolution, cone-beam DPC-CT has attracted significant interest. In this paper, we report a reconstruction method based on a back-projection filtration (BPF) algorithm for cone-beam DPC-CT. Due to the differential nature of phase contrast projections, the algorithm restrains from differentiation of the projection data prior to back-projection, unlike BPF algorithms commonly used for absorption-based CT data. This work comprises a numerical study of the algorithm and its experimental verification using a dataset measured with a three-grating interferometer and a micro-focus x-ray tube source. Moreover, the numerical simulation and experimental results demonstrate that the proposed method can deal with several classes of truncated cone-beam datasets. We believe that this feature is of particular interest for future medical cone-beam phase-contrast CT imaging applications.

Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity.

PubMed

Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L

2017-04-01

Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p < 0.0001); 1225 (10.1%) beta-blocker users and 658 (5.4%) nonbeta-blocker users were prescribed a psychotropic drug (p < 0.0001); and 16 (0.13%) beta-blocker users and 6 (0.05%) nonbeta-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1.57-1.79], p < 0.0001), other psychotropic medication use (HR, 1.93 [95% CI, 1.76-2.12] p < 0.0001), and suicide attempts (HR, 2.67 [95% CI, 1.04-6.82] p = 0.04). In healthy students, use of beta-blockers during the exam period was associated with an increased risk of psychiatric outcomes and might identify psychologically vulnerable students who need special attention.

Nonsteroidal anti-inflammatory drug flufenamic acid is a potent activator of AMP-activated protein kinase.

PubMed

Chi, Yuan; Li, Kai; Yan, Qiaojing; Koizumi, Schuichi; Shi, Liye; Takahashi, Shuhei; Zhu, Ying; Matsue, Hiroyuki; Takeda, Masayuki; Kitamura, Masanori; Yao, Jian

2011-10-01

Flufenamic acid (FFA) is a nonsteroidal anti-inflammatory drug (NSAID). It has anti-inflammatory and antipyretic properties. In addition, it modulates multiple channel activities. The mechanisms underlying the pharmacological actions of FFA are presently unclear. Given that AMP-activated protein kinase (AMPK) has both anti-inflammatory and channel-regulating functions, we examined whether FFA induces AMPK activation. 1) Exposure of several different types of cells to FFA resulted in an elevation of AMPKα phosphorylation at Thr172. This effect of FFA was reproduced by functionally and structurally similar mefenamic acid, tolfenamic acid, niflumic acid, and meclofenamic acid. 2) FFA-induced activation of AMPK was largely abolished by the treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (an intracellular Ca(2+) chelator) or depletion of extracellular Ca(2+), whereas it was mimicked by stimulation of cells with the Ca(2+) ionophore 5-(methylamino)-2-({(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl}methyl)-1,3-benzoxazole-4-carboxylic acid (A23187) or ionomycin. 3) FFA triggered a rise in intracellular Ca(2+), which was abolished by cyclosporine, a blocker of mitochondrial permeability transition pore. Cyclosporine also abolished FFA-induced activation of AMPK. 4) Inhibition of Ca(2+)/calmodulin-dependent kinase kinase β (CaMKKβ) with 7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate (STO-609) or down-regulation of CaMKKβ with short interfering RNA largely abrogated FFA-induced activation of AMPK. 5) FFA significantly suppressed nuclear factor-κB activity and inducible nitric-oxide synthase expression triggered by interleukin-1β and tumor necrosis factor α. This suppression was also largely abrogated by STO-609. Taken together, we conclude that FFA induces AMPK activation through the Ca(2+)-CaMKKβ pathway. Activation of AMPK is a presently unrecognized important mechanism underlying the pharmacological effects of FFA.

40 CFR 180.190 - Diphenylamine; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Cattle, fat 0.01 Cattle, liver 0.1 Cattle, meat byproducts, except liver 0.01 Cattle, meat 0.01 Goat, fat 0.01 Goat, liver 0.1 Goat, meat byproducts, except liver 0.01 Goat, meat 0.01 Horse, fat 0.01 Horse, liver 0.1 Horse, meat byproducts, except liver 0.01 Horse, meat 0.01 Milk 0.01 Pear (post harvest) 5.0...

40 CFR 180.190 - Diphenylamine; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Cattle, fat 0.01 Cattle, liver 0.1 Cattle, meat byproducts, except liver 0.01 Cattle, meat 0.01 Goat, fat 0.01 Goat, liver 0.1 Goat, meat byproducts, except liver 0.01 Goat, meat 0.01 Horse, fat 0.01 Horse... Sheep, fat 0.01 Sheep, liver 0.1 Sheep, meat byproducts, except liver 0.01 Sheep, meat 0.01 (b) Section...

Effects of beta-blockers and nicardipine on oxotremorine-induced tremor in common marmosets.

PubMed

Mitsuda, M; Nomoto, M; Iwata, S

1999-10-01

Effects of beta-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as "points", which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. Beta-blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.

[Genetic aspects of pancreatic cancer].

PubMed

Grigor'eva, I N; Efimova, O V; Suvorova, T S; Tov, N L

2014-01-01

The purpose of the review--to analyze the basic data on modifiable and genetic risk factors of pancreatic cancer (PC). PC is the most fatal disease that kills about 95% of patients. Among the known risk factors for PC only for smoking, obesity, and family history a positive association with the PC risk in meta-analyzes confirmed. The PC etiology remains unclear, more than 90% of patients acquire it sporadically. Currently, the most significant genes for PC include KRAS2, p16/CDKN2, TP53, SMAD4/DPC4. Mutations in the KRAS noted in 90% of cases of pancreatic ducts adenocarcinoma. p16/CDKN2A mutation is accompanied by a 38-fold increased risk of PC compared with the general population. TP53 mutations are associated not only with carcinogenesis but also PC metastasis, as well as SMAD4/DPC4 mutations. Study of the role of genetic aspects in the PC development is necessary both to identify individuals with high PC risk, as well as for the development of gene-specific treatments, such as inhibitors of proteins, histone deacetylase, and histone acetyltransferase (vorinostat, belinostat, entinostat, panobinostat, curcumin) are in clinical trials.

Biosynthesis and NMR-studies of a double transmembrane domain from the Y4 receptor, a human GPCR.

PubMed

Zou, Chao; Naider, Fred; Zerbe, Oliver

2008-12-01

The human Y4 receptor, a class A G-protein coupled receptor (GPCR) primarily targeted by the pancreatic polypeptide (PP), is involved in a large number of physiologically important functions. This paper investigates a Y4 receptor fragment (N-TM1-TM2) comprising the N-terminal domain, the first two transmembrane (TM) helices and the first extracellular loop followed by a (His)(6) tag, and addresses synthetic problems encountered when recombinantly producing such fragments from GPCRs in Escherichia coli. Rigorous purification and usage of the optimized detergent mixture 28 mM dodecylphosphocholine (DPC)/118 mM% 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG) resulted in high quality TROSY spectra indicating protein conformational homogeneity. Almost complete assignment of the backbone, including all TM residue resonances was obtained. Data on internal backbone dynamics revealed a high secondary structure content for N-TM1-TM2. Secondary chemical shifts and sequential amide proton nuclear Overhauser effects defined the TM helices. Interestingly, the properties of the N-terminal domain of this large fragment are highly similar to those determined on the isolated N-terminal domain in the presence of DPC micelles.

[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis].

PubMed

Ishiguro, S

1999-03-01

Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.

Vaginal progesterone, but not 17α-hydroxyprogesterone caproate, has antiinflammatory effects at the murine maternal-fetal interface

PubMed Central

Furcron, Amy-Eunice; Romero, Roberto; Plazyo, Olesya; Unkel, Ronald; Xu, Yi; Hassan, Sonia S.; Chaemsaithong, Piya; Mahajan, Arushi; Gomez-Lopez, Nardhy

2016-01-01

OBJECTIVE Progestogen (vaginal progesterone or 17-alpha-hydroxyprogesterone caproate [17OHP-C]) administration to patients at risk for preterm delivery is widely used for the prevention of preterm birth (PTB). The mechanisms by which these agents prevent PTB are poorly understood. Progestogens have immunomodulatory functions; therefore, we investigated the local effects of vaginal progesterone and 17OHP-C on adaptive and innate immune cells implicated in the process of parturition. STUDY DESIGN Pregnant C57BL/6J mice received vaginal progesterone (1 mg per 200 μL, n = 10) or Replens (control, 200 μL, n = 10) from 13 to 17 days postcoitum (dpc) or were subcutaneously injected with 17OHP-C (2 mg per 100 μL, n = 10) or castor oil (control, 100 μL, n = 10) on 13, 15, and 17 dpc. Decidual and myometrial leukocytes were isolated prior to term delivery (18.5 dpc) for immunophenotyping by flow cytometry. Cervical tissues were collected to determine matrix metalloproteinase (MMP)-9 activity by in situ zymography and visualization of collagen content by Masson’s trichrome staining. Plasma concentrations of progesterone, estradiol, and cytokines (interferon [IFN]-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, and tumor necrosis factor-α) were quantified by enzyme-linked immunosorbent assays. Pregnant mice pretreated with vaginal progesterone or Replens were injected with 10 μg of an endotoxin on 16.5 dpc (n = 10 each) and monitored via infrared camera until delivery to determine the effect of vaginal progesterone on the rate of PTB. RESULTS The following results were found: (1) vaginal progesterone, but not 17OHP-C, increased the proportion of decidual CD4+ T-regulatory cells; (2) vaginal progesterone, but not 17OHP-C, decreased the proportion of decidual CD8+CD25+Foxp3+ T cells and macrophages; (3) vaginal progesterone did not cause an M1→M2 macrophage polarization but reduced the proportion of myometrial IFNγ+ neutrophils and cervical active MMP-9-positive neutrophils and monocytes; (4) 17OHP-C did not reduce the proportion of myometrial IFNy-positive neutrophils; however, it increased the abundance of cervical active MMP-9-positive neutrophils and monocytes; (5) vaginal progesterone immune effects were associated with reduced systemic concentrations of IL-1β but not with alterations in progesterone or estradiol concentrations; and (6) vaginal progesterone pretreatment protected against endotoxin-induced PTB (effect size 50%, P = .008). CONCLUSION Vaginal progesterone, but not 17OHP-C, has local antiinflammatory effects at the maternal-fetal interface and the cervix and protects against endotoxin-induced PTB. PMID:26264823

Perioperative patient safety indicators and hospital surgical volumes.

PubMed

Kitazawa, Takefumi; Matsumoto, Kunichika; Fujita, Shigeru; Yoshida, Ai; Iida, Shuhei; Nishizawa, Hirotoshi; Hasegawa, Tomonori

2014-02-28

Since the late 1990s, patient safety has been an important policy issue in developed countries. To evaluate the effectiveness of the activities of patient safety, it is necessary to quantitatively assess the incidence of adverse events by types of failure mode using tangible data. The purpose of this study is to calculate patient safety indicators (PSIs) using the Japanese Diagnosis Procedure Combination/per-diem payment system (DPC/PDPS) reimbursement data and to elucidate the relationship between perioperative PSIs and hospital surgical volume. DPC/PDPS data of the Medi-Target project managed by the All Japan Hospital Association were used. An observational study was conducted where PSIs were calculated using an algorithm proposed by the US Agency for Healthcare Research and Quality. We analyzed data of 1,383,872 patients from 188 hospitals who were discharged from January 2008 to December 2010. Among 20 provider level PSIs, four PSIs (three perioperative PSIs and decubitus ulcer) and mortality rates of postoperative patients were related to surgical volume. Low-volume hospitals (less than 33rd percentiles surgical volume per month) had higher mortality rates (5.7%, 95% confidence interval (CI), 3.9% to 7.4%) than mid- (2.9%, 95% CI, 2.6% to 3.3%) or high-volume hospitals (2.7%, 95% CI, 2.5% to 2.9%). Low-volume hospitals had more deaths among surgical inpatients with serious treatable complications (38.5%, 95% CI, 33.7% to 43.2%) than high-volume hospitals (21.4%, 95% CI, 19.0% to 23.9%). Also Low-volume hospitals had lower proportion of difficult surgeries (54.9%, 95% CI, 50.1% to 59.8%) compared with high-volume hospitals (63.4%, 95% CI, 62.3% to 64.6%). In low-volume hospitals, limited experience may have led to insufficient care for postoperative complications. We demonstrated that PSIs can be calculated using DPC/PDPS data and perioperative PSIs were related to hospital surgical volume. Further investigations focusing on identifying risk factors for poor PSIs and effective support to these hospitals are needed.

Effect of alkali metal ions on the pyrrole and pyridine π-electron systems in pyrrole-2-carboxylate and pyridine-2-carboxylate molecules: FT-IR, FT-Raman, NMR and theoretical studies

NASA Astrophysics Data System (ADS)

Świderski, G.; Wojtulewski, S.; Kalinowska, M.; Świsłocka, R.; Lewandowski, W.

2011-05-01

The FT-IR, FT-Raman and 1H and 13C NMR spectra of pyrrole-2-carboxylic acid (PCA) and lithium, sodium, potassium, rubidium and caesium pyrrole-2-carboxylates were recorded, assigned and compared in the Li → Na → K → Rb → Cs salt series. The effect of alkali metal ions on the electronic system of ligands was discussed. The obtained results were compared with previously reported ones for pyridine-2-carboxylic acid and alkali metal pyridine-2-carboxylates. Calculations for pyrrole-2-carboxylic acid and Li, Na, K pyrrole-2-carboxylates in B3LYP/6-311++G ** level and Møller-Plesset method in MP2/6-311++G ** level were made. Bond lengths, angles and dipole moments as well as aromaticity indices (HOMA, EN, GEO, I 6) for the optimized structures of pyrrole-2-carboxylic acid (PCA) and lithium, sodium, potassium pyrrole-2-carboxylates were also calculated. The degree of perturbation of the aromatic system of ligand under the influence of metals in the Li → Cs series was investigated with the use of statistical methods (linear correlation), calculated aromaticity indices and Mulliken, NBO and ChelpG population analysis method. Additionally, the Bader theory (AIM) was applied to setting the characteristic of the bond critical points what confirmed the influence of alkali metals on the pyrrole ring.

Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy.

PubMed

Lerner, Simon Fabian; Park, Ki Ho; Hubatsch, Douglas A; Erichev, Valeriy; Paczka, Jose A; Roberts, Timothy V

2017-01-01

Objective . To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods . In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results . The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (-4.6 mmHg; one-sided 95% confidence interval [-inf, -3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion . Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391.

Novel Three-Component Phenazine-1-Carboxylic Acid 1,2-Dioxygenase in Sphingomonas wittichii DP58

PubMed Central

Zhao, Qiang; Wang, Wei; Huang, Xian-Qing; Zhang, Xue-Hong

2017-01-01

ABSTRACT Phenazine-1-carboxylic acid, the main component of shenqinmycin, is widely used in southern China for the prevention of rice sheath blight. However, the fate of phenazine-1-carboxylic acid in soil remains uncertain. Sphingomonas wittichii DP58 can use phenazine-1-carboxylic acid as its sole carbon and nitrogen sources for growth. In this study, dioxygenase-encoding genes, pcaA1A2, were found using transcriptome analysis to be highly upregulated upon phenazine-1-carboxylic acid biodegradation. PcaA1 shares 68% amino acid sequence identity with the large oxygenase subunit of anthranilate 1,2-dioxygenase from Rhodococcus maanshanensis DSM 44675. The dioxygenase was coexpressed in Escherichia coli with its adjacent reductase-encoding gene, pcaA3, and ferredoxin-encoding gene, pcaA4, and showed phenazine-1-carboxylic acid consumption. The dioxygenase-, ferredoxin-, and reductase-encoding genes were expressed in Pseudomonas putida KT2440 or E. coli BL21, and the three recombinant proteins were purified. A phenazine-1-carboxylic acid conversion capability occurred in vitro only when all three components were present. However, P. putida KT2440 transformed with pcaA1A2 obtained phenazine-1-carboxylic acid degradation ability, suggesting that phenazine-1-carboxylic acid 1,2-dioxygenase has low specificities for its ferredoxin and reductase. This was verified by replacing PcaA3 with RedA2 in the in vitro enzyme assay. High-performance liquid chromatography–mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) analysis showed that phenazine-1-carboxylic acid was converted to 1,2-dihydroxyphenazine through decarboxylation and hydroxylation, indicating that PcaA1A2A3A4 constitutes the initial phenazine-1-carboxylic acid 1,2-dioxygenase. This study fills a gap in our understanding of the biodegradation of phenazine-1-carboxylic acid and illustrates a new dioxygenase for decarboxylation. IMPORTANCE Phenazine-1-carboxylic acid is widely used in southern China as a key fungicide to prevent rice sheath blight. However, the degradation characteristics of phenazine-1-carboxylic acid and the environmental consequences of the long-term application are not clear. S. wittichii DP58 can use phenazine-1-carboxylic acid as its sole carbon and nitrogen sources. In this study, a three-component dioxygenase, PcaA1A2A3A4, was determined to be the initial dioxygenase for phenazine-1-carboxylic acid degradation in S. wittichii DP58. Phenazine-1-carboxylic acid was converted to 1,2-dihydroxyphenazine through decarboxylation and hydroxylation. This finding may help us discover the pathway for phenazine-1-carboxylic acid degradation. PMID:28188209

Increased gluconeogenesis in rats exposed to hyper-G stress

NASA Technical Reports Server (NTRS)

Daligcon, B. C.; Oyama, J.; Hannak, K.

1985-01-01

The effect of gluconeogenesis on the levels of plasma glucose and liver glycogen was studied in rats exposed to hyper-G stress. Incorporation of lactate, alanine, or glycerol, labeled with C-14, into plasma glucose and liver glycogen was measured in rats centrifuged at 3.1 G for 0.25, 0.50, and 1.0-hr periods, and was compared to noncentrifuged controls injected with appropriate glycogen precursors. It was found that exposure to G-stress leads to increased incorporation from all three substrates into both plasma glucose and liver glycogen. These early incorporation increases were blocked upon pre-G administration of 5-methoxyindole-2-carboxylic acid, a gluconeogenesis inhibitor, or propanolol, a beta-adrenergic blocker, as well as by adrenodemedullation. Results indicate that the rapid rise in plasma glucose, as well as in liver glycogen in rats exposed to hyper-G stress is due to an increased rate of gluconeogenesis, and that epinephrine, released in response to hyper-G-induced activation of the sympathetic-adrenal system, plays a dominant role during the early stages of hyper-G stress.

Hemodynamic effects of renin-angiotensin-aldosterone inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for portal hypertension in cirrhosis: A meta-analysis

PubMed Central

Wang, Jianrong; Lu, Wenxia; Li, Jingjing; Zhang, Rong; Zhou, Yuqing; Yin, Qin; Zheng, Yuanyuan; Wang, Fan; Xia, Yujing; Chen, Kan; Li, Sainan; Liu, Tong; Lu, Jie; Zhou, Yingqun; Guo, Chuan-Yong

2017-01-01

β-blockers are commonly used for the treatment of acute variceal bleeding in cirrhosis. Renin-angiotensin-aldosterone antagonists (angiotensin I-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists) are potential therapies for portal hypertension. Several studies have compared the renin-angiotensin-aldosterone system (RAAS) inhibitor and β-blocker combination therapy vs. β-blocker monotherapy, with inconsistent results. The aim of the present study was to assess the efficacy of the RAAS inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for hepatic vein pressure gradient (HVPG) reduction in cirrhosis. Studies were obtained using PubMed, Embase, Medline and Cochrane library databases up to July 2015, and the weighted mean difference (WMD) in HVPG reduction was used as a measure of treatment efficacy. In total, three studies (91 patients) were included. When compared to the β-blocker monotherapy, the RAAS inhibitor and β-blocker combination therapy resulted in a significant HVPG reduction [WMD 1.70; 95% confidence interval (CI): 0.52–2.88]. However, there was no significant difference in the heart rate reduction between the monotherapy and combination therapy groups (WMD −0.11; 95% CI: −3.51–3.29). In addition, no significant difference in the hemodynamic response was observed between the two groups (WMD 1.46; 95% CI: 0.93–2.30). In conclusion, the RAAS inhibitor and β-blocker combination therapy reduces portal hypertension significantly and to a greater extent than β-blocker monotherapy. Both therapies reduced the heart rate to similar levels; however, the RAAS inhibitor and β-blocker combination therapy reduced the mean arterial pressure to a greater extent. Due to the limited number of studies included, the data available do not allow a satisfactory comparison of adverse events. Moreover, further larger-scale trials are required in order to strengthen the results of the present study. PMID:28565796

Gestational dietary protein is associated with sex specific decrease in blood flow, fetal heart growth and post-natal blood pressure of progeny.

PubMed

Hernandez-Medrano, Juan H; Copping, Katrina J; Hoare, Andrew; Wapanaar, Wendela; Grivell, Rosalie; Kuchel, Tim; Miguel-Pacheco, Giuliana; McMillen, I Caroline; Rodgers, Raymond J; Perry, Viv E A

2015-01-01

The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14 mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60 d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98 dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36 dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60 d up to 23 dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system.

Hair growth-promoting effect of Aconiti Ciliare Tuber extract mediated by the activation of Wnt/β-catenin signaling.

PubMed

Park, Phil-June; Moon, Byoung-San; Lee, Soung-Hoon; Kim, Su-Na; Kim, Ah-Reum; Kim, Hyung-Jun; Park, Won-Seok; Choi, Kang-Yell; Cho, Eun-Gyung; Lee, Tae Ryong

2012-11-02

The activation of Wnt/β-catenin signaling pathway plays an important role in hair follicle morphogenesis by stimulating bulge stem cells. This study was to obtain the activator of Wnt/β-catenin signaling pathway from natural products and to determine whether this activator can induce anagen hair growth in mice. To identify materials that activate Wnt/β-catenin signaling pathway, 800 natural product extracts were screened using pTOPFlash assay and neural progenitor cell (NPC) differentiation assay. A selected extract was further tested for its effects on alkaline phosphatase (ALP) activity in human immortalized dermal papilla cell (iDPC) and the proliferation in iDPC and immortalized rat vibrissa DPC (RvDP). Finally, hair growth-promoting effects were evaluated in the dorsal skin of C57BL/6 mice. Aconiti Ciliare Tuber (ACT) extract was one of the most active materials in both pTOPFlash and NPC differentiation assays. It promoted the differentiation of NPC cells even under proliferation-stimulating conditions (basic fibroblast growth factor: bFGF). It also increased ALP activity and proliferation of iDPC in dose-dependent manners, and it stimulated the induction of the anagen hair growth in C57BL/6 mice. These results suggest that ACT extract activates the Wnt/β-catenin signaling pathway by enhancing β-catenin transcription and has the potential to promote the induction of hair growth via activation of the stem cell activity of the dermal papilla cells. This is the first report indicating benefits of ACT extract in hair loss prevention by triggering the activation of Wnt/β-catenin signaling pathway and induction of the anagen hair growth in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Delayed Ileal Pouch Anal Anastomosis Has a Lower 30-Day Adverse Event Rate: Analysis From the National Surgical Quality Improvement Program.

PubMed

Kochar, Bharati; Barnes, Edward L; Peery, Anne F; Cools, Katherine S; Galanko, Joseph; Koruda, Mark; Herfarth, Hans H

2018-04-25

Ulcerative colitis (UC) patients requiring colectomy often have a staged ileal pouch anal anastomosis (IPAA). There are no prospective data comparing timing of pouch creation. We aimed to compare 30-day adverse event rates for pouch creation at the time of colectomy (PTC) with delayed pouch creation (DPC). Using prospectively collected data from 2011-2015 through the National Surgical Quality Improvement Program, we conducted a cohort study including subjects aged ≥18 years with a postoperative diagnosis of UC. We assessed 30-day postoperative rates of unplanned readmissions, reoperations, and major and minor adverse events (AEs), comparing the stage of the surgery where the pouch creation took place. Using a modified Poisson regression model, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) adjusting for age, sex, race, body mass index, smoking status, diabetes, albumin, and comorbidities. Of 2390 IPAA procedures, 1571 were PTC and 819 were DPC. In the PTC group, 51% were on chronic immunosuppression preoperatively, compared with 15% in the DPC group (P < 0.01). After controlling for confounders, patients who had DPC were significantly less likely to have unplanned reoperations (RR, 0.42; 95% CI, 0.24-0.75), major AEs (RR, 0.72; 95% CI, 0.52-0.99), and minor AEs (RR, 0.48; 95% CI, 0.32-0.73) than PTC. Patients undergoing delayed pouch creation were at lower risk for unplanned reoperations and major and minor adverse events compared with patients undergoing pouch creation at the time of colectomy. 10.1093/ibd/izy082_video1izy082.video15776112442001.

Molecular docking, TG/DTA, molecular structure, harmonic vibrational frequencies, natural bond orbital and TD-DFT analysis of diphenyl carbonate by DFT approach

NASA Astrophysics Data System (ADS)

Xavier, S.; Periandy, S.; Carthigayan, K.; Sebastian, S.

2016-12-01

Vibrational spectral analysis of Diphenyl Carbonate (DPC) is carried out by using FT-IR and FT-Raman spectroscopic techniques. It is found that all vibrational modes are in the expected region. Gaussian computational calculations were performed using B3LYP method with 6-311++G (d, p) basis set. The computed geometric parameters are in good agreement with XRD data. The observation shows that the structure of the carbonate group is unsymmetrical by ∼5° due to the attachment of the two phenyl rings. The stability of the molecule arising from hyperconjugative interaction and charge delocalization are analyzed by Natural Bond Orbital (NBO) study and the results show the lone pair transition has higher stabilization energy compared to all other. The 1H and 13C NMR chemical shifts are calculated using the Gauge-Including Atomic Orbital (GIAO) method with B3LYP/6-311++G (d, p) method. The chemical shifts computed theoretically go very closer to the experimental results. A study on the electronic and optical properties; absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies and Molecular electrostatic potential (MEP) exhibit the high reactivity nature of the molecule. The non-linear optical property of the DPC molecule predicted theoretically found to be good candidate for NLO material. TG/DTA analysis was made and decomposition of the molecule with respect to the temperature was studied. DPC having the anthelmintic activity is docked in the Hemoglobin of Fasciola hepatica protein. The DPC has been screened to antimicrobial activity and found to exhibit antibacterial effects.

Crystal structure of 3-amino-pyridinium 1'-carb-oxy-ferrocene-1-carboxyl-ate.

PubMed

Medved'ko, Aleksei V; Churakov, Andrei V; Yu, Haojie; Li, Wang; Vatsadze, Sergey Z

2017-06-01

The structure of the title salt, (C 5 H 7 N 2 )[Fe(C 6 H 4 O 2 )(C 6 H 5 O 2 )], consists of 3-amino-pyridinium cations and 1'-carb-oxy-ferrocene-1-carboxyl-ate monoanions. The ferrocenyl moiety of the anion adopts a typical sandwich structure, with Fe-C distances in the range 2.0270 (15)-2.0568 (17) Å. The anion possesses an eclipsed conformation, with the torsion angle φ (C subst -Cp cent -Cp cent - C subst ) equal to 66.0°. The conformations of other 1'-carb-oxy-ferrocene-1-carboxyl-ate monoanions are compared and analyzed on the basis of literature data.

A Novel Small Molecule Modulator of Amyloid Pathology.

PubMed

Lovell, Mark A; Lynn, Bert C; Fister, Shuling; Bradley-Whitman, Melissa; Murphy, M Paul; Beckett, Tina L; Norris, Christopher M

2016-05-04

Because traditional approaches to drug development for Alzheimer's disease are becoming increasingly expensive and in many cases disappointingly unsuccessful, alternative approaches are required to shift the paradigm. Following leads from investigations of dihydropyridine calcium channel blockers, we observed unique properties from a class of functionalized naphthyridines and sought to develop these as novel therapeutics that minimize amyloid pathology without the adverse effects associated with current therapeutics. Our data show methyl 2,4-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridine-1-carboxylate (BNC-1) significantly decreases amyloid burden in a well-established mouse model of amyloid pathology through a unique mechanism mediated by Elk-1, a transcriptional repressor of presenilin-1. Additionally, BNC-1 treatment leads to increased levels of synaptophysin and synapsin, markers of synaptic integrity, but does not adversely impact presenilin-2 or processing of Notch-1, thus avoiding negative off target effects associated with pan-gamma secretase inhibition. Overall, our data show BNC-1 significantly decreases amyloid burden and improves markers of synaptic integrity in a well-established mouse model of amyloid deposition by promoting phosphorylation and activation of Elk-1, a transcriptional repressor of presenilin-1 but not presenilin-2. These data suggest BNC-1 might be a novel, disease-modifying therapeutic that will alter the pathogenesis of Alzheimer's disease.

Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients.

PubMed

Ogawa, Hisao; Kim-Mitsuyama, Shokei; Matsui, Kunihiko; Jinnouchi, Tomio; Jinnouchi, Hideaki; Arakawa, Kikuo

2012-10-01

It is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk. The objective of the study was to compare the efficacy of these treatments in elderly, high-risk Japanese hypertensive patients. The OlmeSartan and Calcium Antagonists Randomized (OSCAR) study was a multicenter, prospective, randomized, open-label, blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease. Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were randomly assigned to receive 40 mg/d olmesartan (high-dose angiotensin II receptor blocker) or a calcium channel blocker + 20 mg/d olmesartan (angiotensin II receptor blocker + calcium channel blocker). The primary end point was a composite of cardiovascular events and noncardiovascular death. During a 3-year follow-up, blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group. Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group. More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group (58 vs 48 events, hazard ratio [HR], 1.31, 95% confidence interval, 0.89-1.92; P=.17). In patients with cardiovascular disease at baseline, more primary events occurred in the high-dose angiotensin II receptor blocker group (HR, 1.63, P=.03); in contrast, fewer events were observed in the subgroup without cardiovascular disease (HR, 0.52, P=.14). This treatment-by-subgroup interaction was significant (P=.02). The angiotensin II receptor blocker and calcium channel blocker combination lowered blood pressure more than the high-dose angiotensin II receptor blocker and reduced the incidence of primary end points more than the high-dose angiotensin II receptor blocker in patients with cardiovascular disease. The addition of a second antihypertensive agent is more effective at lowering blood pressure than simply doubling the dose of an existing agent. Copyright © 2012 Elsevier Inc. All rights reserved.

RESCUE - Reduction of MRI SNR Degradation by Using an MR-Synchronous Low-Interference PET Acquisition Technique

NASA Astrophysics Data System (ADS)

Gebhardt, Pierre; Wehner, Jakob; Weissler, Bjoern; Frach, Thomas; Marsden, Paul K.; Schulz, Volkmar

2015-06-01

Devices aiming at combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) to enable simultaneous PET/MR image acquisition have to fulfill demanding requirements to avoid mutual magneticas well as electromagnetic-field-related interferences which lead to image quality degradation. Particularly Radio-Frequency (RF)-field-related interferences between PET and MRI may lead to MRI SNR reduction, thereby deteriorating MR image quality. RF shielding of PET electronics is therefore commonly applied to reduce RF emission and lower the potential coupling into MRI RF coil(s). However, shields introduce eddy-current-induced MRI field distortions and should thus be minimized or ideally omitted. Although the MRI noise floor increase caused by a PET system might be acceptable for many MRI applications, some MRI protocols, such as fast or high-resolution MRI scans, typically suffer from low SNR and might need more attention regarding RF silence to preserve the intrinsic MRI SNR. For such cases, we propose RESCUE, an MRI-synchronously-gated PET data acquisition technique: By interrupting the PET acquisition during MR signal receive phases, PET-related RF emission may be minimized, leading to MRI SNR preservation. Our PET insert Hyperion IID using Philips Digital Photon Counting (DPC) sensors serves as the platform to demonstrate RESCUE. To make the DPC sensor suitable for RESCUE to be applied for many MRI sequences with acquisition time windows in the range of a few milliseconds, we present in this paper a new technique which enables rapid DPC sensor operation interruption by dramatically lowering the overhead time to interrupt and restart the sensor operation. Procedures to enter and leave gated PET data acquisition may imply sensitivity losses which add to the ones occurring during MRI RF acquisition. For the case of our PET insert, the new DPC quick-interruption technique yields a PET sensitivity loss reduction by a factor of 78 when compared to the loss introduced with the standard start/stop procedure. For instance, PET sensitivity losses related to overhead time are 2.9% in addition to the loss related to PET gating being equal to the MRI RF acquisition duty cycle (14.7%) for an exemplary T1-weighted 3D-FFE MRI sequence. MRI SNR measurement results obtained with one Singles Detection Module (SDM) using no RF shield demonstrate a noise floor reduction by a factor of 2.1, getting close to the noise floor level of the SNR reference scan (SDM off-powered) when RESCUE was active.

Data Processing Center of Radioastron Project: 3 years of operation.

NASA Astrophysics Data System (ADS)

Shatskaya, Marina

ASC DATA PROCESSING CENTER (DPC) of Radioastron Project is a fail-safe complex centralized system of interconnected software/ hardware components along with organizational procedures. Tasks facing of the scientific data processing center are organization of service information exchange, collection of scientific data, storage of all of scientific data, data science oriented processing. DPC takes part in the informational exchange with two tracking stations in Pushchino (Russia) and Green Bank (USA), about 30 ground telescopes, ballistic center, tracking headquarters and session scheduling center. Enormous flows of information go to Astro Space Center. For the inquiring of enormous data volumes we develop specialized network infrastructure, Internet channels and storage. The computer complex has been designed at the Astro Space Center (ASC) of Lebedev Physical Institute and includes: - 800 TB on-line storage, - 2000 TB hard drive archive, - backup system on magnetic tapes (2000 TB); - 24 TB redundant storage at Pushchino Radio Astronomy Observatory; - Web and FTP servers, - DPC management and data transmission networks. The structure and functions of ASC Data Processing Center are fully adequate to the data processing requirements of the Radioastron Mission and has been successfully confirmed during Fringe Search, Early Science Program and first year of Key Science Program.

Direct pulp capping in primary molars using a resin-modified Portland cement-based material (TheraCal) compared to MTA with 12-month follow-up: a randomised clinical trial.

PubMed

Erfanparast, L; Iranparvar, P; Vafaei, A

2018-05-16

This study was to compare the success of resin-modified Portland cement-based material (TheraCal) with MTA in direct pulp capping (DPC) of primary molars. Symmetrical bilateral primary molars (92) from 46 healthy subjects aged 5-7 years were included in this split-mouth randomised clinical trial. DPC for small non-contaminated pulp exposures using either TheraCal or MTA were randomly performed in symmetrical molars. Thereafter, teeth were restored with amalgam. Clinical and radiographic evaluations were performed at 6 and 12 month follow-ups. Data were analysed using Chi square test at a significance level of 0.05. At the final follow-up session 74 teeth were available. After 12 months, the overall success rates for MTA and TheraCal were 94.5 and 91.8%, respectively. The difference between outcomes of the two groups was not statistically significant (P > 0.05). Within the limitations of the current study, radiographic and clinical findings revealed that TheraCal exhibited a comparable outcome to MTA in DPC of primary molars after 12 months.

Functional mapping of hospitals by diagnosis-dominant case-mix analysis.

PubMed

Fushimi, Kiyohide; Hashimoto, Hideki; Imanaka, Yuichi; Kuwabara, Kazuaki; Horiguchi, Hiromasa; Ishikawa, Kohichi B; Matsuda, Shinya

2007-04-10

Principles and methods for the allocation of healthcare resources among healthcare providers have long been health policy research issues in many countries. Healthcare reforms including the development of a new case-mix system, Diagnosis Procedure Combination (DPC), and the introduction of a DPC-based payment system are currently underway in Japan, and a methodology for adequately assessing the functions of healthcare providers is needed to determine healthcare resource allocations. By two-dimensional mapping of the rarity and complexity of diagnoses for patients receiving treatment, we were able to quantitatively demonstrate differences in the functions of different healthcare service provider groups. On average, inpatients had diseases that were 3.6-times rarer than those seen in outpatients, while major teaching hospitals treated inpatients with diseases 3.0-times rarer on average than those seen at small hospitals. We created and evaluated a new indicator for DPC, the diagnosis-dominant case-mix system developed in Japan, whereby the system was used to assess the functions of healthcare service providers. The results suggest that it is possible to apply the case-mix system to the integrated evaluation of outpatient and inpatient healthcare services and to the appropriate allocation of healthcare resources among health service providers.

Efficacy of beta-blocker therapy in symptomatic athletes with exercise-induced intra-ventricular gradients

PubMed Central

2010-01-01

Background Upright exercise stress echocardiography (SE) induces significant intraventricular gradient (IVG) and systolic anterior motion (SAM) in a large proportion of symptomatic athletes, who may therefore benefit from a negative inotropic therapy. The purpose of the present study was to assess the effect of chronic oral β blocker therapy on the occurrence of exercise-induced IVG and mitral valve SAM, in symptomatic athletes. Methods We enrolled 35 symptomatic athletes (age = 23 ± 11 years) with IVG (>30 mmHg) during SE off therapy. All repeated SE on chronic oral beta-blocker therapy (atenolol up to 50 mg, bisoprolol up to 10 mg, or metoprolol up to 100 mg daily according to physician-driven choice). Results On therapy, there was during SE a reduction in IVG (35 off vs 17 on beta blocker, p < 0.01), decrease of IVG (102 ± 34 mmHg off vs 69 ± 24 mmHg on beta blocker, p < 0.01), peak heart rate (178 ± 15 bpm off vs 157 ± 9 bpm on beta blocker), SAM (24 off vs 9 on beta blocker, p < 0.001), symptoms during SE (17 off vs 2 on beta blocker p < 0.001), ST segment depression (13 off vs 2 on beta blocker, p < 0.001). Conclusions In athletes with positive screening on medical evaluation for sports practice and IVG on exertion, treatment with oral beta blockers improved symptoms in the large majority of patients. Symptomatic benefit was mirrored by objective evidence of improvement of echocardiographic signs of obstruction (IVG and SAM) and reduction of ischemia-like electrocardiographic changes. PMID:20813061

Isolation of proflavine as a blocker of G protein-gated inward rectifier potassium channels by a cell growth-based screening system.

PubMed

Kawada, Hitoshi; Inanobe, Atsushi; Kurachi, Yoshihisa

2016-10-01

The overexpression of Kir3.2, a subunit of the G protein-gated inwardly rectifying K(+) channel, is implicated in some of the neurological phenotypes of Down syndrome (DS). Chemical compounds that block Kir3.2 are expected to improve the symptoms of DS. The purpose of this study is to develop a cell-based screening system to identify Kir3.2 blockers and then investigate the mode of action of the blocker. Chemical screening was carried out using a K(+) transporter-deficient yeast strain that expressed a constitutively active Kir3.2 mutant. The mode of action of an effective blocker was electrophysiologically analyzed using Kir channels expressed in Xenopus oocytes. Proflavine was identified to inhibit the growth of Kir3.2-transformant cells and Kir3.2 activity in a concentration-dependent manner. The current inhibition was strong when membrane potentials (Vm) was above equilibrium potential of K(+) (EK). When Vm was below EK, the blockage apparently depended on the difference between Vm and [K(+)]. Furthermore, the inhibition became stronger by lowering extracellular [K(+)]. These results indicated that the yeast strain serves as a screening system to isolate Kir3.2 blockers and proflavine is a prototype of a pore blocker of Kir3.2. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling the Effects of β1-Adrenergic Receptor Blockers and Polymorphisms on Cardiac Myocyte Ca2+ Handling

PubMed Central

Amanfu, Robert K.

2014-01-01

β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on cardiac physiology. While some studies indicate that β-blockers are efficacious by inhibiting β-adrenergic signaling, other studies suggest that they work by maintaining β-adrenergic responsiveness. Here, we use a systems pharmacology approach to test the hypothesis that in ventricular myocytes, these two apparently conflicting mechanisms for β-blocker efficacy can occur concurrently. We extended a computational model of the β1-adrenergic pathway and excitation-contraction coupling to include detailed receptor interactions for 19 ligands. Model predictions, validated with Ca2+ and Förster resonance energy transfer imaging of adult rat ventricular myocytes, surprisingly suggest that β-blockers can both inhibit and maintain signaling depending on the magnitude of receptor stimulation. The balance of inhibition and maintenance of β1-adrenergic signaling is predicted to depend on the specific β-blocker (with greater responsiveness for metoprolol than carvedilol) and β1-adrenergic receptor Arg389Gly polymorphisms. PMID:24867460

Rescue of a duck circovirus from an infectious DNA clone in ducklings.

PubMed

Li, Pengfei; Zhang, Zhilong; Jia, Renyong; Mao, Sai; Wang, Mingshu; Jia, Ruiling; Liu, Mafeng; Zhu, Dekang; Chen, Shun; Sun, Kunfeng; Yin, Zhongqiong; Chen, Xiaoyue; Cheng, Anchun

2015-05-30

Duck circovirus may predispose the host to immunosuppression and may serve as an immunological trigger for further complicated disease progression. Due to the lack of a cell culture system for propagating DuCV, little is known regarding the molecular biology and pathogenesis of DuCV. The aim of this study was to describe the construction and initial in vivo characterization of full-length DNA clones of DuCV (pIC-Mu2DuCV) and its infectivity under in vivo conditions. The constructed pIC-Mu2DuCV contained two copies of the whole DuCV genome and an introduced Xho I restriction enzyme site. Eighty-one 10-day-old conventional ducklings that were free of DuCV were randomly divided equally into three groups (1, 2 and 3). The ducklings in groups 1, 2 and 3 were inoculated intramuscularly with pIC-Mu2DuCV, wild-type virus GH01 and PBS, respectively. Subsequently, all of the ducklings were examined clinically, which were each given a physical condition score, and their rectal temperatures were taken daily during the experimental period. DuCV genomes in serum samples and in various tissues from all of the ducklings at 0, 1, 3, 5, 7, 10, 15, 21 and 28 DPC were detected by PCR and real-time quantitative PCR, respectively. The average daily weight gain (ADWG) of group 3 was significantly higher than those of groups 1 and 2, and the temperature of all ducklings was stable between 41.7 °C and 42.2 °C. The clinical values (physical condition scores) of groups 1, 2 and 3 were 12.5, 15.6 and 0, respectively. In addition, viremia occurred at 15 and 10 days post-challenge (DPC) in groups 1 and 2, and antibodies could be detected in these ducklings at 21 and 15 DPC. Proliferation ability analysis showed that the viral titers of group 1 were lower than those of their parental viruses in group 2. This study shows that the rescued viruses are not significantly different but exhibit lower pathogenicity and proliferation ability compared with the parental virus. The results will facilitate future studies on DuCV pathogenesis and biology.

Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker

PubMed Central

Ta, Chau M; Adomaviciene, Aiste; Rorsman, Nils J G; Garnett, Hannah

2016-01-01

Background and Purpose Calcium‐activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene‐9‐carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined. Experimental Approach Patch‐clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels. Key Results In the presence of high intracellular Ca2+, A9C inhibited TMEM16A currents in a voltage‐dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca2+ concentrations, was also voltage‐dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open‐channel block mechanism. Activation was due to a dramatic leftward shift in the steady‐state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl−, suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects. Conclusions and Implications A9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels. PMID:26562072

Major barriers against renin-angiotensin-aldosterone system blocker use in chronic kidney disease stages 3-5 in clinical practice: a safety concern?

PubMed

Yildirim, Tolga; Arici, Mustafa; Piskinpasa, Serhan; Aybal-Kutlugun, Aysun; Yilmaz, Rahmi; Altun, Bulent; Erdem, Yunus; Turgan, Cetin

2012-01-01

Renin-angiotensin-aldosterone system (RAAS) blockers are underutilized in patients with chronic kidney disease (CKD). We aimed to determine barriers against the use of RAAS blockers in these patients. Patients with stage 3-5 CKD referred to Hacettepe University Hospital Nephrology Unit during a 1 year period were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166 male, 113 female) were analyzed. The mean age of the patients was 56.7 ± 15.2 years, mean serum creatinine was 2.45 ± 1.44 mg/dL, and mean glomerular filtration rate was 33.3 ± 15.1 mL/min. The mean follow-up time was 22.0 ± 21.9 months and the clinical visit number was 4.0 ± 3.5. Angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of patients, RAAS blockers had either been used earlier or were being used. Hyperkalemia was the principal reason for both not starting and also discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for not starting RAAS blockers were unclear. This study showed that hyperkalemia is the major barrier against the use of RAAS blockers in patients with CKD. There was, however, a subset of patients who did not receive RAAS blockers even without clear contraindications.

40 CFR 180.426 - 2-[4,5-Dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinoline carboxylic acid...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinoline carboxylic acid; tolerance for residues. 180.426 Section 180...-Dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinoline carboxylic acid; tolerance for...)-5-oxo-1H-imidazol-2-yl]-3-quinoline carboxylic acid, in or on the raw agricultural commodity soybean...

Periodontal regeneration with nano-hyroxyapatite-coated silk scaffolds in dogs

PubMed Central

Yang, Cheryl; Lee, Jung-Seok; Jung, Ui-Won; Seo, Young-Kwon; Park, Jung-Keug

2013-01-01

Purpose In this study, we investigated the effect of silk scaffolds on one-wall periodontal intrabony defects. We conjugated nano-hydroxyapatite (nHA) onto a silk scaffold and then seeded periodontal ligament cells (PDLCs) or dental pulp cells (DPCs) onto the scaffold. Methods Five dogs were used in this study. Bilateral 4 mm×2 mm (depth×mesiodistal width), one-wall intrabony periodontal defects were surgically created on the distal side of the mandibular second premolar and the mesial side of the mandibular fourth premolar. In each dog, four of the defects were separately and randomly assigned to the following groups: the PDLC-cultured scaffold transplantation group (PDLC group), the DPC-cultured scaffold transplantation group (DPC group), the normal saline-soaked scaffold transplantation group, and the control group. The animals were euthanized following an 8-week healing interval for clinical, scanning electron microscopy (SEM), and histologic evaluations. Results There was no sign of inflammation or other clinical signs of postoperative complications. The examination of cell-seeded constructs by SEM provided visual confirmation of the favorable characteristics of nHA-coated silk scaffolds for tissue engineering. The scaffolds exhibited a firm connective porous structure in cross section, and after PDLCs and DPCs were seeded onto the scaffolds and cultured for 3 weeks, the attachment of well-spread cells and the formation of extracellular matrix (ECM) were observed. The histologic analysis revealed that a well-maintained grafted volume was present at all experimental sites for 8 weeks. Small amounts of inflammatory cells were seen within the scaffolds. The PDLC and DPC groups did not have remarkably different histologic appearances. Conclusions These observations indicate that nHA-coated silk scaffolds can be considered to be potentially useful biomaterials for periodontal regeneration. PMID:24455445

Induced Wnt5a expression perturbs embryonic outgrowth and intestinal elongation, but is well-tolerated in adult mice.

PubMed

Bakker, Elvira R M; Raghoebir, Lalini; Franken, Patrick F; Helvensteijn, Werner; van Gurp, Léon; Meijlink, Frits; van der Valk, Martin A; Rottier, Robbert J; Kuipers, Ernst J; van Veelen, Wendy; Smits, Ron

2012-09-01

Wnt5a is essential during embryonic development, as indicated by mouse Wnt5a knockout embryos displaying outgrowth defects of multiple structures including the gut. The dynamics of Wnt5a involvement in these processes is unclear, and perinatal lethality of Wnt5a knockout embryos has hampered investigation of Wnt5a during postnatal stages in vivo. Although in vitro studies have suggested a relevant role for Wnt5a postnatally, solid evidence for a significant impact of Wnt5a within the complexity of an adult organism is lacking. We generated a tightly-regulated inducible Wnt5a transgenic mouse model and investigated the effects of Wnt5a induction during different time-frames of embryonic development and in adult mice, focusing on the gastrointestinal tract. When induced in embryos from 10.5 dpc onwards, Wnt5a expression led to severe outgrowth defects affecting the gastrointestinal tracts, limbs, facial structures and tails, closely resembling the defects observed in Wnt5a knockout mice. However, Wnt5a induction from 13.5 dpc onwards did not cause this phenotype, indicating that the most critical period for Wnt5a in embryonic development is prior to 13.5 dpc. In adult mice, induced Wnt5a expression did not reveal abnormalities, providing the first in vivo evidence that Wnt5a has no major impact on mouse intestinal homeostasis postnatally. Protein expression of Wnt5a receptor Ror2 was strongly reduced in adult intestine compared to embryonic stages. Moreover, we uncovered a regulatory process where induction of Wnt5a causes downregulation of its receptor Ror2. Taken together, our results indicate a role for Wnt5a during a restricted time-frame of embryonic development, but suggest no impact during homeostatic postnatal stages. Copyright © 2012 Elsevier Inc. All rights reserved.

Study of long term structural and functional changes in medically controlled glaucoma

PubMed Central

Pandey, Achyut N; Sujata, S

2014-01-01

AIM Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. METHODS Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. RESULTS A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. CONCLUSION Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide. PMID:24634878

Study of long term structural and functional changes in medically controlled glaucoma.

PubMed

Pandey, Achyut N; Sujata, S

2014-01-01

Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide.

Evaluation of skin permeation of β-blockers for topical drug delivery.

PubMed

Chantasart, Doungdaw; Hao, Jinsong; Li, S Kevin

2013-03-01

β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. The present results suggest the possibility of topical treatment of hemangioma using β-blockers.

Numerical Study on Recombination Efficiency at 4,4'-Bis(2,2'-diphenylvinyl)-1,1'-spirobiphenyl/Tris(8-quinolinolato)aluminium Interface in Organic Light Emitting Diodes

NASA Astrophysics Data System (ADS)

Hwang, Young Wook; Kim, Kwang Sik; Won, Tae Young

2013-10-01

In this paper, we report our numerical study on the electrical and optical properties of the organic light emitting diodes (OLEDs) devices with n-doped layer, which is inserted for the purpose of reducing the interface barrier height between the cathode and the electron transport layer (ETL). We performed finite element method (FEM) simulation on OLEDs in order to understand the transport behavior of carriers, recombination kinetics, and emission property. Our model includes Poisson's equation, continuity equation to account for behavior of electrons and holes and exciton continuity/transfer equation to account for recombination of carriers. We employ the multilayer structure which consists of indium tin oxide (ITO); 2,2',7,7'-tetrakis(N,N-diphenylamine)-9,9'-spirobi-fluorene (S-TAD); 4,4'-bis(2,2'-diphenylvinyl)-1,1'-spirobiphenyl (S-DPVBi); tris(8-quinolinolato)aluminium (Alq3); calcium (Ca).

Efficacy of Calcium Channel Blockers on Major Cardiovascular Outcomes for the Treatment of Hypertension in Asian Populations: A Meta-analysis.

PubMed

Tran, Karen C; Leung, Alexander A; Tang, Karen L; Quan, Hude; Khan, Nadia A

2017-05-01

Whether calcium channel blockers exert a greater effect on cardiovascular risk reduction in Asian populations than other antihypertensive agents is unclear. We conducted a meta-analysis of hypertension trials of dihydropyridine calcium channel blockers in Asian populations to clarify this association. EMBASE, MEDLINE, and Cochrane databases were searched (from inception to August 2016) for randomized controlled trials on cardiovascular death, major adverse cardiovascular events, stroke, congestive heart failure, and coronary revascularization in Asian persons with hypertension. We identified 9 trials that reported data specific to Asian populations (N = 29,643). These trials included 1 placebo-controlled trial and 8 active comparator trials; of these, 5 had angiotensin receptor blockers as the active comparator. One placebo-controlled trial (n = 9711) showed significantly reduced cardiovascular mortality, major adverse cardiovascular events, and stroke with calcium channel blockers. Among 8 active comparator trials (n = 19,932), there were no significant differences in mortality (relative risk [RR], 1.10; 95% confidence interval [CI], 0.72-1.67; I 2  = 0.0%), major adverse cardiovascular events (RR, 1.02; 95% CI, 0.90-1.15; I 2  = 0.0%), stroke (RR, 0.97; 95% CI, 0.80-1.17; I 2  = 0.0%), congestive heart failure (RR, 1.01; 95% CI, 0.51-2.00; I 2  = 53.7), or coronary revascularization rates (RR, 0.98; 95% CI, 0.76-1.25; I 2  = 0.0%) in the calcium channel blocker group compared with other antihypertensive agents. When restricting the meta-analysis to angiotensin receptor blocker comparators (n = 10,384), there were no significant differences in cardiovascular outcomes. There is no evidence that dihydropyridine calcium channel blockers are superior to other antihypertensive agents in Asian populations for the treatment of hypertension. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes: A Comparative Effectiveness Study.

PubMed

Schroeder, Emily B; Chonchol, Michel; Shetterly, Susan M; Powers, J David; Adams, John L; Schmittdiel, Julie A; Nichols, Gregory A; O'Connor, Patrick J; Steiner, John F

2018-05-07

In individuals with diabetes, the comparative effectiveness of add-on antihypertensive medications added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on the risk of significant kidney events is unknown. We used an observational, multicenter cohort of 21,897 individuals with diabetes to compare individuals who added β -blockers, dihydropyridine calcium channel blockers, loop diuretics, or thiazide diuretics to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We examined the hazard of significant kidney events, cardiovascular events, and death using Cox proportional hazard models with propensity score weighting. The composite significant kidney event end point was defined as the first occurrence of a ≥30% decline in eGFR to an eGFR<60 ml/min per 1.73 m 2 , initiation of dialysis, or kidney transplant. The composite cardiovascular event end point was defined as the first occurrence of hospitalization for acute myocardial infarction, acute coronary syndrome, stroke, or congestive heart failure; coronary artery bypass grafting; or percutaneous coronary intervention, and it was only examined in those free of cardiovascular disease at baseline. Over a maximum of 5 years, there were 4707 significant kidney events, 1498 deaths, and 818 cardiovascular events. Compared with thiazide diuretics, hazard ratios for significant kidney events for β -blockers, calcium channel blockers, and loop diuretics were 0.81 (95% confidence interval, 0.74 to 0.89), 0.67 (95% confidence interval, 0.58 to 0.78), and 1.19 (95% confidence interval, 1.00 to 1.41), respectively. Compared with thiazide diuretics, hazard ratios of mortality for β -blockers, calcium channel blockers, and loop diuretics were 1.19 (95% confidence interval, 0.97 to 1.44), 0.73 (95% confidence interval, 0.52 to 1.03), and 1.67 (95% confidence interval, 1.31 to 2.13), respectively. Compared with thiazide diuretics, hazard ratios of cardiovascular events for β -blockers, calcium channel blockers, and loop diuretics compared with thiazide diuretics were 1.65 (95% confidence interval, 1.39 to 1.96), 1.05 (95% confidence interval, 0.80 to 1.39), and 1.55 (95% confidence interval, 1.05 to 2.27), respectively. Compared with thiazide diuretics, calcium channel blockers were associated with a lower risk of significant kidney events and a similar risk of cardiovascular events. Copyright © 2018 by the American Society of Nephrology.

Bio-inspired voltage-dependent calcium channel blockers.

PubMed

Yang, Tingting; He, Lin-Ling; Chen, Ming; Fang, Kun; Colecraft, Henry M

2013-01-01

Ca(2+) influx via voltage-dependent CaV1/CaV2 channels couples electrical signals to biological responses in excitable cells. CaV1/CaV2 channel blockers have broad biotechnological and therapeutic applications. Here we report a general method for developing novel genetically encoded calcium channel blockers inspired by Rem, a small G-protein that constitutively inhibits CaV1/CaV2 channels. We show that diverse cytosolic proteins (CaVβ, 14-3-3, calmodulin and CaMKII) that bind pore-forming α1-subunits can be converted into calcium channel blockers with tunable selectivity, kinetics and potency, simply by anchoring them to the plasma membrane. We term this method 'channel inactivation induced by membrane-tethering of an associated protein' (ChIMP). ChIMP is potentially extendable to small-molecule drug discovery, as engineering FK506-binding protein into intracellular sites within CaV1.2-α1C permits heterodimerization-initiated channel inhibition with rapamycin. The results reveal a universal method for developing novel calcium channel blockers that may be extended to develop probes for a broad cohort of unrelated ion channels.

Antihypertensive drug associated angioedema: effect modification by race/ethnicity.

PubMed

Reichman, Marsha E; Wernecke, Michael; Graham, David J; Liao, Jiemin; Yap, John; Chillarige, Yoganand; Southworth, Mary Ross; Keeton, Stephine; Goulding, Margie R; Mott, Katrina; Kelman, Jeffrey A

2017-10-01

Assess angioedema risk with exposure to angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) compared with beta-blockers, by race/ethnicity. New-user cohorts of Medicare beneficiaries 65 years or older initiating ACEI, ARB, or beta-blocker treatment from March 2007 to March 2014 were constructed. Angioedema incidence rates by drug and race/ethnicity were computed for 1-30 and 31-365 days of treatment. Cox proportional hazards regression was used to examine angioedema risk between cohorts. Angioedema incidence rates (per 1000 person years) in beta-blocker users were 1.80 (whites), 4.11 (blacks), 1.89 (Asians), and 2.10 (Hispanics); in ACEI users, 4.03, 23.77, 2.94, and 4.27; and in ARB users, 1.73, 3.11, 1.10, and 1.90, respectively. Incidence rates were significantly higher in the first 30 days of exposure for all drug × race/ethnic groups. Overall, angioedema risk increased among ACEI users (hazard ratio, 2.91; 95% confidence interval, 2.75-3.07) but not ARB users (0.93, 0.85-1.02) versus beta-blocker users. Angioedema risk with ACEIs versus beta-blockers increased more in blacks (6.28, 5.44-7.24) than whites (2.33, 2.19-2.48), Hispanics (2.04, 1.36-3.07), and Asians (1.48, 0.94-2.35). Compared with white beta-blocker users, angioedema risk was increased 2.9-fold in whites, 20.2-fold in blacks, and 2.3-fold in other race/ethnic groups combined during the first 30 days of ACEI exposure. There was significant effect modification of angioedema risk by race and ACEI use for blacks, but not for other race/ethnicity groups. Angioedema risk was significantly greater in the first 30 days of exposure for all, and highest among blacks. Copyright © 2017 John Wiley & Sons, Ltd.

Layered transition metal carboxylates: efficient reusable heterogeneous catalyst for epoxidation of olefins.

PubMed

Sen, Rupam; Bhunia, Susmita; Mal, Dasarath; Koner, Subratanath; Miyashita, Yoshitaro; Okamoto, Ken-Ichi

2009-12-01

Layered metal carboxylates [M(malonato)(H(2)O)(2)](n) (M = Ni(II) and Mn(II)) that have a claylike structure have been synthesized hydrothermally and characterized. The interlayer separation in these layered carboxylates is comparable to that of the intercalation distance of the naturally occurring clay materials or layered double hydroxides (LDHs). In this study, we have demonstrated that, instead of intercalating the metal complex into layers of the clay or LDH, layered transition metal carboxylates, [M(malonato)(H(2)O)(2)](n), as such can be used as a recyclable heterogeneous catalyst in olefin epoxidation reaction. Metal carboxylates [M(malonato)(H(2)O)(2)](n) exhibit excellent catalytic performance in olefin epoxidation reaction.

The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes

PubMed Central

Kumagai, Kousuke; Kubo, Mitsuhiko; Imai, Shinji; Toyoda, Futoshi; Maeda, Tsutomu; Okumura, Noriaki; Matsuura, Hiroshi; Matsusue, Yoshitaka

2013-01-01

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl− current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl− conductance. The TNFα-evoked Cl− current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA. PMID:24084720

L-type voltage-dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2-induced neuronal apoptosis.

PubMed

Yagami, Tatsurou; Yamamoto, Yasuhiro; Kohma, Hiromi; Nakamura, Tsutomu; Takasu, Nobuo; Okamura, Noboru

2013-03-01

Snake venom group IA secretory phospholipase A2 (sPLA2-IA) is known as a neurotoxin. Snake venom sPLA2s are neurotoxic in vivo and in vitro, causing synergistic neurotoxicity to cortical cultures when applied with toxic concentrations of glutamate. However, it has not yet been cleared sufficiently how sPLA2-IA exerts neurotoxicity. Here, we found sPLA2-IA induced neuronal cell death in a concentration-dependent manner. This death was a delayed response requiring a latent time for 6h. sPLA2-IA-induced neuronal cell death was accompanied with apoptotic blebbing, condensed chromatin, and fragmented DNA, exhibiting apoptotic features. NMDA receptor blockers suppressed the neurotoxicity of sPLA2-IA, but an AMPA receptor blocker did not. Interestingly, L-type voltage-dependent Ca(2+) channel (L-VDCC) blocker significantly protected neurons from the sPLA2-IA-induced apoptosis. On the other hand, neither N-VDCC blockers nor P/Q-VDCC blocker did. In conclusion, we demonstrated that sPLA2-IA induced neuronal cell death via apoptosis. Furthermore, the present study suggests that not only NMDA receptor but also L-VDCC contributed to the neurotoxicity of snake venom sPLA2-IA. Copyright © 2013 Elsevier Inc. All rights reserved.

[Occupational hazards and bladder cancer].

PubMed

Nizamova, R S

1991-01-01

Occupational exposure to health hazards was studied in 258 industrial workers who had developed cancer of the bladder against 454 matched controls. All the test subjects and controls were residents of the Tambov Province centers of chemical industry. Statistical significance (relative risk-4.7) was established for exposure to aromatic amines. For those contacting with aniline dyes the relative risk (RR) made up 2.4. The risk to develop bladder cancer in powder shops (RR-3.2) was attributed to the hazards of dyes and diphenylamine. In leather-shoe and textile industry the exposure to dyes was not safe (RR-6.1), neither was it to chemicals, oil products, pesticides, overheating (RR-3.2, 1.6, 3.2 and 2.9, respectively). It is stated that in line with a significant risk to develop bladder cancer at exposure to aromatic amines there exist a number of occupational factors contributing to this risk.

Approximated transport-of-intensity equation for coded-aperture x-ray phase-contrast imaging.

PubMed

Das, Mini; Liang, Zhihua

2014-09-15

Transport-of-intensity equations (TIEs) allow better understanding of image formation and assist in simplifying the "phase problem" associated with phase-sensitive x-ray measurements. In this Letter, we present for the first time to our knowledge a simplified form of TIE that models x-ray differential phase-contrast (DPC) imaging with coded-aperture (CA) geometry. The validity of our approximation is demonstrated through comparison with an exact TIE in numerical simulations. The relative contributions of absorption, phase, and differential phase to the acquired phase-sensitive intensity images are made readily apparent with the approximate TIE, which may prove useful for solving the inverse phase-retrieval problem associated with these CA geometry based DPC.

Highly planar diarylamine-fused porphyrins and their remarkably stable radical cations† †Electronic supplementary information (ESI) available. CCDC 1469154–1469160. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc02721k Click here for additional data file. Click here for additional data file.

PubMed Central

Fukui, Norihito; Cha, Wonhee; Shimizu, Daiki; Oh, Juwon

2017-01-01

Oxidative fusion reactions of meso-phenoxazino Ni(ii) porphyrin were found to be temperature dependent, giving rise to either a doubly phenylene-fused product at room temperature or a singly phenoxazine-fused product at 70 °C. The latter was further oxidized to a doubly phenoxazine-fused Ni(ii) porphyrin, which was subsequently converted to the corresponding free base porphyrin and Zn(ii) porphyrin. Compared to previously reported diphenylamine-fused porphyrins that displayed a molecular twist, doubly phenoxazine-fused porphyrins exhibited distinctly different properties owing to their highly planar structures, such as larger fluorescence quantum yields, formation of an offset face-to-face dimer both in solution and the solid state, and the generation of a mixed-valence π-radical cation dimer upon electrochemical oxidation. One-electron oxidation of the phenoxazine-fused Ni(ii) porphyrin with Magic Blue gave the corresponding radical cation, which was certainly stable and could be isolated by separation over a silica gel column but slowly chlorinated at the reactive β-positions in the solid state. This finding led to us to examine β,β′-dichlorinated phenoxazine-fused and diphenylamine-fused Ni(ii) porphyrins, which, upon treatment with Magic Blue, provided remarkably stable radical cations to an unprecedented level. It is actually possible to purify these radical cations by silica gel chromatography, and they can be stored for over 6 months without any sign of deterioration. Moreover, they exhibited no degradation even after the CH2Cl2 solution was washed with water. However, subtle structural differences (planar versus partly twisted) led to different crystal packing structures and solid-state magnetic properties. PMID:28451165

New Drugs for Pretreatment of Organophosphonate Intoxication

DTIC Science & Technology

1990-02-20

amineHydrochlorides 40 1 -Phenylcyclohexane-l-carboxylic Acid 41 Dialkylaminoalkyl 1 -Phenylcycloalkane-l-carboxylate Hydrochlorides 41 3 -Formyl-4,5...cyclopropyl-CH2)- 3 -(Dimethylamino)propyl 1 -Phenylcyclopropane-l-carboxylate Hydrochloride (PRE-150). The recrystallized yield was 18.2 g (53...Arylcycloalkyl)methyl]amines 8 ct,a-Dialkylphenethylamines 9 Dialkylaminoalkyl 1 -Phenylcycloalkane-l-carboxylates 10 3 -Dialkylaminoalkyl-4,5

Pharmacogenetic approach to losartan in Marfan patients: a starting point to improve dosing regimen?

PubMed

Falvella, Felicia Stefania; Marelli, Susan; Cheli, Stefania; Montanelli, Stefano; Viecca, Federico; Salvi, Lucia; Ferrara, Alfio; Clementi, Emilio; Trifirò, Giuliana; Pini, Alessandro

2016-09-01

Losartan is under evaluation for managing Marfan patients with aortic root dilatation. Cytochrome P450 (CYP) enzymes convert losartan to E3174 active metabolite. The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. We genotyped 53 paediatric Marfan patients treated with losartan. The rate of aortic root dilatation was evaluated using the delta z-score variation. Differences in tolerated losartan daily doses with respect to CYP metabolic classes were assessed through the Kruskal-Wallis test. The losartan daily dose spans from 0.16 to 2.50 mg/kg (median 1.10 mg/kg). As we expect from the pharmacokinetics pathway, we observe highest tolerated dose in CYP2C9 poor metabolisers (median 1.50 mg/kg, interquartile range 1.08-1.67 mg/kg); however, this difference is not statistically significant. The optimal dose of angiotensin receptor blocker is not known, and no data are available about losartan pharmacogenetic profile in Marfan syndrome; we have proposed a strategy to tackle this issue based on evaluating the major genetic polymorphisms involved in the losartan conversion into active carboxylic acid metabolite. Further studies are needed to support the use of genetic polymorphisms as predictors of the right dose of losartan.

8,10-Diiodo-2,6-dioxo-4λ-ioda-3,5-dioxatricyclo-[5.3.1.0]undeca-1(11),7,9-triene-9-carb-oxy-lic acid.

PubMed

Sheng, Daopeng; Han, Lu; Zhang, Yi; Yang, Yanzhao

2012-03-01

In the title compound, C(9)HI(3)O(6)·2H(2)O, the mol-ecule is located on a twofold axis that gives rise to disorder of the carboxyl group. This disorder is correlated with the disorder of one of the H atoms of the water mol-ecule. The carboxyl group is twisted relative to the attached benzene ring by 75.1 (4)°. The intra-molecular I⋯O distance is 2.112 (6) Å. Mol-ecules are linked via O-H⋯O hydrogen bonding, C-I⋯O halogen bonding, with I⋯O distances in the range 3.156 (5)-3.274 (6) Å, and dipolar C=O⋯C=O inter-actions between the carboxyl and carboxyl-ate groups, with an O⋯C distance of 2.944 (10) Å.

Evaluation of Skin Permeation of β-blockers for Topical Drug Delivery

PubMed Central

Chantasart, Doungdaw; Hao, Jinsong; Li, S. Kevin

2013-01-01

Purpose β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Methods Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. Results The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. Conclusions The present results suggest the possibility of topical treatment of hemangioma using β-blockers. PMID:23208385

Production of W/O/W (water-in-oil-in-water) multiple emulsions: droplet breakup and release of water.

PubMed

Schuch, Anna; Deiters, Philipp; Henne, Julius; Köhler, Karsten; Schuchmann, Heike P

2013-07-15

We investigate breakup of W/O/W double emulsion droplets at high viscosity ratios and coalescence of inner water droplets dependent on the dispersed phase content (DPC) of the inner emulsion. The rheological analyses of the inner emulsions confirm the behavior expected from literature - increasing viscosity with increasing DPC and elastic behavior for high DPC. The resulting droplet sizes seem to be influenced only by the viscosity ratio calculated using the viscosity of the inner emulsion. An influence of the elastic properties of the inner emulsions could not be observed. Moreover, breakup of double emulsion droplets seems to follow the same rules as breakup of Newtonian droplets. In the second part of the paper we focus on the release of water from double emulsions by coalescence. A direct correlation between resulting double emulsion droplet sizes and encapsulation efficiency was found for each system. The initial inner dispersed phase content has a big influence on the release rate. This can partly be explained by the influence of the dispersed phase content on collision rate. Moreover, it was found that for high internal phase concentrations inner droplets coalesce with each other. The so formed bigger inner droplets seem to increase the overall release rate. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional mapping of hospitals by diagnosis-dominant case-mix analysis

PubMed Central

Fushimi, Kiyohide; Hashimoto, Hideki; Imanaka, Yuichi; Kuwabara, Kazuaki; Horiguchi, Hiromasa; Ishikawa, Kohichi B; Matsuda, Shinya

2007-01-01

Background Principles and methods for the allocation of healthcare resources among healthcare providers have long been health policy research issues in many countries. Healthcare reforms including the development of a new case-mix system, Diagnosis Procedure Combination (DPC), and the introduction of a DPC-based payment system are currently underway in Japan, and a methodology for adequately assessing the functions of healthcare providers is needed to determine healthcare resource allocations. Methods By two-dimensional mapping of the rarity and complexity of diagnoses for patients receiving treatment, we were able to quantitatively demonstrate differences in the functions of different healthcare service provider groups. Results On average, inpatients had diseases that were 3.6-times rarer than those seen in outpatients, while major teaching hospitals treated inpatients with diseases 3.0-times rarer on average than those seen at small hospitals. Conclusion We created and evaluated a new indicator for DPC, the diagnosis-dominant case-mix system developed in Japan, whereby the system was used to assess the functions of healthcare service providers. The results suggest that it is possible to apply the case-mix system to the integrated evaluation of outpatient and inpatient healthcare services and to the appropriate allocation of healthcare resources among health service providers. PMID:17425788

Isolation of a diphenylamine-degrading bacterium and characterization of its metabolic capacities, bioremediation and bioaugmentation potential.

PubMed

Perruchon, Chiara; Batianis, Christos; Zouborlis, Stelios; Papadopoulou, Evangelia S; Ntougias, Spyridon; Vasileiadis, Sotirios; Karpouzas, Dimitrios G

2015-12-01

The antioxidant diphenylamine (DPA) is used in fruit-packaging plants for the control of the physiological disorder apple scald. Its use results in the production of DPA-contaminated wastewater which should be treated before finally discharged. Biological treatment systems using tailored-made microbial inocula with specific catabolic activities comprise an appealing and sustainable solution. This study aimed to isolate DPA-degrading bacteria, identify the metabolic pathway of DPA and evaluate their potential for future implementation in bioremediation and biodepuration applications. A Pseudomonas putida strain named DPA1 able to rapidly degrade and utilize DPA as the sole C and N source was enriched from a DPA-contaminated soil. The isolated strain degraded spillage-level concentrations of DPA in liquid culture (2000 mg L(-1)) and in contaminated soil (1000 mg kg(-1)) and metabolized DPA via the transient formation of aniline and catechol. Further evidence for the bioremediation and biodepuration potential of the P. putida strain DPA1 was provided by its capacity to degrade the post-harvest fungicide ortho-phenylphenol (OPP), concurrently used by the fruit-packaging plants, although at slower rates and DPA in a wide range of pH (4.5-9) and temperatures (15-37 °C). These findings revealed the high potential of the P. putida strain DPA1 for use in future soil bioremediation strategies and/or as start-up inocula in wastewater biodepuration systems.

WE-AB-207A-09: Optimization of the Design of a Moving Blocker for Cone-Beam CT Scatter Correction: Experimental Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Ouyang, L; Jia, X

Purpose: A moving blocker based strategy has shown promising results for scatter correction in cone-beam computed tomography (CBCT). Different geometry designs and moving speeds of the blocker affect its performance in image reconstruction accuracy. The goal of this work is to optimize the geometric design and moving speed of the moving blocker system through experimental evaluations. Methods: An Elekta Synergy XVI system and an anthropomorphic pelvis phantom CIRS 801-P were used for our experiment. A blocker consisting of lead strips was inserted between the x-ray source and the phantom moving back and forth along rotation axis to measure the scattermore » signal. Accoriding to our Monte Carlo simulation results, three blockers were used, which have the same lead strip width 3.2mm and different gap between neighboring lead strips, 3.2, 6.4 and 9.6mm. For each blocker, three moving speeds were evaluated, 10, 20 and 30 pixels per projection (on the detector plane). Scatter signal in the unblocked region was estimated by cubic B-spline based interpolation from the blocked region. CBCT image was reconstructed by a total variation (TV) based algebraic iterative reconstruction (ART) algorithm from the partially blocked projection data. Reconstruction accuracy in each condition is quantified as CT number error of region of interest (ROI) by comparing to a CBCT reconstructed image from analytically simulated unblocked and scatter free projection data. Results: Highest reconstruction accuracy is achieved when the blocker width is 3.2 mm, the gap between neighboring lead strips is 9.6 mm and the moving speed is 20 pixels per projection. RMSE of the CT number of ROIs can be reduced from 436 to 27. Conclusions: Image reconstruction accuracy is greatly affected by the geometry design of the blocker. The moving speed does not have a very strong effect on reconstruction result if it is over 20 pixels per projection.« less

β-Blocker Continuation After Noncardiac Surgery

PubMed Central

Kwon, Steve; Thompson, Rachel; Florence, Michael; Maier, Ronald; McIntyre, Lisa; Rogers, Terry; Farrohki, Ellen; Whiteford, Mark; Flum, David R.

2014-01-01

Background Despite limited evidence of effect, β-blocker continuation has become a national quality improvement metric. Objective To determine the effect of β-blocker continuation on outcomes in patients undergoing elective noncardiac surgery. Design, Setting, and Patients The Surgical Care and Outcomes Assessment Program is a Washington quality improvement benchmarking initiative based on clinical data from more than 55 hospitals. Linking Surgical Care and Outcomes Assessment Program data to Washington’s hospital admission and vital status registries, we studied patients undergoing elective colorectal and bariatric surgical procedures at 38 hospitals between January 1, 2008, and December 31, 2009. Main Outcome Measures Mortality, cardiac events, and the combined adverse event of cardiac events and/or mortality. Results Of 8431 patients, 23.5% were taking β-blockers prior to surgery (mean [SD] age, 61.9 [13.7] years; 63.1% were women). Treatment with β-blockers was continued on the day of surgery and during the postoperative period in 66.0% of patients. Continuation of β-blockers both on the day of surgery and postoperatively improved from 57.2% in the first quarter of 2008 to 71.3% in the fourth quarter of 2009 (P value <.001). After adjusting for risk characteristics, failure to continue β-blocker treatment was associated with a nearly 2-fold risk of 90-day combined adverse event (odds ratio, 1.97; 95% CI, 1.19-3.26). The odds were even greater among patients with higher cardiac risk (odds ratio, 5.91; 95% CI, 1.40-25.00). The odds of combined adverse events continued to be elevated 1 year postoperatively (odds ratio, 1.66; 95% CI, 1.08-2.55). Conclusions β-Blocker continuation on the day of and after surgery was associated with fewer cardiac events and lower 90-day mortality. A focus on β-blocker continuation is a worthwhile quality improvement target and should improve patient outcomes. PMID:22249847

A 32 mm  ×  32 mm  ×  22 mm monolithic LYSO:Ce detector with dual-sided digital photon counter readout for ultrahigh-performance TOF-PET and TOF-PET/MRI

NASA Astrophysics Data System (ADS)

Borghi, Giacomo; Peet, Bart Jan; Tabacchini, Valerio; Schaart, Dennis R.

2016-07-01

New applications for positron emission tomography (PET) and combined PET/magnetic resonance imaging (MRI) are currently emerging, for example in the fields of neurological, breast, and pediatric imaging. Such applications require improved image quality, reduced dose, shorter scanning times, and more precise quantification. This can be achieved by means of dedicated scanners based on ultrahigh-performance detectors, which should provide excellent spatial resolution, precise depth-of-interaction (DOI) estimation, outstanding time-of-flight (TOF) capability, and high detection efficiency. Here, we introduce such an ultrahigh-performance TOF/DOI PET detector, based on a 32 mm  ×  32 mm  ×  22 mm monolithic LYSO:Ce crystal. The 32 mm  ×  32 mm front and back faces of the crystal are coupled to a digital photon counter (DPC) array, in so-called dual-sided readout (DSR) configuration. The fully digital detector offers a spatial resolution of ~1.1 mm full width at half maximum (FWHM)/~1.2 mm mean absolute error, together with a DOI resolution of ~2.4 mm FWHM, an energy resolution of 10.2% FWHM, and a coincidence resolving time of 147 ps FWHM. The time resolution closely approaches the best results (135 ps FWHM) obtained to date with small crystals made from the same material coupled to the same DPC arrays, illustrating the excellent correction for optical and electronic transit time spreads that can be achieved in monolithic scintillators using maximum-likelihood techniques for estimating the time of interaction. The performance barely degrades for events with missing data (up to 6 out of 32 DPC dies missing), permitting the use of almost all events registered under realistic acquisition conditions. Moreover, the calibration procedures and computational methods used for position and time estimation follow recently made improvements that make them fast and practical, opening up realistic perspectives for using DSR monolithic scintillator detectors in TOF-PET and TOF-PET/MRI systems.

Synthesis and characterization of silver nanoparticles from (bis)alkylamine silver carboxylate precursors.

PubMed

Uznanski, Pawel; Zakrzewska, Joanna; Favier, Frederic; Kazmierski, Slawomir; Bryszewska, Ewa

2017-01-01

A comparative study of amine and silver carboxylate adducts [R 1 COOAg-2(R 2 NH 2 )] (R 1  = 1, 7, 11; R 2  = 8, 12) as a key intermediate in NPs synthesis is carried out via differential scanning calorimetry, solid-state FT-infrared spectroscopy, 13 C CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and various solution NMR spectroscopies ( 1 H and 13 C NMR, pulsed field gradient spin-echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination as opposed to bridging bidentate coordination of pure silver carboxylates resulting from the formation of dimeric units. All complexes are packed as lamellar bilayer structures. Silver carboxylate/amine complexes show one first-order melting transition. The evidence presented in this study shows that phase behavior of monovalent metal carboxylates are controlled, mainly, by head group bonding. In solution, insoluble silver salt is stabilized by amine molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate complex as precursor, silver nanoparticles were fabricated. During high-temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce silver nanoparticles of small size. NPs are stabilized by strongly interacting carboxylate and trace amounts of amine derived from the silver precursor interacting with carboxylic acid. A corresponding aliphatic amide obtained from silver precursor at high-temperature reaction conditions is not taking part in the stabilization. Combining NMR techniques with FTIR, it was possible to follow an original stabilization mechanism. Graphical abstractThe synthesis of a series (bis)alkylamine silver(I) carboxylate complexes in nonpolar solvents were carried out and fully characterized both in the solid and solution. Carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination. The complexes form layered structures which thermally decompose forming nanoparticles stabilized only by aliphatic carboxylates.

Prevalence and prognostic significance of adrenergic escape during chronic beta-blocker therapy in chronic heart failure.

PubMed

Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

2009-02-01

Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60). We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

Prevalence and prognostic significance of adrenergic escape during chronic β-blocker therapy in chronic heart failure

PubMed Central

Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

2009-01-01

Aims Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to β-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different β-blocker agents and doses. Methods and results This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable β-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual β-blocker agents used and the dose equivalent taken, the prevalence of AE was 31–39%. Norepinephrine levels neither correlated with heart rate (r = 0.02; 95% CI: −0.08–0.11; P = 0.74) nor were they related to underlying rhythm (P = 0.09) or the individual β-blocker agent used (P = 0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387–2.645; χ2: 15.60). Conclusion We verified the presence of AE in CHF patients on chronic stable β-blocker therapy, irrespective of the individual β-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape. PMID:19168516

Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow, Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

PubMed Central

2015-01-01

Study Overview The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Conclusion and Significance Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system. PMID:25915506

Achieving ventricular rate control using metoprolol in β-blocker-naive patients vs patients on chronic β-blocker therapy.

PubMed

Kuang, Patricia; Mah, Nathan D; Barton, Cassie A; Miura, Andrea J; Tanas, Laura R; Ran, Ran

2016-03-01

The objective of the study is to evaluate the difference in ventricular rate control using an intravenous (IV) metoprolol regimen commonly used in clinical practice in patients receiving chronic β-blocker therapy compared to patients considered β-blocker naive admitted to the emergency department (ED) for atrial fibrillation (AF) with rapid ventricular rate. A single-center retrospective cohort study of adult ED patients who were admitted with a rapid ventricular rate of 120 beats per minute (bpm) or greater and treated with IV metoprolol was performed. Rate control was defined as either a decrease in ventricular rate to less than 100 bpm or a 20% decrease in heart rate to less than 120 bpm after metoprolol administration. Patient demographics, differences in length of stay, and adverse events were recorded. A total of 398 patients were included in the study, with 79.4% (n=316) receiving chronic β-blocker therapy. Patients considered to be β-blocker naive were more likely to achieve successful rate control with IV metoprolol compared to patients on chronic β-blocker therapy (56.1% vs 42.4%; P=.03). β-Blocker-naive status was associated with a shorter length of stay in comparison to patients receiving chronic β-blocker therapy (1.79 vs 2.64 days; P<.01). Intravenous metoprolol for the treatment of atrial fibrillation with rapid ventricular rate was associated with a higher treatment response in patients considered β-blocker naive compared to patients receiving chronic β-blocker therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Initiation of Beta-Blocker Therapy and Depression After Acute Myocardial Infarction

PubMed Central

Ranchord, Anil M.; Spertus, John A.; Buchanan, Donna M.; Gosch, Kensey L.; Chan, Paul S.

2016-01-01

Introduction Although beta (β)-blockers reduce mortality after acute myocardial infarction (AMI), early reports linking β-blocker use with subsequent depression have potentially limited their use in vulnerable patients. We sought to provide empirical evidence to support or refute this concern by examining the association between β-blocker initiation and change in depressive symptoms in AMI patients. Methods Using data from 2 US multi-center, prospective registries of AMI patients, we examined 1-, 6-, and 12-month changes in depressive symptoms after the index hospitalization among patients who were β-blocker naïve on admission. Depressive symptoms were assessed using the validated 8-item Patient Health Questionnaire (PHQ-8), which rates depressive symptoms from 0 to 24, with higher scores indicating more depressive symptoms. A propensity-matched repeated measures linear regression model was used to compare change in depressive symptoms among patients who were and were not initiated on a β-blocker after AMI. Results Of 3470 AMI patients who were β-blocker naïve on admission, 3190 (91.9%) were initiated on a β-blocker and 280 (8.1%) were not. Baseline PHQ-8 scores were higher in patients not initiated on a β-blocker (mean 5.78 ± 5.45 vs. 4.88 ± 5.11, P=0.005). PHQ-8 scores were progressively lower at 1, 6 and 12 months in both the β-blocker (mean decrease at 12 months, 1.16; p<0.0001) and no β-blocker groups (mean decrease, 1.71; p<0.0001). After propensity matching 201 untreated patients with 567 treated patients, initiation of β-blocker therapy was not associated with a difference in mean change in PHQ-8 scores at 1, 6 or 12 months after AMI (absolute mean difference with β-blocker initiation at 12 months of 0.08, 95% CI: −0.81 to 0.96, P=0.86). Conclusions Initiation of β-blocker therapy after AMI was not associated with an increase in depressive symptoms. Restricting β-blocker use because of concerns about depression appears unwarranted and may lead to under-treatment of AMI patients. PMID:26995368

Synthesis and characterization of bifunctional surfaces with tunable functional group pairs

NASA Astrophysics Data System (ADS)

Galloway, John M.; Kung, Mayfair; Kung, Harold H.

2016-06-01

Grafting of pairs of functional groups onto a silica surface was demonstrated by tethering both terminals of an organochlorosilane precursor molecule, Cl2(CH3)Si(CH2)4(CO)(OSi(i-Pr)2)(CH2)2Si(CH3)Cl2, that possess a cleavable silyl ester bond, onto a silica surface. Hydrolytic cleavage of the silyl ester bond of the grafted molecule resulted in the generation of organized pairs of carboxylic acid and organosilanol groups. This organosilanol moiety was easily transformed into other functional groups through condensation reactions to form, together with the neighboring acid group, pairs such as carboxylic acid/secondary amine, carboxylic acid/pyridine, and carboxylic acid/phosphine. In the case of carboxylic acid/amine pairing, there was evidence of the formation of amide. A sample grafted with amine-carboxylic acid pairs was three times more active (per free amine) than a sample without such pairs for the nitroaldol condensation of 4-nitrobenzaldehyde and nitromethane.

Syntheses, structures and magnetic properties of four coordination polymers based on nitrobenzene dicarboxylate and various N-donor coligands

NASA Astrophysics Data System (ADS)

Li, Gui-Lian; Yin, Wei-Dong; Liu, Guang-Zhen; Ma, Lu-Fang; Wang, Li-Ya

2014-12-01

Four new coordination polymers {[Ni(4-Nbdc)(bpa)(H2O)]}n (1), {[Co(4-Nbdc)(bpp) (H2O)]}n (2), {[Ni(4-Nbdc)(bpp)(H2O)]·H2O}n (3), and {[Mn2(3-Nbdc)2(bib)3]·2H2O}n (4) (4-Nbdc=4-nitrobenzene-1,2-dicarboxylate, 3-Nbdc=3-nitrobenzene-1,2-dicarboxylate, bpa=1,2-bi(4-pyridyl)ethane, bpp=1,3-bis(4-pyridyl)propane, and bib=1,4-bis(1-imidazoly)benzene), were synthesized by hydrothermal reactions, and characterized by single-crystal X-ray diffractions, elemental analysis, FT-IR, PXRD, TGA and magnetic analysis. Complexes 1 and 2 display quasi-trapezoidal chain and brick-wall layer, and both of them contain metal-carboxylate binuclear units. Complexes 3 and 4 exhibit three-dimensional frameworks with the (66) dia topology and (44.610.8)(44.62) fsc topology, and both of them contain metal-carboxylate chains. The carboxyl groups with syn-anti coordination mode mediate effectively the weak ferromagnetic coupling interaction within Ni(II)-carboxylate binuclear in 1 (J=1.27 cm-1) and Ni(II)-carboxylate chain in 3 (J=1.44 cm-1), respectively, and the carboxyl groups with anti-anti coordination mode leads to the classic antiferromagnetic coupling interaction within Mn(II)-carboxylate chain in 4 (J=-0.77 cm-1).

Application of the desulfurization of phenothiazines for a sensitive detection method by high-performance liquid chromatography.

PubMed

Shimada, K; Mino, T; Nakajima, M; Wakabayashi, H; Yamato, S

1994-11-04

A simple and sensitive high-performance liquid chromatographic (HPLC) method for the determination of phenothiazine (PHE) is described. PHE is converted to diphenylamine (DIP) by desulfurization with Raney nickel catalyst. DIP is highly sensitive to electrochemical detection. The calibration graph for PHE quantification after desulfurization was linear between 0.1 and 2.0 ng per injection. The detection limit (signal-to-noise ratio = 3) of PHE after desulfurization was 10 pg, which is twenty times higher than that of the parent compound PHE. The proposed desulfurization technique was applied to other PHE-related compounds. The structural confirmation of the desulfurized product of PHE was carried out by LC-MS using atmospheric pressure chemical ionization.

Polythermal investigation of viscosity of solution of metal carboxylates in VIK-grade mixed carboxylic acids: Yttrium and gadolinium carboxylates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mezhov, E.A.; Samatov, A.V.; Troyanovskii, L.V.

Kinematic viscosities have been measured for solutions of yttrium and gadolinium carboxylates in grade VIK mixed carboxylic acids (MCA). It has been established that the optimal fluidity of these metal carboxylate solutions for application to articles is reached at 333 K. A regression model has been developed to describe the concentration and temperature dependences of the viscosity of yttrium- and gadolinium-containing MCA solutions. 2 refs., 3 tabs.

Structural environments of carboxyl groups in natural organic molecules from terrestrial systems. Part 2: 2D NMR spectroscopy

NASA Astrophysics Data System (ADS)

Deshmukh, Ashish P.; Pacheco, Carlos; Hay, Michael B.; Myneni, Satish C. B.

2007-07-01

Carboxyl groups are abundant in natural organic molecules (NOM) and play a major role in their reactivity. The structural environments of carboxyl groups in IHSS soil and river humic samples were investigated using 2D NMR (heteronuclear and homonuclear correlation) spectroscopy. Based on the 1H- 13C heteronuclear multiple-bond correlation (HMBC) spectroscopy results, the carboxyl environments in NOM were categorized as Type I (unsubstituted and alkyl-substituted aliphatic/alicyclic), Type II (functionalized carbon substituted), Type IIIa, b (heteroatom and olefin substituted), and Type IVa, b (5-membered heterocyclic aromatic and 6-membered aromatic). The most intense signal in the HMBC spectra comes from the Type I carboxyl groups, including the 2JCH and 3JCH couplings of unsubstituted aliphatic and alicyclic acids, though this spectral region also includes the 3JCH couplings of Type II and III structures. Type II and III carboxyls have small but detectable 2JCH correlations in all NOM samples except for the Suwannee River humic acid. Signals from carboxyls bonded to 5-membered aromatic heterocyclic fragments (Type IVa) are observed in the soil HA and Suwannee River FA, while correlations to 6-membered aromatics (Type IVb) are only observed in Suwannee River HA. In general, aromatic carboxylic acids may be present at concentrations lower than previously imagined in these samples. Vibrational spectroscopy results for these NOM samples, described in an accompanying paper [Hay M. B. and Myneni S. C. B. (2007) Structural environments of carboxyl groups in natural organic molecules from terrestrial systems. Part 1: Infrared spectroscopy. Geochim. Cosmochim. Acta (in press)], suggest that Type II and Type III carboxylic acids with α substituents (e.g., -OH, -OR, or -CO 2H) constitute the majority of carboxyl structures in all humic substances examined. Furoic and salicylic acid structures (Type IV) are also feasible fragments, albeit as minor constituents. The vibrational spectroscopy results also suggest that much of the "Type I" signal observed in the HMBC spectrum is due to carboxylic acid esters and possibly α-substituted alicyclic acids.

Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid.

PubMed

Mohana, Marimuthu; Thomas Muthiah, Packianathan; McMillen, Colin D

2017-06-01

In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil-5-bromothiophene-2-carboxylic acid (1/1), C 5 H 3 BrO 2 S·C 4 H 3 FN 2 O 2 , (I), and 5-fluorouracil-thiophene-2-carboxylic acid (1/1), C 4 H 3 FN 2 O 2 ·C 5 H 4 O 2 S, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid-acid R 2 2 (8) homosynthon (O-H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R 2 2 (8) motif] via a pair of N-H...O hydrogen bonds. The crystal structures are further stabilized by C-H...O interactions in (II) and C-Br...O interactions in (I). In both crystal structures, π-π stacking and C-F...π interactions are also observed.

EFFECT OF SYSTEMIC BETA-BLOCKERS, ACE INHIBITORS, AND ANGIOTENSIN RECEPTOR BLOCKERS ON DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION.

PubMed

Thomas, Akshay S; Redd, Travis; Hwang, Thomas

2015-10-01

Recent studies have suggested that the use of systemic beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models. The purpose of this study is to evaluate if these agents have a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration. In this single-center retrospective case-control study, the charts of 250 patients with neovascular age-related macular degeneration were compared with those of 250 controls with dry age-related macular degeneration. Charts were reviewed for current and past use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Frequency tables were generated, and associations were examined using chi-square tests, t-tests, and multivariate logistic regression. There was no statistically significant difference between rates of beta-blocker use (P = 0.57), angiotensin-converting enzyme inhibitors use (P = 0.20), or angiotensin receptor blockers use (P = 0.61) between the 2 groups. Additionally, there was no statistically significant difference between rates of use of combinations of the above drugs between the two groups. Although there is growing evidence that beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models, these medications do not seem to confer a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration.

Facile preparation of oxazole-4-carboxylates and 4-ketones from aldehydes using 3-oxazoline-4-carboxylates as intermediates.

PubMed

Murai, Kenichi; Takahara, Yusuke; Matsushita, Tomoyo; Komatsu, Hideyuki; Fujioka, Hiromichi

2010-08-06

A novel 2-step synthesis of oxazole-4-carboxylates from aldehydes was developed, which is characterized by the utilization of 3-oxazoline-4-carboxylates as synthetic intermediates. The facile preparation of 4-keto-oxazole derivatives from 3-oxazoline-4-carboxylates based on their interesting reactivity toward Grignard reagents is also described.

In utero imaging of mouse embryonic development with optical coherence tomography

NASA Astrophysics Data System (ADS)

Syed, Saba H.; Dickinson, Mary E.; Larin, Kirill V.; Larina, Irina V.

2011-03-01

Studying progression of congenital diseases in animal models can greatly benefit from live embryonic imaging Mouse have long served as a model of mammalian embryonic developmental processes, however, due to intra-uterine nature of mammalian development live imaging is challenging. In this report we present results on live mouse embryonic imaging in utero with Optical Coherence Tomography. Embryos from 12.5 through 17.5 days post-coitus (dpc) were studied through the uterine wall. In longitudinal studies, same embryos were imaged at developmental stages 13.5, 15.5 and 17.5 dpc. This study suggests that OCT can serve as a powerful tool for live mouse embryo imaging. Potentially this technique can contribute to our understanding developmental abnormalities associated with mutations, toxic drugs.

Automated in-tube solid-phase microextraction coupled with liquid chromatography/electrospray ionization mass spectrometry for the determination of beta-blockers and metabolites in urine and serum samples.

PubMed

Kataoka, H; Narimatsu, S; Lord, H L; Pawliszyn, J

1999-10-01

The technique of automated in-tube solid-phase microextraction (SPME) coupled with liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) was evaluated for the determination of beta-blockers in urine and serum samples. In-tube SPME is an extraction technique for organic compounds in aqueous samples, in which analytes are extracted from the sample directly into an open tubular capillary by repeated draw/eject cycles of sample solution. LC/MS analyses of beta-blockers were initially performed by liquid injection onto a LC column. Nine beta-blockers tested in this study gave very simple ESI mass spectra, and strong signals corresponding to [M + H]+ were observed for all beta-blockers. The beta-blockers were separated with a Hypersil BDS C18 column using acetonitrile/methanol/water/acetic acid (15:15:70:1) as a mobile phase. To optimize the extraction of beta-blockers, several in-tube SPME parameters were examined. The optimum extraction conditions were 15 draw/eject cycles of 30 microL of sample in 100 mM Tris-HCl (pH 8.5) at a flow rate of 100 microL/min using an Omegawax 250 capillary (Supelco, Bellefonte, PA). The beta-blockers extracted by the capillary were easily desorbed by mobile-phase flow, and carryover of beta-blockers was not observed. Using in-tube SPME/LC/ESI-MS with selected ion monitoring, the calibration curves of beta-blockers were linear in the range from 2 to 100 ng/mL with correlation coefficients above 0.9982 (n = 18) and detection limits (S/N = 3) of 0.1-1.2 ng/mL. This method was successfully applied to the analysis of biological samples without interference peaks. The recoveries of beta-blockers spiked into human urine and serum samples were above 84 and 71%, respectively. A serum sample from a patient administrated propranolol was analyzed using this method and both propranolol and its metabolites were detected.

SU-F-I-55: Performance Evaluation of Digital PET/CT: Medical Physics Basis for the Clinical Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, J; Knopp, MV; Miller, M

2016-06-15

Purpose: Replacement of conventional PMT-based detector with next generation digital photon counting (DPC) detector is a technology leap for PET imaging. This study evaluated the performance and characteristics of the DPC system and its stability within a 1 year time window following its installation focusing on the medical physics basis for clinical applications. Methods: A digital PET/CT scanner using 1:1 coupling of 23,040 crystal: detector elements was introduced and became operational at OSU. We tested and evaluated system performance and characteristics using NEMA NU2-2012. System stabilities in timing resolution, energy resolution, detector temperature and humidity (T&H) were monitored over 1-yr.more » Timing, energy and spatial resolution were characterized across clinically relevant count rate range. CQIE uniformity PET and NEMA IEC-Body PET with hot spheres varying with sizes and contrasts were performed. PET reconstructed in standard(4mm), High(2mm) and Ultra-High(1mm) definitions were evaluated. Results: NEMA results showed PET spatial resolution (mm-FWHM) from 4.01&4.14 at 1cm to 5.82&6.17 at 20cm in transverse & axial. 322±3ps timing and 11.0% energy resolution were measured. 5.7kcps/MBq system sensitivity with 24kcps/MBq effective sensitivity was obtained. The peak-NECR was ∼171kcps with the effective peak-NECR >650kcps@50kBq/mL. Scatter fraction was ∼30%, and the maximum trues was >900kcps. NEMA IQ demonstrated hot sphere contrast ranging from ∼62%±2%(10mm) to ∼88%±2%(22mm), cold sphere contrast of ∼86%±2%(28mm) and ∼89%±3%(37mm) and excellent uniformity. Monitoring 1-yr stability, it revealed ∼1% change in timing, ±0.4% change in energy resolution, and <10% variations in T&H. CQIE PET gave <3% SUV variances in axial. 60%–100% recovery coefficients across sphere sizes and contrast levels were achieved. Conclusion: Characteristics and stability of the next generation DPC PET detector system over an 1-yr time window was excellent and better than prior experiences. It demonstrated improved and robust system characteristics and performance in spatial resolution, sensitivity, timing and energy resolution, count rate and image quality. Michael Miller is an employee of Philips Healthcare.« less

A chromene and prenylated benzoic acid from Piper aduncum.

PubMed

Baldoqui, D C; Kato, M J; Cavalheiro, A J; Bolzani, V da S; Young, M C; Furlan, M

1999-08-01

In addition to nerolidol, 2',6'-dihydroxy-4'-methoxydihydrochalcone, methyl 2,2-dimethyl-8-(3'-methyl-2'-butenyl)-2H-1-chromene-6-carboxylate, methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate and methyl 8-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate, two new natural products were isolated from the leaves of Piper aduncum, 2,2-dimethyl-2H-1-chromene-6-carboxylic acid and 3-(3',7'-dimethyl-2',6'-octadienyl)-4-methoxybenzoic acid. The structures of the isolates were established based on analysis of spectroscopic data, including ES-MS. The DNA-damaging activity of the isolated compounds was also investigated against mutant strains of Saccharomyces cerevisiae.

Synthesis and characterization of silver nanoparticles from (bis)alkylamine silver carboxylate precursors

NASA Astrophysics Data System (ADS)

Uznanski, Pawel; Zakrzewska, Joanna; Favier, Frederic; Kazmierski, Slawomir; Bryszewska, Ewa

2017-03-01

A comparative study of amine and silver carboxylate adducts [R1COOAg-2(R2NH2)] (R1 = 1, 7, 11; R2 = 8, 12) as a key intermediate in NPs synthesis is carried out via differential scanning calorimetry, solid-state FT-infrared spectroscopy, 13C CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and various solution NMR spectroscopies (1H and 13C NMR, pulsed field gradient spin-echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of amine ligands are bound to silver ions via chelating bidentate type of coordination as opposed to bridging bidentate coordination of pure silver carboxylates resulting from the formation of dimeric units. All complexes are packed as lamellar bilayer structures. Silver carboxylate/amine complexes show one first-order melting transition. The evidence presented in this study shows that phase behavior of monovalent metal carboxylates are controlled, mainly, by head group bonding. In solution, insoluble silver salt is stabilized by amine molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate complex as precursor, silver nanoparticles were fabricated. During high-temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce silver nanoparticles of small size. NPs are stabilized by strongly interacting carboxylate and trace amounts of amine derived from the silver precursor interacting with carboxylic acid. A corresponding aliphatic amide obtained from silver precursor at high-temperature reaction conditions is not taking part in the stabilization. Combining NMR techniques with FTIR, it was possible to follow an original stabilization mechanism.

Influence of beta blockers on survival in dogs with severe subaortic stenosis.

PubMed

Eason, B D; Fine, D M; Leeder, D; Stauthammer, C; Lamb, K; Tobias, A H

2014-01-01

Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical. To determine the influence of beta blocker treatment on survival time in dogs with severe SAS. Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011. Fifty dogs met the inclusion criteria. Twenty-seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all-cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all-cause (P = .93) or cardiac-cause (P = .97) mortality analyses. Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death. Copyright © 2014 by the American College of Veterinary Internal Medicine.

BRIEF REPORT: β-Blocker Use Among Veterans with Systolic Heart Failure

PubMed Central

Sinha, Sanjai; Goldstein, Matthew; Penrod, Joan; Hochman, Tsivia; Kamran, Mohammad; Tenner, Craig; Cohen, Gabriela; Schwartz, Mark D

2006-01-01

BACKGROUND β-Blockers reduce mortality in patients with systolic chronic heart failure (CHF), yet prescription rates have remained low among primary care providers. OBJECTIVE To determine the β-blocker prescription rate among patients with systolic CHF at primary care Veterans Affairs (VA) clinics, its change over time; and to determine factors associated with nonprescription. DESIGN Retrospective chart review. SUBJECTS Seven hundred and forty-five patients with diagnostic codes for CHF followed in primary care clinics at 3 urban VA Medical Centers. MEASUREMENTS Rate of β-blocker prescription and comparison of patient characteristics between those prescribed versus those not prescribed β-blockers. RESULTS Only 368 (49%) had documented systolic CHF. Eighty-two percent (303/368) of these patients were prescribed a β-blocker. The prescription rate rose steadily over 3 consecutive 2-year time periods. Patients with more severely depressed ejection fractions were more likely to be on a β-blocker than patients with less severe disease. Independent predictors of nonprescription included chronic obstructive pulmonary disease, asthma, depression, and age. Patients under 65 years old were 12 times more likely to receive β-blockers than those over 85. CONCLUSION Primary care providers at VA Medical Centers achieved high rates of β-blocker prescription for CHF patients. Subgroups with relative contraindications had lower prescription rates and should be targeted for quality improvement initiatives. PMID:17105526

Induction of Cardiac Fibrosis by β-Blocker in G Protein-independent and G Protein-coupled Receptor Kinase 5/β-Arrestin2-dependent Signaling Pathways*

PubMed Central

Nakaya, Michio; Chikura, Satsuki; Watari, Kenji; Mizuno, Natsumi; Mochinaga, Koji; Mangmool, Supachoke; Koyanagi, Satoru; Ohdo, Shigehiro; Sato, Yoji; Ide, Tomomi; Nishida, Motohiro; Kurose, Hitoshi

2012-01-01

G-protein coupled receptors (GPCRs) have long been known as receptors that activate G protein-dependent cellular signaling pathways. In addition to the G protein-dependent pathways, recent reports have revealed that several ligands called “biased ligands” elicit G protein-independent and β-arrestin-dependent signaling through GPCRs (biased agonism). Several β-blockers are known as biased ligands. All β-blockers inhibit the binding of agonists to the β-adrenergic receptors. In addition to β-blocking action, some β-blockers are reported to induce cellular responses through G protein-independent and β-arrestin-dependent signaling pathways. However, the physiological significance induced by the β-arrestin-dependent pathway remains much to be clarified in vivo. Here, we demonstrate that metoprolol, a β1-adrenergic receptor-selective blocker, could induce cardiac fibrosis through a G protein-independent and β-arrestin2-dependent pathway. Metoprolol, a β-blocker, increased the expression of fibrotic genes responsible for cardiac fibrosis in cardiomyocytes. Furthermore, metoprolol induced the interaction between β1-adrenergic receptor and β-arrestin2, but not β-arrestin1. The interaction between β1-adrenergic receptor and β-arrestin2 by metoprolol was impaired in the G protein-coupled receptor kinase 5 (GRK5)-knockdown cells. Metoprolol-induced cardiac fibrosis led to cardiac dysfunction. However, the metoprolol-induced fibrosis and cardiac dysfunction were not evoked in β-arrestin2- or GRK5-knock-out mice. Thus, metoprolol is a biased ligand that selectively activates a G protein-independent and GRK5/β-arrestin2-dependent pathway, and induces cardiac fibrosis. This study demonstrates the physiological importance of biased agonism, and suggests that G protein-independent and β-arrestin-dependent signaling is a reason for the diversity of the effectiveness of β-blockers. PMID:22888001

Perindopril and β-blocker for the prevention of cardiac events and mortality in stable coronary artery disease patients: A EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) subanalysis.

PubMed

Bertrand, Michel E; Ferrari, Roberto; Remme, Willem J; Simoons, Maarten L; Fox, Kim M

2015-12-01

β-Blockers relieve angina/ischemia in stable coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors prevent CAD outcomes. In EUROPA, the angiotensin-converting enzyme inhibitor perindopril reduced cardiovascular outcomes in low-risk stable CAD patients over 4.2 years. This post hoc analysis examined whether the addition of perindopril to β-blocker in EUROPA had additional benefits on outcomes compared with standard therapy including β-blocker. EUROPA was a multicenter, double-blind, placebo-controlled, randomized trial in patients with documented stable CAD. Randomized EUROPA patients who received β-blocker at baseline were identified, and the effect on cardiovascular outcomes of adding perindopril or placebo was analyzed. Endpoints were the same as those in EUROPA. At baseline, 62% (n = 7534 [3789 on perindopril and 3745 on placebo]) received β-blocker. Treatment with perindopril/β-blocker reduced the relative risk of the primary end point (cardiovascular death, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 24% compared with placebo/β-blocker (HR, 0.76; 95% CI, 0.64-0.91; P = .002). Addition of perindopril also reduced fatal or nonfatal myocardial infarction by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and hospitalization for heart failure by 45% (HR, 0.55; 95% CI, 0.33-0.93; P = .025). Serious adverse drug reactions were rare in both groups, and cardiovascular death and hospitalizations occurred less often with perindopril/β-blocker. The addition of perindopril to β-blocker in stable CAD patients was safe and resulted in reductions in cardiovascular outcomes and mortality compared with standard therapy including β-blocker. Copyright © 2015 Elsevier Inc. All rights reserved.

Carbonate-Promoted Hydrogenation of Carbon Dioxide to Multicarbon Carboxylates

PubMed Central

2018-01-01

CO2 hydrogenation is a potential alternative to conventional petrochemical methods for making commodity chemicals and fuels. Research in this area has focused mostly on transition-metal-based catalysts. Here we show that hydrated alkali carbonates promote CO2 hydrogenation to formate, oxalate, and other C2+ carboxylates at elevated temperature and pressure in the absence of transition-metal catalysts or solvent. The reactions proceed rapidly, reaching up to 56% yield (with respect to CO32–) within minutes. Isotope labeling experiments indicate facile H2 and C–H deprotonations in the alkali cation-rich reaction media and identify probable intermediates for the C–C bond formations leading to the various C2+ products. The carboxylate salts are in equilibrium with volatile carboxylic acids under CO2 hydrogenation conditions, which may enable catalytic carboxylic acid syntheses. Our results provide a foundation for base-promoted and base-catalyzed CO2 hydrogenation processes that could complement existing approaches. PMID:29806007

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

PubMed

Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

2015-05-01

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels. © 2015 Wiley Publishing Asia Pty Ltd.

A Prospective Comparison of Intraluminal and Extraluminal Placement of the 9-French Arndt Bronchial Blocker in Adult Thoracic Surgery Patients.

PubMed

Templeton, T Wesley; Morris, Benjamin N; Goenaga-Diaz, Eduardo J; Forest, Daniel J; Hadley, Rhett; Moore, Blake A; Bryan, Yvon F; Royster, Roger L

2017-08-01

To compare the standard intraluminal approach with the placement of the 9-French Arndt endobronchial blocker with an extraluminal approach by measuring the time to positioning and other relevant intraoperative and postoperative parameters. A prospective, randomized, controlled trial. University hospital. The study comprised 41 patients (20 intraluminal, 21 extraluminal) undergoing thoracic surgery. Placement of a 9-French Arndt bronchial blocker either intraluminally or extraluminally. Comparisons between the 2 groups included the following: (1) time for initial placement, (2) quality of isolation at 1-hour intervals during one-lung ventilation, (3) number of repositionings during one-lung ventilation, and (4) presence or absence of a sore throat on postoperative days 1 and 2 and, if present, its severity. Median time to placement (min:sec) in the extraluminal group was statistically faster at 2:42 compared with 6:24 in the intraluminal group (p < 0.05). Overall quality of isolation was similar between groups, even though a significant number of blockers in both groups required repositioning (extraluminal 47%, intraluminal 40%, p > 0.05), and 1 blocker ultimately had to be replaced intraoperatively. No differences in the incidence or severity of sore throat postoperatively were observed. A statistically significant reduction in time to placement using the extraluminal approach without any differences in the rate of postoperative sore throat was observed. Whether placed intraluminally or extraluminally, a significant percentage of Arndt endobronchial blockers required at least one intraoperative repositioning. Copyright © 2017 Elsevier Inc. All rights reserved.

Production of carboxylic acid and salt co-products

DOEpatents

Hanchar, Robert J.; Kleff, Susanne; Guettler, Michael V.

2014-09-09

This invention provide processes for producing carboxylic acid product, along with useful salts. The carboxylic acid product that is produced according to this invention is preferably a C.sub.2-C.sub.12 carboxylic acid. Among the salts produced in the process of the invention are ammonium salts.

Development of selective blockers for Ca2+-activated Cl- channel using Xenopus laevis oocytes with an improved drug screening strategy

PubMed Central

Oh, Soo-Jin; Park, Jung Hwan; Han, Sungyu; Lee, Jae Kyun; Roh, Eun Joo; Lee, C Justin

2008-01-01

Background Ca2+-activated Cl- channels (CaCCs) participate in many important physiological processes. However, the lack of effective and selective blockers has hindered the study of these channels, mostly due to the lack of good assay system. Here, we have developed a reliable drug screening method for better blockers of CaCCs, using the endogeneous CaCCs in Xenopus laevis oocytes and two-electrode voltage-clamp (TEVC) technique. Results Oocytes were prepared with a treatment of Ca2+ ionophore, which was followed by a treatment of thapsigargin which depletes Ca2+ stores to eliminate any contribution of Ca2+ release. TEVC was performed with micropipette containing chelerythrine to prevent PKC dependent run-up or run-down. Under these conditions, Ca2+-activated Cl- currents induced by bath application of Ca2+ to oocytes showed stable peak amplitude when repetitively activated, allowing us to test several concentrations of a test compound from one oocyte. Inhibitory activities of commercially available blockers and synthesized anthranilic acid derivatives were tested using this method. As a result, newly synthesized N-(4-trifluoromethylphenyl)anthranilic acid with trifluoromethyl group (-CF3) at para position on the benzene ring showed the lowest IC50. Conclusion Our results provide an optimal drug screening strategy suitable for high throughput screening, and propose N-(4-trifluoromethylphenyl)anthranilic acid as an improved CaCC blocker. PMID:18959787

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

PubMed

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic

PubMed Central

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Abstract Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications. PMID:29379674

Determination of nanomolar chromate in drinking water with solid phase extraction and a portable spectrophotometer.

PubMed

Ma, Jian; Yang, Bo; Byrne, Robert H

2012-06-15

Determination of chromate at low concentration levels in drinking water is an important analytical objective for both human health and environmental science. Here we report the use of solid phase extraction (SPE) in combination with a custom-made portable light-emitting diode (LED) spectrophotometer to achieve detection of chromate in the field at nanomolar levels. The measurement chemistry is based on a highly selective reaction between 1,5-diphenylcarbazide (DPC) and chromate under acidic conditions. The Cr-DPC complex formed in the reaction can be extracted on a commercial C18 SPE cartridge. Concentrated Cr-DPC is subsequently eluted with methanol and detected by spectrophotometry. Optimization of analytical conditions involved investigation of reagent compositions and concentrations, eluent type, flow rate (sample loading), sample volume, and stability of the SPE cartridge. Under optimized conditions, detection limits are on the order of 3 nM. Only 50 mL of sample is required for an analysis, and total analysis time is around 10 min. The targeted analytical range of 0-500 nM can be easily extended by changing the sample volume. Compared to previous SPE-based spectrophotometric methods, this analytical procedure offers the benefits of improved sensitivity, reduced sample consumption, shorter analysis time, greater operational convenience, and lower cost. Copyright © 2012 Elsevier B.V. All rights reserved.

The Choroid Plexus of the Lateral Ventricle As the Origin of CSF Pulsation Is Questionable.

PubMed

Takizawa, Ken; Matsumae, Mitsunori; Hayashi, Naokazu; Hirayama, Akihiro; Sano, Fumiya; Yatsushiro, Satoshi; Kuroda, Kagayaki

2018-01-15

The advent of magnetic resonance imaging (MRI) enables noninvasive measurement of cerebrospinal fluid (CSF) motion, and new information about CSF motion has now been acquired. The driving force of the CSF has long been thought to be choroid plexus (CP) pulsation, but to investigate whether this phenomenon actually occurs, CSF motion was observed in the ventricular system and subarachnoid space using MRI. Eleven healthy volunteers, ranging in age from 23 to 58 years, participated in this study. The MRI sequences used were four-dimensional phase-contrast (4D-PC) and time-spatial labeling inversion pulse (t-SLIP). The 4D-PC images included sagittal images in the cranial midline, coronal images focusing on the foramen of Monro (FOM), and oblique coronal images of the trigone to quantify CSF velocity and acceleration. These values were compared and analyzed as non-parametric data using the Kolmogorov-Smirnov test and the Mann-Whitney U test. 4D-PC showed that the median CSF velocity was significantly lower in the posterior part of the lateral ventricle than in other regions. The quantitative analysis of velocity and acceleration showed that they were decreased around the CP in the trigone. Image analysis of both velocity mapping and t-SLIP showed suppressed CSF motion around the CP in the trigone. These findings cast doubt on CP pulsation being the driving force for CSF motion.

Household food insecurity and food expenditure in Bolivia, Burkina Faso, And the Philippines.

PubMed

Melgar-Quinonez, Hugo R; Zubieta, Ana C; MkNelly, Barbara; Nteziyaremye, Anastase; Gerardo, Maria Filipinas D; Dunford, Christopher

2006-05-01

This study examined the association between food insecurity, determined by a modified version of the U.S. Household Food Security Survey Module (US HFSSM), and total daily per capita (DPC) consumption (measured as household expenditures) in Bolivia, Burkina Faso, and the Philippines. Household food insecurity was determined by an adapted 9-item US HFSSM version. A short version of the World Bank's Living Standards Measurement Study (LSMS) consumption module measured household expenditures. Focus groups were used to adapt the survey instrument to each local context. The sample (n approximately 330 per country) includes residents of urban and rural areas. A 12-month food expenditure aggregate was generated as part of the total household expenditures calculation. DPC food expenditure, which represented over 60% of the total household consumption, as well as expenditures on specific food groups correlated with food insecurity both as a continuous Food Insecurity Score (FinSS) and a tricategorical food insecurity status variable. ANOVA and regression analysis were executed adjusting for social and demographic covariates. Food-secure households have significantly higher (P < 0.05) total DPC food expenditures as well as expenditures on animal source foods, vegetables, and fats and oils than moderately and severely food-insecure households. The results offer evidence that the US HFSSM is able to discriminate between households at different levels of food insecurity status in diverse developing world settings.

Selective sampling and measurement of Cr (VI) in water with polyquaternary ammonium salt as a binding agent in diffusive gradients in thin-films technique.

PubMed

Chen, Hong; Zhang, Yang-Yang; Zhong, Ke-Li; Guo, Lian-Wen; Gu, Jia-Li; Bo, Le; Zhang, Meng-Han; Li, Jian-Rong

2014-04-30

A diffusive gradients in thin films (DGT) device with polyquaternary ammonium salt (PQAS) as a novel binding agent (PQAS DGT) combined with graphite furnace atomic absorption spectrometry (GFAAS) was developed for the selective sampling and measurement of Cr (VI) in water. The performance of PQAS DGT was independent of pH 3-12 and ionic strength from 1 × 10(-3) to 1 molL(-1). DGT validation experiments showed that Cr (VI) was measured accurately as well as selectively by PQAS DGT, whereas Cr (III) was not determined quantitatively. Compared with diphenylcarbazide spectrophotometric method (DPC), the measurement of Cr (VI) with PQAS DGT was agreement with that of DPC method in the industrial wastewater. PQAS-DGT device had been successfully deployed in local freshwater. The concentrations of Cr (VI) determined by PQAS DGT coupled with GFAAS in Nuer River, Ling River and North Lake were 0.73 ± 0.09 μg L(-1), 0.50 ± 0.07 μg L(-1) and 0.61 ± 0.07 μg L(-1), respectively. The results indicate that PQAS DGT device can be used for the selective sampling and measurement Cr (VI) in water and its detection limit is lower than that of DPC method. Copyright © 2014 Elsevier B.V. All rights reserved.

Heart rate recovery improvement in patients following acute myocardial infarction: exercise training, β-blocker therapy or both.

PubMed

Medeiros, Wladimir M; de Luca, Fabio A; de Figueredo Júnior, Alcides R; Mendes, Felipe A R; Gun, Carlos

2018-05-01

Heart rate recovery (HRR) is a strong mortality predictor. Exercise training (ET) and β-blocker therapy have significant impact on the HRR of patients following myocardial infarction (MI). However, the combination of ET and β-blocker therapy, as well as its effectiveness in patients with a more compromised HRR (≤12 bpm), has been under-studied. Male patients (n = 64) post-MI were divided: Training + β-blocker (n = 19), Training (n = 15), β-blocker (n = 11) and Control (n = 19). Participants performed an ergometric test before and after 3 months of intervention. HRR was obtained during 5 min of recovery and corrected by the cardiac reserve (HRR corrCR ). Compared to pre-intervention, HRR corrCR was significantly increased during the 1st and 2nd minutes of recovery in the Training + β-blocker group (70·5% and 37·5%, respectively; P<0·05). A significant improvement, lasting from the 1st to the 4th minute of recovery, was also observed in the Training group (47%, 50%, 25% and 8·7%, respectively; P<0·05). In contrast, the β-blocker group showed a reduction in HRR corrCR during the 2nd and 3rd minutes of recovery (-21·2% and -16·3%, respectively; P<0·05). In addition, interventions involving ET (Training + βb, Training) were significantly more effective in patients with a pre-intervention HRR ≤ 12 bpm than for patients with HRR > 12 bpm. Combination of β-blocker therapy with ET does not compromise the effect of training and instead promotes HRR and aerobic capacity improvement. In addition, this combination is particularly beneficial for individuals presenting with a more compromised HRR. However, chronic administration of β-blocker therapy alone did not promote improvement in HRR or aerobic capacity. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Calcium channel blockers and transmitter release at the normal human neuromuscular junction.

PubMed

Protti, D A; Reisin, R; Mackinley, T A; Uchitel, O D

1996-05-01

Transmitter release evoked by nerve stimulation is highly dependent on Ca2+ entry through voltage-activated plasma membrane channels. Calcium influx may be modified in some neuromuscular diseases like Lambert-Eaton syndrome and amyotrophic lateral sclerosis. We studied the pharmacologic sensitivity of the transmitter release process to different calcium channel blockers in normal human muscles and found that funnel web toxin and omega-Agatoxin-IVA, both P-type calcium channel blockers, blocked nerve-elicited muscle action potentials and inhibited evoked synaptic transmission. The transmitter release was not affected either by nitrendipine, an L-type channel blocker, or omega-Conotoxin-GVIA, an N-type channel blocker. The pharmacologic profile of neuromuscular transmission observed in normal human muscles indicates that P-like channels mediate transmitter release at the motor nerve terminals.

Selenium carboxylic acids betaine; 3,3‧,3″-selenotris(propanoic acid) betaine, Se(CH2CH2COOH)2(CH2CH2COO)

NASA Astrophysics Data System (ADS)

Doudin, Khalid; Törnroos, Karl W.

2017-06-01

Attempts to prepare [Se(CH2CH2COOH)3]+Cl- from Se(CH2CH2COOH)2 and H2Cdbnd CHCOOH in concentrated hydrochloric acid, for the corresponding sulfonium salt, led exclusively to the Se-betaine, Se(CH2CH2COOH)2(CH2CH2COO). The Se-betaine crystallises in the space group P2l/c with the cell dimensions at 223 K, a = 5.5717(1), b = 24.6358(4), c = 8.4361(1) Å, β = 104.762(1)°, V = 1119.74(3) Å3, Z = 4, Dcalc = 1.763 Mgm- 3, μ = 3.364 Mm-1. The structure refined to RI = 0.0223 for 2801 reflections with Fo > 4σ(Fo). In the crystalline state the molecule is intermolecularly linked to neighbouring molecules by a number of hydrogen bonds; a very strong carboxylic-carboxylate bond with an O⋯O distance of 2.4435(16) Å, a medium strong carboxylic-carboxylate bond with an O⋯O distance of 2.6431(16) Å and several weak O⋯H(CH2) with O⋯C distances between 3.2 and 3.3 Å. In the carboxylic group involved in the very strong hydrogen bond the O⋯H bond is antiperiplanar to the Cdbnd O bond while the Osbnd H bond is periplanar to the Cdbnd O bond in the second carboxylic group. Based upon the Csbnd O bond lengths and the elongation of the Osbnd H bond involved in the strong hydrogen bond one may describe the compound as strongly linked units of Se(CH2CH2COOH)(CH2CH2COO)2 rather than Se(CH2CH2COOH)2(CH2CH2COO). The selenium atom forms two strong intramolecular 1,5-Se⋯O contacts, with a carboxylate oxygen atom, 2.9385(12) Å, and with a carboxylic oxygen atom, 2.8979(11) Å. To allow for these contacts the two organic fragments have been forced into the periplanar conformation. The molecule is only slightly asymmetric with regard to the Csbnd Sesbnd C bond angles but is very asymmetric with regard to the torsion angles.

Building thiol and metal-thiolate functions into coordination nets: Clues from a simple molecule

NASA Astrophysics Data System (ADS)

He, Jun; Yang, Chen; Xu, Zhengtao; Zeller, Matthias; Hunter, Allen D.; Lin, Jianhua

2009-07-01

The simple and easy-to-prepare bifunctional molecule 2,5-dimercapto-1,4-benzenedicarboxylic acid (H 4DMBD) interacts with the increasingly harder metal ions of Cu +, Pb 2+ and Eu 3+ to form the coordination networks of Cu 6(DMBD) 3(en) 4(Hen) 6 ( 1), Pb 2(DMBD)(en) 2 ( 2) and Eu 2(H 2DMBD) 3(DEF) 4 ( 3), where the carboxyl and thiol groups bind with distinct preference to the hard and soft metal ions, respectively. Notably, 1 features uncoordinated carboxylate groups and Cu 3 cluster units integrated via the thiolate groups into an extended network with significant interaction between the metal centers and the organic molecules; 2 features a 2D coordination net based on the mercapto and carboxylic groups all bonded to the Pb 2+ ions; 3 features free-standing thiol groups inside the channels of a metal-carboxylate-based network. This study illustrates the rich solid state structural features and potential functions offered by the carboxyl-thiol combination.

Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

PubMed

Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit

2015-09-01

Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

Associations between prescription copayment levels and β-blocker medication adherence in commercially insured heart failure patients 50 years and older.

PubMed

Patterson, Mark E; Blalock, Susan J; Smith, Andrew J; Murray, Michael D

2011-05-01

High prescription copayments may create barriers to care, resulting in medication nonadherence. Although many studies have examined these associations in commercially insured patients with chronic disease, few have examined β-blocker effects in heart failure patients. Associations between β-blocker prescription copayment levels and medication nonadherence were examined within commercially insured beneficiaries with a diagnosis of heart failure. Heart failure patients were identified as those with at least 1 inpatient claim or 2 outpatient claims with an associated International Classification of Diagnosis, 9th Edition (ICD-9) code of 428.x, in addition to those with at least 2 β-blocker claims. Copayment levels were defined in using $5.00 (USD) interval categories, and adherence was defined using the medication possession ratio (MPR). Ordinary least squares (OLS), fixed effects (FE), and random effect (RE) models were used to estimate associations between copayment level and MPR. Logistic regression was used to estimate the probability of nonadherence (MPR < 0.80) conditional upon copayment level. Regressions controlled for patient demographics, health status, prior hospitalizations, and concomitant medication use. The highest β-blocker copayment level ($26+) had an average MPR that was 0.07 (95% CI, -0.11 to -0.03), 0.08 (95% CI, -0.12 to -0.04), and 0.09 (95% CI, -0.17 to -0.02) units lower than β-blocker copayment level ($0 to $1) in the OLS, RE, and FE models, respectively. Copayment levels $21-$25 and $26+ were significantly associated with an increased risk of medication nonadherence (OR = 1.64; 95% CI, 1.1-2.4; and OR = 2.5; 95%, CI 1.6-4, respectively). Commercially insured heart failure patients aged ≥50 years who are prescribed higher costing β-blockers may have up to an average 9% decrease in annual β-blocker medication supply as well as an increased risk of nonadherence (MPR <0.80). Results need to be interpreted with caution given the potential of selection bias due to selective prescribing. Associations between copayment levels and nonadherence need to be further explored given the adverse health consequences of nonadherence to β-blockers. Copyright © 2011. Published by EM Inc USA.

Unravelling the surface chemistry of metal oxide nanocrystals, the role of acids and bases.

PubMed

De Roo, Jonathan; Van den Broeck, Freya; De Keukeleere, Katrien; Martins, José C; Van Driessche, Isabel; Hens, Zeger

2014-07-09

We synthesized HfO2 nanocrystals from HfCl4 using a surfactant-free solvothermal process in benzyl alcohol and found that the resulting nanocrystals could be transferred to nonpolar media using a mixture of carboxylic acids and amines. Using solution (1)H NMR, FTIR, and elemental analysis, we studied the details of the transfer reaction and the surface chemistry of the resulting sterically stabilized nanocrystals. As-synthesized nanocrystals are charge-stabilized by protons, with chloride acting as the counterion. Treatment with only carboxylic acids does not lead to any binding of ligands to the HfO2 surface. On the other hand, we find that the addition of amines provides the basic environment in which carboxylic acids can dissociate and replace chloride. This results in stable, aggregate-free dispersions of HfO2 nanocrystals, sterically stabilized by carboxylate ligands. Moreover, titrations with deuterated carboxylic acid show that the charge on the carboxylate ligands is balanced by coadsorbed protons. Hence, opposite from the X-type/nonstoichiometric nanocrystals picture prevailing in literature, one should look at HfO2/carboxylate nanocrystals as systems where carboxylic acids are dissociatively adsorbed to bind to the nanocrystals. Similar results were obtained with ZrO2 NCs. Since proton accommodation on the surface is most likely due to the high Brønsted basicity of oxygen, our model could be a more general picture for the surface chemistry of metal oxide nanocrystals with important consequences on the chemistry of ligand exchange reactions.

Spatial confinement effects on spectroscopic and morphological studies of nanosecond laser-ablated Zirconium

NASA Astrophysics Data System (ADS)

Hayat, Asma; Bashir, Shazia; Rafique, Muhammad Shahid; Ahmad, Riaz; Akram, Mahreen; Mahmood, Khaliq; Zaheer, Ali

2017-12-01

Spatial confinement effects on plasma parameters and surface morphology of laser ablated Zr (Zirconium) are studied by introducing a metallic blocker. Nd:YAG laser at various fluencies ranging from 8 J cm-2 to 32 J cm-2 was employed as an irradiation source. All measurements were performed in the presence of Ar under different pressures. Confinement effects offered by metallic blocker are investigated by placing the blocker at different distances of 6 mm, 8 mm and 10 mm from the target surface. It is revealed from LIBS analysis that both plasma parameters i.e. excitation temperature and electron number density increase with increasing laser fluence due to enhancement in energy deposition. It is also observed that spatial confinement offered by metallic blocker is responsible for the enhancement of both electron temperature and electron number density of Zr plasma. This is true for all laser fluences and pressures of Ar. Maximum values of electron temperature and electron number density without blocker are 12,600 K and 14 × 1017 cm-3 respectively whereas, these values are enhanced to 15,000 K and 21 × 1017 cm-3 in the presence of blocker. The physical mechanisms responsible for the enhancement of Zr plasma parameters are plasma compression, confinement and pronounced collisional excitations due to reflection of shock waves. Scanning Electron Microscope (SEM) analysis was performed to explore the surface morphology of laser ablated Zr. It reveals the formation of cones, cavities and ripples. These features become more distinct and well defined in the presence of blocker due to plasma confinement. The optimum combination of blocker distance, fluence and Ar pressure can identify the suitable conditions for defining the role of plasma parameters for surface structuring.

β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

PubMed

Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

2013-11-01

To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab. In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

A proto-Data Processing Center for LISA

NASA Astrophysics Data System (ADS)

Cavet, Cécile; Petiteau, Antoine; Le Jeune, Maude; Plagnol, Eric; Marin-Martholaz, Etienne; Bayle, Jean-Baptiste

2017-05-01

The LISA project preparation requires to study and define a new data analysis framework, capable of dealing with highly heterogeneous CPU needs and of exploiting the emergent information technologies. In this context, a prototype of the mission’s Data Processing Center (DPC) has been initiated. The DPC is designed to efficiently manage computing constraints and to offer a common infrastructure where the whole collaboration can contribute to development work. Several tools such as continuous integration (CI) have already been delivered to the collaboration and are presently used for simulations and performance studies. This article presents the progress made regarding this collaborative environment and discusses also the possible next steps towards an on-demand computing infrastructure. This activity is supported by CNES as part of the French contribution to LISA.

Synthesis of Sequence-Specific DNA-Protein Conjugates via a Reductive Amination Strategy

PubMed Central

Wickramaratne, Susith; Mukherjee, Shivam; Villalta, Peter W.; Schärer, Orlando D.; Tretyakova, Natalia

2013-01-01

DNA-protein cross-links (DPCs) are ubiquitous, structurally diverse DNA lesions formed upon exposure to bis-electrophiles, transition metals, UV light, and reactive oxygen species. Because of their super-bulky, helix distorting nature, DPCs interfere with DNA replication, transcription, and repair, potentially contributing to mutagenesis and carcinogenesis. However, the biological implications of DPC lesions have not been fully elucidated due to the difficulty of generating site-specific DNA substrates representative of DPC lesions formed in vivo. In the present study, a novel approach involving post-synthetic reductive amination has been developed to prepare a range of hydrolytically stable lesions structurally mimicking the DPCs produced between the N7 position of guanine in DNA and basic lysine or arginine side chains of proteins and peptides. PMID:23885807

6-Substituted 3,4-dihydro-naphthalene-2-carboxylic acids: synthesis and structure-activity studies in a novel class of human 5alpha reductase inhibitors.

PubMed

Baston, Eckhard; Salem, Ola I A; Hartmann, Rolf W

2002-10-01

Novel 3,4-dihydro-naphthalene-2-carboxylic acids were synthesized and evaluated for 5alpha reductase inhibitory activity. This enzyme exists in two isoforms and is a pharmacological target for the treatment of benign prostatic hyperplasia, male pattern baldness and acne. In the present study non-steroidal compounds capable of mimicking the transition state of the steroidal substrates were prepared. The synthetic strategy for the preparation of compounds 1-6 consisted of triflation followed by subsequent Heck-type carboxylation or methoxy carbonylation for 6-phenyl-3,4-dihydronaphthalen-2(1H)-one 1c. A Negishi-type coupling reaction between 6-(trifluoro-methanesulfonyloxy)-3,4-dihydro-naphthalene-2-carboxylic acid methyl ester 7b and various aryl bromides led, after further transformations, to 6-substituted 3,4-dihydro-naphthalene-2-carboxylic acids 7-15. In a similar way the corresponding naphthalene-2-carboxylic acids 16 and 17 were obtained. The DU 145 cell line and prostate homogenates served as enzyme sources for the human type 1 and type 2 isozymes, whereas ventral prostate was employed to evaluate rat isozyme inhibitory potency. The most active inhibitors identified in this study were 6-[4-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (3) (IC50 = 0.09 microM, rat type 1), 6-[3-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (13) (IC50 = 0.75 microM, human type 2; IC50 = 0.81 microM, human type 1) and 6-[4-(N,N-diisopropylamino-carbonyl)phenyl]naphthalene-2-carboxylic acid (16) (IC50 = 0.2 microM, human type 2). The latter compound was shown to deactivate the enzyme in an uncompetitive manner (Ki = 90 nM; Km, Testosterone = 0.8-1.0 microM) similar to the steroidal inhibitor Epristeride. Select inhibitors (13 and 16) were tested in vivo using testosterone propionate-treated, juvenile, orchiectomized SD-rats. None of the compounds was active at a dose of 25 mg/kg. This result might in part be ascribed to the relatively poor in vitro rat isozyme inhibitory potency.

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp; Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp; Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp

2014-07-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min formore » 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.« less

Syntheses, structures and magnetic properties of four coordination polymers based on nitrobenzene dicarboxylate and various N-donor coligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Gui-Lian; Yin, Wei-Dong; Liu, Guang-Zhen

Four new coordination polymers ([Ni(4-Nbdc)(bpa)(H{sub 2}O)]){sub n} (1), ([Co(4-Nbdc)(bpp) (H{sub 2}O)]){sub n} (2), ([Ni(4-Nbdc)(bpp)(H{sub 2}O)]·H{sub 2}O){sub n} (3), and ([Mn{sub 2}(3-Nbdc){sub 2}(bib){sub 3}]·2H{sub 2}O){sub n} (4) (4-Nbdc=4-nitrobenzene-1,2-dicarboxylate, 3-Nbdc=3-nitrobenzene-1,2-dicarboxylate, bpa=1,2-bi(4-pyridyl)ethane, bpp=1,3-bis(4-pyridyl)propane, and bib=1,4-bis(1-imidazoly)benzene), were synthesized by hydrothermal reactions, and characterized by single-crystal X-ray diffractions, elemental analysis, FT-IR, PXRD, TGA and magnetic analysis. Complexes 1 and 2 display quasi-trapezoidal chain and brick-wall layer, and both of them contain metal–carboxylate binuclear units. Complexes 3 and 4 exhibit three-dimensional frameworks with the (6{sup 6}) dia topology and (4{sup 4}.6{sup 10}.8)(4{sup 4}.6{sup 2}) fsc topology, and both of them contain metal–carboxylate chains. The carboxyl groupsmore » with syn-anti coordination mode mediate effectively the weak ferromagnetic coupling interaction within Ni(II)–carboxylate binuclear in 1 (J=1.27 cm{sup −1}) and Ni(II)–carboxylate chain in 3 (J=1.44 cm{sup −1}), respectively, and the carboxyl groups with anti-anti coordination mode leads to the classic antiferromagnetic coupling interaction within Mn(II)–carboxylate chain in 4 (J=−0.77 cm{sup −1}). - Highlights: • Four novel coordination polymers were hydrothermally synthesized. • 1 is 1D quasi-trapezoidal chain and 2 is brick-wall layer both with dinuclear units. • 3 and 4 show 3D frameworks both with 1D metal–carboxylate chains. • 1 and 3 exhibit ferromagnetic coupling, while 4 shows antiferromagnetic coupling.« less

Analysis of hydrophobic interactions of antagonists with the beta2-adrenergic receptor.

PubMed

Novoseletsky, V N; Pyrkov, T V; Efremov, R G

2010-01-01

The adrenergic receptors mediate a wide variety of physiological responses, including vasodilatation and vasoconstriction, heart rate modulation, and others. Beta-adrenergic antagonists ('beta-blockers') thus constitute a widely used class of drugs in cardiovascular medicine as well as in management of anxiety, migraine, and glaucoma. The importance of the hydrophobic effect has been evidenced for a wide range of beta-blocker properties. To better understand the role of the hydrophobic effect in recognition of beta-blockers by their receptor, we carried out a molecular docking study combined with an original approach to estimate receptor-ligand hydrophobic interactions. The proposed method is based on automatic detection of molecular fragments in ligands and the analysis of their interactions with receptors separately. A series of beta-blockers, based on phenylethanolamines and phenoxypropanolamines, were docked to the beta2-adrenoceptor binding site in the crystal structure. Hydrophobic complementarity between the ligand and the receptor was calculated using the PLATINUM web-server (http://model.nmr.ru/platinum). Based on the analysis of the hydrophobic match for molecular fragments of beta-blockers, we have developed a new scoring function which efficiently predicts dissociation constant (pKd) with strong correlations (r(2) approximately 0.8) with experimental data.

Organotin(IV) carboxylates based on 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetic acid: Syntheses, crystal structures, luminescent properties and antitumor activities

NASA Astrophysics Data System (ADS)

Xiao, Xiao; Liang, Jingwen; Xie, Jingyi; Liu, Xin; Zhu, Dongsheng; Dong, Yuan

2017-10-01

Organotin carboxylates based on an amide carboxylic acid 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetic acid (HL): [(Bn2Sn)2O2L]2·2C6H6 (1) (Bn = benzyl group) and (Ph2Sn)(L)2 (2) were synthesized and characterized by elemental analysis, IR, 1H, 13C, 119Sn NMR spectroscopy and X-ray crystallography diffraction analysis. Complex 1 is dimeric carboxylate tetraorganodistannoxane and show a "ladder-like" molecular structure. Complex 2 is a dialkyltin carboxylate monomer possessing crystallographically imposed two-fold symmetry. Ligand in 1 and 2 adopts unidentate and bidentate coordination respectively. Both 1 and 2 form 1D, 2D and 3D supramolecular organizations in the solid state mediated through Csbnd H⋯O and π⋯π interactions which are discussed in detail. The luminescent properties and preliminary antitumor activities about this series of complexes were also studied.

Crystal structure and magnetic properties of a unique 3D coordination polymer constructed from flexible aliphatic tricarballylic acid ligands featuring linear trimeric Manganese(II)-based, metal carboxylate chains

NASA Astrophysics Data System (ADS)

Zou, Hua-Hong; Zhang, Shu-Hua; Zeng, Ming-Hua; Zhou, Yan-Ling; Liang, Hong

2008-08-01

A novel linear trimeric-based, Mn(II)-carboxylate chain well separated by long-linking flexible aliphatic tricarballylic acid ligands in a 3D coordination polymer [Mn 3(C 6H 5O 6) 2(H 2O) 4] n ( 1, C 6H 5O 6dbnd CH (COO -)(CH 2COO -) 2, TCA) exhibits low-dimensional antiferromagnetic order at 3.0 K. Such magnetic behavior is arises from the alternate Antiferro-Antiferro-Antiferro' ( J1J1J2) repeating interactions sequence, based on the nature of the binding modes of Mn(II)-carboxylate chain and the effect of interchains arrangement of 1. The reported carboxylate-bridged metal chain systems display a new structurally authenticated example of linear homometallic spin arranged antiferromagnet among metal carboxylates.

The indirect detection of bleach (sodium hypochlorite) in beverages as evidence of product tampering.

PubMed

Jackson, David S; Crockett, David F; Wolnik, Karen A

2006-07-01

Bleach (sodium hypochlorite) has been identified as the adulterant in a relatively large number of product tamperings that have been investigated by the Forensic Chemistry Center (FCC) of the U.S. Food and Drug Administration. In this work, household bleach was added to 23 different beverages at each of three levels. The impact of sodium hypochlorite on these beverages over a 13-day study period was evaluated using the following techniques: diphenylamine spot test for oxidizing agents, potassium iodide-starch test paper for oxidizing agents, pH, iodometric titration for quantitating hypochlorite, ion chromatography for chloride and chlorate quantitation, automated headspace sampling with gas chromatography-flame ionization detection (GC-FID) for determination of chloroform, and visual and organoleptic observations. This study has shown that hypochlorite is fragile when added to most common beverages and typically breaks down either partially or completely over time. In cases where a beverage is suspected of being adulterated with bleach but tests for hypochlorite are negative, it is still possible to characterize the product to demonstrate that the results are consistent with the addition of bleach. An adulterated product will give a positive test for oxidizing agents using the diphenylamine spot test. It is likely that the pH of the adulterated product will be higher than a control of that product. Ion chromatographic analysis shows elevated chloride and chlorate as compared with a control. And, chloroform may also be detected by GC-FID especially if the beverage that was adulterated contains citric acid.

Resistance to neuraminidase inhibitors conferred by an R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population.

PubMed

Yen, H-L; McKimm-Breschkin, J L; Choy, K-T; Wong, D D Y; Cheung, P P H; Zhou, J; Ng, I H; Zhu, H; Webby, R J; Guan, Y; Webster, R G; Peiris, J S M

2013-07-16

We characterized the A/Shanghai/1/2013 virus isolated from the first confirmed human case of A/H7N9 disease in China. The A/Shanghai/1/2013 isolate contained a mixed population of R (65%; 15/23 clones) and K (35%; 8/23 clones) at neuraminidase (NA) residue 292, as determined by clonal sequencing. A/Shanghai/1/2013 with mixed R/K at residue 292 exhibited a phenotype that is sensitive to zanamivir and oseltamivir carboxylate by the enzyme-based NA inhibition assay. The plaque-purified A/Shanghai/1/2013 with dominant K292 (94%; 15/16 clones) showed sensitivity to zanamivir that had decreased by >30-fold and to oseltamivir carboxylate that had decreased by >100-fold compared to its plaque-purified wild-type counterpart possessing dominant R292 (93%, 14/15 clones). In Madin-Darby canine kidney (MDCK) cells, the plaque-purified A/Shanghai/1/2013-NAK292 virus exhibited no reduction in viral titer under conditions of increasing concentrations of oseltamivir carboxylate (range, 0 to 1,000 µM) whereas the replication of the plaque-purified A/Shanghai/1/2013-NAR292 and the A/Shanghai/2/2013 viruses was completely inhibited at 250 µM and 31.25 µM of oseltamivir carboxylate, respectively. Although the plaque-purified A/Shanghai/1/2013-NAK292 virus exhibited lower NA enzyme activity and a higher Km for 2'-(4-methylumbelliferryl)-α-d-N-acetylneuraminic acid than the wild-type A/Shanghai/1/2013-NAR292 virus, the A/Shanghai/1/2013-NAK292 virus formed large plaques and replicated efficiently in vitro. Our results confirmed that the NA R292K mutation confers resistance to oseltamivir, peramivir, and zanamivir in the novel human H7N9 viruses. Importantly, detection of the resistance phenotype may be masked in the clinical samples containing a mixed population of R/K at NA residue 292 in the enzyme-based NA inhibition assay. The neuraminidase (NA) inhibitors oseltamivir and zanamivir are currently the front-line therapeutic options against the novel H7N9 influenza viruses, which possess an S31N mutation that confers resistance to the M2 ion channel blockers. It is therefore important to evaluate the sensitivity of the clinical isolates to NA inhibitors and to monitor for the emergence of resistant variants. We characterized the A/Shanghai/1/2013 (H7N9) isolate which contained a mixed population of R/K at NA residue 292. While the clinical isolate exhibited a phenotype of sensitivity to NA inhibitors using the enzyme-based NA inhibition assay, the plaque-purified A/Shanghai/1/2013 virus with dominant K292 was resistant to zanamivir, peramivir, and oseltamivir. Resistance to NA inhibitors conferred by the R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population, and this should be taken into consideration while monitoring antiviral resistance in patients with H7N9 infection.

Vasopressin in reaggregated cell cultures of the developing hypothalamus.

PubMed

Notter, M F; Gash, D M; Sladek, C D; Scharoun, S L

1984-03-01

A microsystem for rotation-mediated aggregate cell culture studies has been devised to examine vasopressin (VP) biosynthesis of developing rat hypothalamus. Trypsin-dispersed hypothalamic tissue was placed into 24 well tissue culture dishes and VP content of culture medium and cells was measured over time by a radioimmunoassay. Reaggregates formed within 4 hr when rotated at 70 rpm in a humid CO2 incubator. Nineteen days post coitus (dpc) hypothalamic reaggregates had 336 pg VP/10(6) cells while the medium showed 260 pg VP/ml after four days. Measurable VP was seen in fetal tissue after ten days while comparable amounts of VP were present in one day neonatal hypothalamus over this same period. Morphological examination of reaggregates indicated the presence of viable cells throughout the cell mass after ten days of culture. Co-cultivation studies with dispersed posterior pituitary indicated that reaggregates from one day neonate hypothalamus had significantly increased VP levels when co-cultured with one day neonatal posterior pituitary; however, this effect was not seen with 19 dpc co-cultures. These data demonstrate that development of neurosecretory activity of discrete regions of the hypothalamus can be examined early in vitro in a reaggregate cell culture system.

Specific extraction of chromium as tetrabutylammonium-chromate and spectrophotometric determination by diphenylcarbazide: speciation of chromium in effluent streams.

PubMed

Noroozifar, M; Khorasani-Motlagh, M

2003-05-01

A very specific, selective, simple, and inexpensive procedure was developed for the speciation of CrVI and CrIII. This method is based on the quantitative extraction of chromate and CrIII (previously oxidized to CrVI) as a tetrabutylammonium-chromate ion-pair in methyl isobutyl ketone (MIBK), and then back extraction and preconcentration with an acidic diphenylcarbazide (DPC) solution. Back extraction was applied to achieve further preconcentration by a final factor of 20. The CrVI-DPC complex was determined in back-extract by a spectrophotometer at 548 nm. Under these extraction conditions, most of the probable concomitant cations and anions remained in the first inorganic phase. The calibration curve was linear up to 0.14 microg L(-1) of CrVI with a detection limit of 2.22 ng L(-1). The developed procedure was found to be suitable for the determination of the CrVI and CrIII species in various natural water samples with a relative standard deviation of better than 1.6%. The method was successfully applied to the speciation of chromium in spiked natural water samples, and also samples of effluent from a leather treatment plant.

[Results of an intervention to reduce potentially inappropriate prescriptions of beta blockers and calcium channel blockers].

PubMed

Machado-Alba, J E; Giraldo-Giraldo, C; Aguirre Novoa, A

2016-01-01

To determine the frequency of simultaneous prescription of β-blockers and calcium channel blockers, notify the cardiovascular risk of these patients to the health care professionals in charge of them, and achieve a reduction in the number of those who use them. Quasi-experimental, prospective study by developing an intervention on medical prescriptions of patients older than 65 years treated between January 1 and July 30, 2014, affiliated to the Health System in 101 cities in Colombia. A total of 43,180 patients received a β-blocker each month, and 14,560 receiving a calcium channel blocker were identified. Educational interventions were performed and an evaluation was made, using sociodemographic and pharmacological variables, on the number of patients that stopped taking any of the two drugs in the following three months. A total of 535 patients, with a mean age 75.8±6.7 years received concomitant β-blockers plus calcium channel blockers. Modification of therapy was achieved in 235 patients (43.9% of users) after 66 educational interventions. In 209 cases (88.9%) one of the two drugs was suspended, and 11.1% changed to other antihypertensive drugs. The variable of being more than 85 years old (OR: 1.93; 95% CI: 1.07-3.50), and receiving concomitant medication with inhibitors of the renin-angiotensin system (OR: 2.16; 95% CI: 1.28-3.65) were associated with increased risk of their doctor changing or stopping the prescription. An improved adherence to recommendations for appropriate use of β-blockers and calcium channel blockers by health service providers was achieved. Intervention programs that reduce potentially inappropriate prescriptions for patients treated for cardiovascular disease should be used more frequently. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

Hydrothermal syntheses, characterizations and crystal structures of a new lead(II) carboxylate-phosphonate with a double layer structure and a new nickel(II) carboxylate-phosphonate containing a hydrogen-bonded 2D layer with intercalation of ethylenediamines

NASA Astrophysics Data System (ADS)

Song, Jun-Ling; Mao, Jiang-Gao; Sun, Yan-Qiong; Zeng, Hui-Yi; Kremer, Reinhard K.; Clearfield, Abraham

2004-03-01

Hydrothermal reactions of N, N-bis(phosphonomethyl)aminoacetic acid (HO 2CCH 2N(CH 2PO 3H 2) 2) with metal(II) salts afforded two new metal carboxylate-phosphonates, namely, Pb 2[O 2CCH 2N(CH 2PO 3)(CH 2PO 3H)]·H 2O ( 1) and {NH 3CH 2CH 2NH 3}{Ni[O 2CCH 2N(CH 2PO 3H) 2](H 2O) 2} 2 ( 2). Among two unique lead(II) ions in the asymmetric unit of complex 1, one is five coordinated by five phosphonate oxygen atoms from 5 ligands, whereas the other one is five-coordinated by a tridentate chelating ligand (1 N and 2 phosphonate O atoms) and two phosphonate oxygen atoms from two other ligands. The carboxylate group of the ligand remains non-coordinated. The bridging of above two types of lead(II) ions through phosphonate groups resulted in a <002> double layer with the carboxylate group of the ligand as a pendant group. These double layers are further interlinked via hydrogen bonds between the carboxylate groups into a 3D network. The nickel(II) ion in complex 2 is octahedrally coordinated by a tetradentate chelating ligand (two phosphonate oxygen atoms, one nitrogen and one carboxylate oxygen atoms) and two aqua ligands. These {Ni[O 2CCH 2N(CH 2PO 3H) 2][H 2O] 2} - anions are further interlinked via hydrogen bonds between non-coordinated phosphonate oxygen atoms to form a <800> hydrogen bonded 2D layer. The 2H-protonated ethylenediamine cations are intercalated between two layers, forming hydrogen bonds with the non-coordinated carboxylate oxygen atoms. Results of magnetic measurements for complex 2 indicate that there is weak Curie-Weiss behavior with θ=-4.4 K indicating predominant antiferromagnetic interaction between the Ni(II) ions. Indication for magnetic low-dimension magnetism could not be detected.

Rapid determination of chromium(VI) in electroplating waste water by use of a spectrophotometric flow injection system.

PubMed

Yuan, Dong; Fu, Dayou; Wang, Rong; Yuan, Jigang

2008-11-01

A new rapid and sensitive FI method is reported for spectrophotometric determination of trace chromium(VI) in electroplating waste water. The method is based on the reaction of Cr(VI) with sodium diphenylamine sulfonate (DPH) in acidic medium to form a purple complex (lambda(max) = 550 nm). Under the optimized conditions, the calibration curve is linear in the range 0.04-3.8 microg ml(-1) at a sampling rate of 30 h(-1). The detection limit of the method is 0.0217 microg ml(-1), and the relative standard deviation is 1.1% for eight determinations of 2 microg ml(-1) Cr(VI). The proposed method was applied to the determination of chromium in electroplating waste water with satisfactory results.

Synthesis and structures of cadmium carboxylate and thiocarboxylate compounds with a sulfur-rich coordination environment: Carboxylate exchange kinetics involving tris(2-mercapto-1- t-butylimidazolyl)hydroborato cadmium complexes, [Tm But]Cd(O 2CR)

DOE PAGES

Kreider-Mueller, Ava; Quinlivan, Patrick J.; Owen, Jonathan S.; ...

2015-03-31

Here, a series of cadmium carboxylate compounds in a sulfur-rich environment provided by the tris(2- tert-butylmercaptoimidazolyl)hydroborato ligand, namely, [Tm But]CdO 2CR, has been synthesized via the reactions of the cadmium methyl derivative [Tm But]CdMe with RCO 2H. Such compounds mimic aspects of cadmium-substituted zinc enzymes and also the surface atoms of cadmium chalcogenide crystals, and have therefore been employed to model relevant ligand exchange processes. Significantly, both 1H and 19F NMR spectroscopy demonstrate that the exchange of carboxylate groups between [Tm But]Cd(κ 2-O 2CR) and the carboxylic acid RCO 2H is facile on the NMR time scale, even at lowmore » temperature. Analysis of the rate of exchange as a function of concentration of RCO 2H indicates that reaction occurs via an associative rather than dissociative pathway. In addition to carboxylate compounds, the thiocarboxylate derivative [Tm But]Cd[κ 1-SC(O)Ph] has also been synthesized via the reaction of [Tm But]CdMe with thiobenzoic acid. The molecular structure of [Tm But]Cd[κ 1-SC(O)Ph] has been determined by X-ray diffraction, and an interesting feature is that, in contrast to the carboxylate derivatives [Tm But]Cd(κ 2-O 2CR), the thiocarboxylate ligand binds in a κ 1 manner via only the sulfur atom.« less

Synthesis and structures of cadmium carboxylate and thiocarboxylate compounds with a sulfur-rich coordination environment: Carboxylate exchange kinetics involving tris(2-mercapto-1- t-butylimidazolyl)hydroborato cadmium complexes, [Tm But]Cd(O 2CR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreider-Mueller, Ava; Quinlivan, Patrick J.; Owen, Jonathan S.

Here, a series of cadmium carboxylate compounds in a sulfur-rich environment provided by the tris(2- tert-butylmercaptoimidazolyl)hydroborato ligand, namely, [Tm But]CdO 2CR, has been synthesized via the reactions of the cadmium methyl derivative [Tm But]CdMe with RCO 2H. Such compounds mimic aspects of cadmium-substituted zinc enzymes and also the surface atoms of cadmium chalcogenide crystals, and have therefore been employed to model relevant ligand exchange processes. Significantly, both 1H and 19F NMR spectroscopy demonstrate that the exchange of carboxylate groups between [Tm But]Cd(κ 2-O 2CR) and the carboxylic acid RCO 2H is facile on the NMR time scale, even at lowmore » temperature. Analysis of the rate of exchange as a function of concentration of RCO 2H indicates that reaction occurs via an associative rather than dissociative pathway. In addition to carboxylate compounds, the thiocarboxylate derivative [Tm But]Cd[κ 1-SC(O)Ph] has also been synthesized via the reaction of [Tm But]CdMe with thiobenzoic acid. The molecular structure of [Tm But]Cd[κ 1-SC(O)Ph] has been determined by X-ray diffraction, and an interesting feature is that, in contrast to the carboxylate derivatives [Tm But]Cd(κ 2-O 2CR), the thiocarboxylate ligand binds in a κ 1 manner via only the sulfur atom.« less

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

2012-10-01

Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P < 0.001), -9.7 (95% CI -14.2 to -5.3; P < 0.001) and -1.7 (95% CI -3.2 to -0.2; P= 0.032) respectively, while α-blockers plus antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P < 0.001). • With respect to responder analysis compared with placebo, anti-inflammatories showed the greatest response rates (risk ratio 1.7, 95% CI 1.4-2.1; P < 0.001) followed by α-blockers (risk ratio 1.4, 95% CI 1.1-1.8; P= 0.013) and antibiotics (risk ratio 1.2, 95% CI 0.7-1.9; P= 0.527). α-blockers, antibiotics and/or anti-inflammatory/immune modulation therapy appear to be beneficial for some patients with CP/CPPS. • The magnitude of effect and the disconnect between mean CPSI decrease and response rates compared with placebo suggest that directed multimodal therapy, rather than mono-therapy, with these agents should be considered for optimal management of CP/CPPS. © 2012 BJU INTERNATIONAL.

Influence of process conditions on carboxylation of higher alkylphenols by Kolbe-Schmidt reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordash, Yu.T.; Voloshin, N.L.; Prusak, A.G.

1987-01-01

The authors present experimental data on the carboxylation of higher alkylphenols prepared by alkylating phenol with a 240-320/sup 0/C alpha-olefin cut obtained by thermal cracking of the paraffins, on KU-2 catalyst. Experiments were performed to determine the influence of temperature and pressure on the conversion of sodium alkylphenolate to alkylsalicylate. The content of alkylphenols in the carboxylated products was demonstrated by solubilizing the carboxylate in water, subsequently centrifuging the water-organic mixture that was obtained. From the data presented here, it follows that in the carboxylation of sodium alkylphenolate, side reactions can be minimized if the process is performed at 130-135/supmore » 0/C with a CO/sub 2/ pressure no lower than 2 MPa.« less

Azilsartan and its Zn(II) complex. Synthesis, anticancer mechanisms of action and binding to bovine serum albumin.

PubMed

Martínez, Valeria R; Aguirre, María V; Todaro, Juan S; Piro, Oscar E; Echeverría, Gustavo A; Ferrer, Evelina G; Williams, Patricia A M

2018-04-01

Azilsartan is the eighth approved member of angiotensin II receptor blockers for hypertension treatment. Considering that some drugs have additional effects when administered, we studied its effects and mechanisms of action on a human lung cancer cell line A549. We have also modified the structure of the drug by complexation with Zn(II) cation and assayed the anticancer effect. The crystal structure of the new binuclear Zn(II) complex, for short [Zn 2 (azil) 2 (H 2 O) 4 ]·2H 2 O (ZnAzil), was determined by X-ray diffraction methods. The zinc ions are bridged by azilsartan ligands through their carboxylate oxygen and oxadiazol nitrogen atoms. The compounds were examined for their cytotoxic effects against human lung fibroblast (MRC5) and human lung cancer (A549) cell lines. Azilsartan displayed low cytotoxic effects at 150 μM concentrations in A549 human lung cancer cells but the higher effect measured for the Zn complex suggested that this compound may act as an anticancer agent. An apoptotic oxidative stress mechanism of action via the mitochondrial-dependent intrinsic pathway has been determined. Besides, the compounds exerted weak cytotoxic effects in the normal lung related cell line MRC5. Binding constants of the complex formed between each compound and bovine serum albumin (BSA) are in the intermediate range, hence suggesting that azilsartan and ZnAzil could be bonded and transported by BSA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Degradation of pharmaceutical beta-blockers by electrochemical advanced oxidation processes using a flow plant with a solar compound parabolic collector.

PubMed

Isarain-Chávez, Eloy; Rodríguez, Rosa María; Cabot, Pere Lluís; Centellas, Francesc; Arias, Conchita; Garrido, José Antonio; Brillas, Enric

2011-08-01

The degradation of the beta-blockers atenolol, metoprolol tartrate and propranolol hydrochloride was studied by electro-Fenton (EF) and solar photoelectro-Fenton (SPEF). Solutions of 10 L of 100 mg L⁻¹ of total organic carbon of each drug in 0.1 M Na₂SO₄ with 0.5 mM Fe²⁺ of pH 3.0 were treated in a recirculation flow plant with an electrochemical reactor coupled with a solar compound parabolic collector. Single Pt/carbon felt (CF) and boron-doped diamond (BDD)/air-diffusion electrode (ADE) cells and combined Pt/ADE-Pt/CF and BDD/ADE-Pt/CF cells were used. SPEF treatments were more potent with the latter cell, yielding 95-97% mineralization with 100% of maximum current efficiency and energy consumptions of about 0.250 kWh g TOC⁻¹. However, the Pt/ADE-Pt/CF cell gave much lower energy consumptions of about 0.080 kWh g TOC⁻¹ with slightly lower mineralization of 88-93%, then being more useful for its possible application at industrial level. The EF method led to a poorer mineralization and was more potent using the combined cells by the additional production of hydroxyl radicals (•OH) from Fenton's reaction from the fast Fe²⁺ regeneration at the CF cathode. Organics were also more rapidly destroyed at BDD than at Pt anode. The decay kinetics of beta-blockers always followed a pseudo first-order reaction, although in SPEF, it was accelerated by the additional production of •OH from the action of UV light of solar irradiation. Aromatic intermediates were also destroyed by hydroxyl radicals. Ultimate carboxylic acids like oxalic and oxamic remained in the treated solutions by EF, but their Fe(III) complexes were photolyzed by solar irradiation in SPEF, thus explaining its higher oxidation power. NO₃⁻ was the predominant inorganic ion lost in EF, whereas the SPEF process favored the production of NH₄⁺ ion and volatile N-derivatives. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative Efficacy of Tongxinluo Capsule and Beta-Blockers in Treating Angina Pectoris: Meta-Analysis of Randomized Controlled Trials.

PubMed

Jia, Yongliang; Leung, Siu-wai

2015-11-01

There have been no systematic reviews, let alone meta-analyses, of randomized controlled trials (RCTs) comparing tongxinluo capsule (TXL) and beta-blockers in treating angina pectoris. This study aimed to evaluate the efficacy of TXL and beta-blockers in treating angina pectoris by a meta-analysis of eligible RCTs. The RCTs comparing TXL with beta-blockers (including metoprolol) in treating angina pectoris were searched and retrieved from databases including PubMed, Chinese National Knowledge Infrastructure, and WanFang Data. Eligible RCTs were selected according to prespecified criteria. Meta-analysis was performed on the odds ratios (OR) of symptomatic and electrocardiographic (ECG) improvements after treatment. Subgroup analysis, sensitivity analysis, meta-regression, and publication biases analysis were conducted to evaluate the robustness of the results. Seventy-three RCTs published between 2000 and 2014 with 7424 participants were eligible. Overall ORs comparing TXL with beta-blockers were 3.40 (95% confidence interval [CI], 2.97-3.89; p<0.0001) for symptomatic improvement and 2.63 (95% CI, 2.29-3.02; p<0.0001) for ECG improvement. Subgroup analysis and sensitivity analysis found no statistically significant dependence of overall ORs on specific study characteristics except efficacy criteria. Meta-regression found no significant except sample sizes for data on symptomatic improvement. Publication biases were statistically significant. TXL seems to be more effective than beta-blockers in treating angina pectoris, on the basis of the eligible RCTs. Further RCTs are warranted to reduce publication bias and verify efficacy.

Cancer-associated Isocitrate Dehydrogenase Mutations Inactivate NADPH-dependent Reductive Carboxylation*

PubMed Central

Leonardi, Roberta; Subramanian, Chitra; Jackowski, Suzanne; Rock, Charles O.

2012-01-01

Isocitrate dehydrogenase (IDH) is a reversible enzyme that catalyzes the NADP+-dependent oxidative decarboxylation of isocitrate (ICT) to α-ketoglutarate (αKG) and the NADPH/CO2-dependent reductive carboxylation of αKG to ICT. Reductive carboxylation by IDH1 was potently inhibited by NADP+ and, to a lesser extent, by ICT. IDH1 and IDH2 with cancer-associated mutations at the active site arginines were unable to carry out the reductive carboxylation of αKG. These mutants were also defective in ICT decarboxylation and converted αKG to 2-hydroxyglutarate using NADPH. These mutant proteins were thus defective in both of the normal reactions of IDH. Biochemical analysis of heterodimers between wild-type and mutant IDH1 subunits showed that the mutant subunit did not inactivate reductive carboxylation by the wild-type subunit. Cells expressing the mutant IDH are thus deficient in their capacity for reductive carboxylation and may be compromised in their ability to produce acetyl-CoA under hypoxia or when mitochondrial function is otherwise impaired. PMID:22442146

Venous pump of the calf: a study of venous and muscular pressures.

PubMed

Alimi, Y S; Barthelemy, P; Juhan, C

1994-11-01

Little data are available concerning the relation between the muscular pumping mechanism and the variation of superficial and deep venous pressure during normal action of the calf pump; therefore we undertook this study to determine the pressure values in three compartments of the calf and in the deep and the superficial venous system and to establish correlation between muscular and venous pressure. Nine healthy young women with a mean age of 23 years (range 19 to 28 years) were examined. In the same calf, a muscular catheter was placed in the deep posterior compartment (DPC), in the superficial posterior compartment (SPC), and in the anterior tibial compartment (ATC), and a vascular catheter was placed in the popliteal vein and in the greater saphenous vein (GSV). The five lines of pressure were simultaneously recorded in the following situations: at rest, during Valsalva maneuver, foot flexion, and foot extension. The situation was studied with the patient in the following positions: decubitus, sitting, standing, and squatting. A final continuous recording was carried out after the patient had been walking for 5 minutes. Mean values with standard errors of muscular and venous pressure were established in each situation. At rest and during Valsalva maneuver, the muscular pressures did not vary, whereas venous pressures increased significantly when the patient was sitting and standing. On the other hand, squatting was associated with a rise in the muscular and vein pressures. Foot flexion entailed a significant increase in the ATC pressure and a rise in the GSV pressure, whereas foot extension caused the DPC pressure to rise without venous pressure modifications. Walking was associated with an alternating increase in the DPC, SPC, GSV and popliteal vein pressures when the foot was compressed to floor followed by a significant decrease when the foot pressure was released. The variations in the deep and superficial venous pressures when the patient is sitting and standing both at rest and during Valsalva maneuver are not associated with an increase in the muscular pressure. On the contrary, during foot movements, the ATC and the DPC are responsible for superficial vein pressure variations without modifications of the SPC pressure.

Crystal structure of [NaZn(BTC)(H2O)4]·1.5H2O (BTC = benzene-1,3,5-tri-carb-oxy-l-ate): a heterometallic coordination compound.

PubMed

Ni, Min; Li, Quanle; Chen, Hao; Li, Shengqing

2015-07-01

The title coordination polymer, poly[[μ-aqua-tri-aqua-(μ3-benzene-1,3,5-tri-carboxyl-ato)sodiumzinc] sesquihydrate], {[NaZn(C9H3O6)(H2O)4]·1.5H2O} n , was obtained in ionic liquid microemulsion at room temperture by the reaction of benzene-1,3,5-tri-carb-oxy-lic acid (H3BTC) with Zn(NO3)2·6H2O in the presence of NaOH. The asymmetric unit comprises two Na(+) ions (each located on an inversion centre), one Zn(2+) ion, one BTC ligand, four coordinating water mol-ecules and two solvent water molecules, one of which is disordered about an inversion centre and shows half-occupation. The Zn(2+) cation is five-coordinated by two carboxyl-ate O atoms from two different BTC ligands and three coordinating H2O mol-ecules; the Zn-O bond lengths are in the range 1.975 (2)-2.058 (3) Å. The Na(+) cations are six-coordinated but have different arrangements of the ligands: one is bound to two carboxyl-ate O atoms of two BTC ligands and four O atoms from four coordinating H2O mol-ecules while the other is bound by four carboxyl-ate O atoms from four BTC linkers and two O atoms of coordinating H2O mol-ecules. The completely deprotonated BTC ligand acts as a bridging ligand binding the Zn(2+) atom and Na(+) ions, forming a layered structure extending parallel to (100). An intricate network of O-H⋯O hydrogen bonds is present within and between the layers.

Regioselective Ni-Catalyzed Carboxylation of Allylic and Propargylic Alcohols with Carbon Dioxide.

PubMed

Chen, Yue-Gang; Shuai, Bin; Ma, Cong; Zhang, Xiu-Jie; Fang, Ping; Mei, Tian-Sheng

2017-06-02

An efficient Ni-catalyzed reductive carboxylation of allylic alcohols with CO 2 has been successfully developed, providing linear β,γ-unsaturated carboxylic acids as the sole regioisomer with generally high E/Z stereoselectivity. In addition, the carboxylic acids can be generated from propargylic alcohols via hydrogenation to give allylic alcohol intermediates, followed by carboxylation. A preliminary mechanistic investigation suggests that the hydrogenation step is made possible by a Ni hydride intermediate produced by a hydrogen atom transfer from water.

Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis.

PubMed

Ventre, Sandrine; Petronijevic, Filip R; MacMillan, David W C

2015-05-06

The direct conversion of aliphatic carboxylic acids to the corresponding alkyl fluorides has been achieved via visible light-promoted photoredox catalysis. This operationally simple, redox-neutral fluorination method is amenable to a wide variety of carboxylic acids. Photon-induced oxidation of carboxylates leads to the formation of carboxyl radicals, which upon rapid CO2-extrusion and F(•) transfer from a fluorinating reagent yield the desired fluoroalkanes with high efficiency. Experimental evidence indicates that an oxidative quenching pathway is operable in this broadly applicable fluorination protocol.

Synthesis and biological evaluation of naphthyldesferrithiocin iron chelators.

PubMed

Bergeron, R J; Wiegand, J; Wollenweber, M; McManis, J S; Algee, S E; Ratliff-Thompson, K

1996-04-12

The synthesis and iron-clearing properties of the naphthyldesferrithiocins 2-(2'-hydroxynaphth-1'-yl)-delta2-thiazoline-(4R)-carboxylic acid, 2-(2'-hydroxynaphth-1'-yl)-delta2-thiazoline-(4S)-carboxylic acid, 2-(3'-hydroxynaphth-2'-yl)-delta2-thiazoline-(4R)-carboxylic acid, and 2-(3'-hydroxynaphth-2'-yl)-delta2-thiazoline-(4S)-carboxylic acid are described. While the bile duct-cannulated rat model clearly demonstrates that the 3'-hydroxynaphthyl-2'-yl compounds are orally active iron-clearing agents and the corresponding 2'-hydroxynaphthyl-1'-yl compounds are not, in the primate model none of the benz-fused desazadesferrithiocin analogues are active. Oral versus subcutaneous administration of these ligands strongly suggests that metabolism is a key issue in their iron-clearing properties and that these benz-fused desferrithiocins are not good candidates for orally active iron-clearing drugs.

Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase.

PubMed

Wang, Min; Gao, Mingzhang; Zheng, Qi-Huang

2014-08-15

The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [(11)C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10a) and [(11)C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10b) were prepared from their corresponding precursors with [(11)C]CH3OTf under basic condition through O-[(11)C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS). Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis by metadynamics simulation of binding pathway of influenza virus M2 channel blockers.

PubMed

Sakai, Yuri; Kawaguchi, Atsushi; Nagata, Kyosuke; Hirokawa, Takatsugu

2018-01-01

M2 protein of influenza A virus is a proton channel spanning the viral envelope. Activity of this proton channel is required for uncoating of viral particles and equilibrating the pH across the trans Golgi apparatus, which prevents conformational change in hemagglutinin. Amantadine, an anti-influenza A virus drug, inhibits M2 proton channel activity by binding to the channel pore; however, most currently circulating influenza A viruses are amantadine-resistant. The most prevalent resistant mutation is a substitution from Ser31 to Asn31 in M2. Further atomistic analysis of ligand-M2 complexes is needed to provide new approaches for the design of novel M2 channel blockers. Here, the free energy profiles of the binding kinetics of M2 channel blockers were examined by well-tempered metadynamics simulations and it was found that amantadine first binds to Asp24 of S31 M2 and forms a metastable conformation. In contrast, the free energy profiles of adamantyl bromothiophene dual inhibitor with either S31 M2 or N31 M2 are broad funnel-shaped curves, suggesting that adamantyl bromothiophene does not form metastable complexes with M2. The trajectory of well-tempered metadynamics simulations revealed that steric hindrance between adamantyl bromothiophene and S31 M2 interrupts formation of a metastable conformation at Asp24 and that a halogen bond between the bromine atom and N31 is responsible for pulling down the ligand to the channel pore of N31 M2 in the absence of a metastable state. Binding pathways of M2 channel blockers to M2 are here proposed on the basis of these findings; they may provide new approaches to designing further M2 channel blockers. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

A copper(II) paddle-wheel structure of tranexamic acid: di-chloro-tetra-kis-[μ-4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ato-O,O']dicopper(II) dichloride hexa-hydrate.

PubMed

Altaf, Muhammad; Stoeckli-Evans, Helen

2017-10-01

Tranexamic acid [systematic name: trans -4-(amino-meth-yl)cyclo-hexane-1-carb-oxy-lic acid], is an anti-fibrinolytic amino acid that exists as a zwitterion [ trans -4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ate] in the solid state. Its reaction with copper chloride leads to the formation of a compound with a copper(II) paddle-wheel structure that crystallizes as a hexa-hydrate, [Cu 2 Cl 2 (C 8 H 15 NO 2 ) 4 ] 2+ ·2Cl - ·6H 2 O. The asymmetric unit is composed of a copper(II) cation, two zwitterionic tranexamic acid units, a coordinating Cl - anion and a free Cl - anion, together with three water mol-ecules of crystallization. The whole structure is generated by inversion symmetry, with the Cu⋯Cu axle of the paddle-wheel dication being located about a center of symmetry. The cyclo-hexane rings of the zwitterionic tranexamic acid units have chair conformations. The carboxyl-ate groups that bridge the two copper(II) cations are inclined to one another by 88.4 (8)°. The copper(II) cation is ligated by four carboxyl-ate O atoms in the equatorial plane and by a Cl - ion in the axial position. Hence, it has a fivefold O 4 Cl coordination sphere with a perfect square-pyramidal geometry and a τ 5 index of zero. In the crystal, the paddle-wheel dications are linked by a series of N-H⋯Cl hydrogen bonds, involving the coordinating and free Cl - ions, forming a three-dimensional network. This network is strengthened by a series of N-H⋯O water , O water -H⋯Cl and O water -H⋯O hydrogen bonds.

A stereospecific carboxyl esterase from Bacillus coagulans hosting nonlipase activity within a lipase-like fold.

PubMed

De Vitis, Valerio; Nakhnoukh, Cristina; Pinto, Andrea; Contente, Martina L; Barbiroli, Alberto; Milani, Mario; Bolognesi, Martino; Molinari, Francesco; Gourlay, Louise J; Romano, Diego

2018-03-01

Microbial carboxylesterases are important biocatalysts that selectively hydrolyze an extensive range of esters. Here, we report the biochemical and structural characterization of an atypical carboxylesterase from Bacillus coagulans (BCE), endowed with high enantioselectivity toward different 1,2-O-isopropylideneglycerol (IPG or solketal) esters. BCE efficiently catalyzes the production of enantiopure (S)-IPG, a chiral building block for the synthesis of β-blockers, glycerophospholipids, and prostaglandins; efficient hydrolysis was observed up to 65 °C. To gain insight into the mechanistic bases of such enantioselectivity, we solved the crystal structures of BCE in apo- and glycerol-bound forms at resolutions of 1.9 and 1.8 Å, respectively. In silico docking studies on the BCE structure confirmed that IPG esters with small acyl chains (≤ C6) were easily accommodated in the active site pocket, indicating that small conformational changes are necessary to accept longer substrates. Furthermore, docking studies suggested that enantioselectivity may be due to an improved stabilization of the tetrahedral reaction intermediate for the S-enantiomer. Contrary to the above functional data implying nonlipolytic functions, BCE displays a lipase-like 3D structure that hosts a "lid" domain capping the main entrance to the active site. In lipases the lid mediates catalysis through interfacial activation, a process that we did not observe for BCE. Overall, we present the functional-structural properties of an atypical carboxyl esterase that has nonlipase-like functions, yet possesses a lipase-like 3D fold. Our data provide original enzymatic information in view of BCE applications as an inexpensive, efficient biocatalyst for the production of enantiopure (S)-IPG. Coordinates and structure factors have been deposited in the Protein Data Bank (www.rcsb.org) under accession numbers 5O7G (apo-BCE) and 5OLU (glycerol-bound BCE). © 2017 Federation of European Biochemical Societies.

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

PubMed Central

Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

2009-01-01

Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia.

PubMed

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Maeda, Ayumi; Fischer, Michael A; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-09-01

β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries. We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications. There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively). Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia. Copyright © 2016 by the American Academy of Pediatrics.

Aqueous infrared carboxylate absorbances: Aliphatic di-acids

USGS Publications Warehouse

Cabaniss, S.E.; Leenheer, J.A.; McVey, I.F.

1998-01-01

Aqueous attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra of 18 aliphatic di-carboxylic acids are reported as a function of pH. The spectra show isosbestic points and intensity changes which indicate that Beer's law is obeyed, and peak frequencies lie within previously reported ranges for aqueous carboxylates and pure carboxylic acids. Intensity sharing from the symmetric carboxylate stretch is evident in many cases, so that bands which are nominally due to alkyl groups show increased intensity at higher pH. The asymmetric stretch of the HA- species is linearly related to the microscopic acidity constant of the H2A species, with ??pK 2 intervening atoms). The results suggest that aqueous ATR-FTIR may be able to estimate 'intrinsic' pKa values of carboxylic acids, in addition to providing quantitative estimates of ionization. ?? 1998 Elsevier Science B.V. All rights reserved.

Effect of choline carboxylate ionic liquids on biological membranes

PubMed Central

Rengstl, Doris; Kraus, Birgit; Van Vorst, Matthew; Elliott, Gloria D.; Kunz, Werner

2015-01-01

Choline carboxylates, ChCm, with m = 2–10 and choline oleate are known as biocompatible substances, yet their influence on biological membranes is not well-known, and the effect on human skin has not previously been investigated. The short chain choline carboxylates ChCm with m = 2, 4, 6 act as hydrotropes, solubilizing hydrophobic compounds in aqueous solution, while the longer chain choline carboxylates ChCm with m = 8,10 and oleate are able to form micelles. In the present study, the cytotoxicity of choline carboxylates was tested using HeLa and SK-MEL-28 cells. The influence of these substances on liposomes prepared from dipalmitoylphosphatidylcholine (DPPC) was also evaluated to provide insights on membrane interactions. It was observed that the choline carboxylates with a chain length of m > 8 distinctly influence the bilayer, while the shorter ones had minimal interaction with the liposomes. PMID:25444662

Calcium channel blockers inhibit endogenous pyrogen fever in rats and rabbits.

PubMed

Stitt, J T; Shimada, S G

1991-09-01

We have previously shown that febrile responses in both rats and rabbits are elicited by the intravenous injection of a semipurified endogenous pyrogen (EP) prepared from human monocytes. We are now presenting evidence that these febrile responses are mediated via activation of Ca2+ channels by EP. The febrile responses of male New Zealand White rabbits and Sprague-Dawley rats to a standard dose of EP were determined at their respective thermoneutral ambient temperatures. The animals were then treated with Ca2+ channel blocker verapamil (7.5 mg/kg iv) 30-60 min before the EP challenge. In every case the febrile response to EP was markedly attenuated after verapamil pretreatment, while administration of verapamil by itself had no detectable effect on body temperature. Another Ca2+ channel blocker, nifedipine (5 mg/kg iv), was shown to possess antipyretic activity in rats also. To localize where in the fever pathway these Ca2+ channel blockers were acting, we investigated the effect of verapamil at the same dose on fevers that were produced by microinjection of prostaglandin E (PGE) directly into the brain. These PGE fevers were unaffected by verapamil pretreatment, indicating that the antipyretic action of Ca2+ channel blockers occurs before the formation of PGE in response to EP stimulation. The most likely locus of action is the activation of the enzyme phospholipase A2, which regulates the production of arachidonic acid from cellular phospholipids in the prostanoid cascade.

Starch blockers--their effect on calorie absorption from a high-starch meal.

PubMed

Bo-Linn, G W; Santa Ana, C A; Morawski, S G; Fordtran, J S

1982-12-02

It has been known for more than 25 years that certain plant foods, such as kidney beans and wheat, contain a substance that inhibits the activity of salivary and pancreatic amylase. More recently, this antiamylase has been purified and marketed for use in weight control under the generic name "starch blockers." Although this approach to weight control is highly popular, it has never been shown whether starch-blocker tablets actually reduce the absorption of calories from starch. Using a one-day calorie-balance technique and a high-starch (100 g) meal (spaghetti, tomato sauce, and bread), we measured the excretion of fecal calories after normal subjects had taken either placebo or starch-blocker tablets. If the starch-blocker tablets had prevented the digestion of starch, fecal calorie excretion should have increased by 400 kcal. However, fecal calorie excretion was the same on the two test days (mean +/- S.E.M., 80 +/- 4 as compared with 78 +/- 2). We conclude that starch-blocker tablets do not inhibit the digestion and absorption of starch calories in human beings.

Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

PubMed

Iwata, S; Nomoto, M; Fukuda, T

1996-10-01

The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

Distributed Pore Chemistry in Porous Organic Polymers

NASA Technical Reports Server (NTRS)

Koontz, Steven L. (Inventor)

1999-01-01

A method for making a biocompatible polymer article using a uniform atomic oxygen treatment is disclosed. The substrate may be subsequently optionally grated with a compatibilizing compound. Compatibilizing compounds may include proteins, phosphorylcholine groups, platelet adhesion preventing polymers, albumin adhesion promoters, and the like. The compatibilized substrate may also have a living cell layer adhered thereto. The atomic oxygen is preferably produced by a flowing afterglow microwave discharge. wherein the substrate resides in a sidearm out of the plasma. Also, methods for culturing cells for various purposes using the various membranes are disclosed as well. Also disclosed are porous organic polymers having a distributed pore chemistry (DPC) comprising hydrophilic and hydrophobic regions. and a method for making the DPC by exposing the polymer to atomic oxygen wherein the rate of hydrophilization is greater than the rate of mass loss.

Distributed Pore Chemistry in Porous Organic Polymers in Tissue Culture Flasks

NASA Technical Reports Server (NTRS)

Koontz, Steven L. (Inventor)

1999-01-01

A method for making a biocompatible polymer article using a uniform atomic oxygen treatment is disclose. The substrate may be subsequently optionally grated with a compatibilizing compound. Compatibilizing compounds may include proteins, phosphorylcholine groups, platelet adhesion preventing polymers, albumin adhesion promoters, and the like. The compatibilized substrate may also have a living cell layer adhered thereto. The atomic oxygen is preferably produced by a flowing afterglow microwave discharge, wherein the substrate resides in a sidearm out of the plasma. Also, methods for culturing cells for various purposes using the various membranes are disclosed as well. Also disclosed are porous organic polymers having a distributed pore chemistry (DPC) comprising hydrophilic and hydrophobic regions, and a method for making the DPC by exposing the polymer to atomic oxygen wherein the rate of hydrophilization is greater than the rate of mass loss.

Distributed Pore Chemistry in Porous Organic Polymers

NASA Technical Reports Server (NTRS)

Koontz, Steven L. (Inventor)

1998-01-01

A method for making a biocompatible polymer article using a uniform atomic oxygen treatment is disclosed. The sub-strate may be subsequently optionally grated with a compatibilizing compound. Compatibilizing compounds may include proteins, phosphorylcholine groups, platelet adhesion preventing polymers, albumin adhesion promoters, and the like. The compatibilized substrate may also have a living cell layer adhered thereto. The atomic oxygen is preferably produced by a flowing afterglow microwave discharge, wherein the substrate resides in a sidearm out of the plasma. Also, methods for culturing cells for various purposes using the various membranes are disclosed as well. Also disclosed are porous organic polymers having a distributed pore chemistry (DPC) comprising hydrophilic and hydrophobic region, and a method for making the DPC by exposing the polymer to atomic oxygen wherein the rate of hydrophilization is greater than the rate of mass loss.

Cell-Culture Reactor Having a Porous Organic Polymer Membrane

NASA Technical Reports Server (NTRS)

Koontz, Steven L. (Inventor)

2000-01-01

A method for making a biocompatible polymer article using a uniform atomic oxygen treatment is disclosed. The substrate may be subsequently optionally grated with a compatibilizing compound. Compatibilizing compounds may include proteins, phosphory1choline groups, platelet adhesion preventing polymers, albumin adhesion promoters, and the like. The compatibilized substrate may also have a living cell layer adhered thereto. The atomic oxygen is preferably produced by a flowing afterglow microwave discharge, wherein the substrate resides in a sidearm out of the plasma. Also, methods for culturing cells for various purposes using the various membranes are disclosed as well. Also disclosed are porous organic polymers having a distributed pore chemistry (DPC) comprising hydrophilic and hydrophobic regions, and a method for making the DPC by exposing the polymer to atomic oxygen wherein the rate of hydrophilization is greater than the rate of mass loss.

Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries.

PubMed

Harikae, Kyoko; Miura, Kento; Shinomura, Mai; Matoba, Shogo; Hiramatsu, Ryuji; Tsunekawa, Naoki; Kanai-Azuma, Masami; Kurohmaru, Masamichi; Morohashi, Ken-Ichirou; Kanai, Yoshiakira

2013-07-01

In mammalian sex determination, SRY directly upregulates the expression of SOX9, the master regulatory transcription factor in Sertoli cell differentiation, leading to testis formation. Without SRY action, the bipotential gonadal cells become pre-granulosa cells, which results in ovarian follicle development. When, where and how pre-granulosa cells are determined to differentiate into developing ovaries, however, remains unclear. By monitoring SRY-dependent SOX9 inducibility (SDSI) in an Sry-inducible mouse system, we were able to identify spatiotemporal changes in the sexual bipotentiality/plasticity of ovarian somatic cells throughout life. The early pre-granulosa cells maintain the SDSI until 11.5 d.p.c., after which most pre-granulosa cells rapidly lose this ability by 12.0 d.p.c. Unexpectedly, we found a subpopulation of the pre-granulosa cells near the mesonephric tissue that continuously retains SDSI throughout fetal and early postnatal stages. After birth, these SDSI-positive pre-granulosa cells contribute to the initial round of folliculogenesis by the secondary follicle stage. In experimental sex reversal of 13.5-d.p.c. ovaries grafted into adult male nude mice, the differentiated granulosa cells re-acquire the SDSI before other signs of masculinization. Our data provide direct evidence of an unexpectedly high sexual heterogeneity of granulosa cells in developing mouse ovaries in a stage- and region-specific manner. Discovery of such sexually bipotential granulosa cells provides a novel entry point to the understanding of masculinization in various cases of XX disorders of sexual development in mammalian ovaries.

Ca2+ channel blockers interact with alpha 2-adrenergic receptors in rabbit ileum.

PubMed

Homaidan, F R; Donowitz, M; Wicks, J; Cusolito, S; el Sabban, M E; Weiland, G A; Sharp, W G

1988-04-01

An interaction between Ca2+ channel blockers and alpha 2-adrenergic receptors has been demonstrated in rabbit ileum by studying the effect of clonidine on active electrolyte transport, under short-circuited conditions, in the presence and absence of several Ca2+ channel blocking agents. Clonidine, verapamil, diltiazem, cadmium, and nitrendipine all decrease short-circuit current and stimulate NaCl absorption to different extents with clonidine having the largest effect. Exposure to verapamil, diltiazem, and cadmium inhibited the effects of clonidine on transport, whereas nitrendipine had no such effect. Verapamil, diltiazem, and cadmium, but not nitrendipine, also decreased the specific binding of [3H]alpha 2-adrenergic agents to a preparation of ileal basolateral membranes explaining the observed decrease in the transport effects of clonidine. The effective concentrations of the Ca2+ channel blockers that inhibited the effects of clonidine on transport were fairly similar to the concentrations needed to inhibit its specific binding. The displacement of clonidine by calcium channel blockers is ascribed to a nonspecific effect of these agents, although the possibility that their effects are exerted via their binding to the calcium channels is not excluded.

β-Blockers on Discharge From Acute Atrial Fibrillation Are Associated With Decreased Mortality and Lower Cerebrovascular Accidents in Patients With Heart Failure and Reduced Ejection Fraction.

PubMed

Abi Khalil, Charbel; Zubaid, Mohammad; Asaad, Nidal; Rashed, Wafa A; Hamad, Adel Khalifa; Singh, Rajvir; Al Suwaidi, Jassim

2018-04-01

The benefits of β-blockers in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) are controversial. The Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department (ED). We studied the incidence of 6- and 12-month mortality, hospitalization for HF or AF, and stroke/transient ischemic attacks (TIAs) in patients with HFrEF, in relation to β-blockers on discharge from the ED or the subsequent hospital stay. Of the 344 patients with HFrEF and AF in the GULF-SAFE, 177 patients (53%) were discharged on β-blockers. Mortality was lower in those patients compared with the non-β-blockers group at 6 and 12 months (odds ratios [ORs] 0.31, 95% CI [0.16-0.61]; OR 0.30, 95% CI [0.16-0.55]; P = .001 for both, respectively), so was the risk of stroke/TIAs. However, hospitalizations for AF increased in the β-blockers group. Even after adjustment for several risk variables in 2 different models, the beneficial effect of β-blockers on mortality persisted, at the cost of more hospitalization for AF.

Multilayer polymer light-emitting diodes by blade coating method

NASA Astrophysics Data System (ADS)

Tseng, Shin-Rong; Meng, Hsin-Fei; Lee, Kuan-Chen; Horng, Sheng-Fu

2008-10-01

Multilayer polymer light-emitting diodes fabricated by blade coating are presented. Multilayer of polymers can be easily deposited by blade coating on a hot plate. The multilayer structure is confirmed by the total thickness and the cross section view in the scanning electron microscope. The film thickness variation is only 3.3% in 10cm scale and the film roughness is about 0.3nm in the micron scale. The efficiency of single layer poly(para-phenylene vinylene) copolymer Super Yellow and poly(9,9-dioctylfluorene) (PFO, deep blue) devices are 9 and 1.7cd/A, respectively, by blade coating. The efficiency of the PFO device is raised to 2.9cd/A with a 2-(4-tert-butylphenyl)-5-(4-biphenylyl)-1,3,4-oxadiazole (PBD) hole-blocking layer and to 2.3cd/A with a poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(4-sec-butylphenyl))diphenylamine)] elec-tron-blocking layer added by blade coating.

Molecular cloning and functional analysis of ESGP, an embryonic stem cell and germ cell specific protein.

PubMed

Chen, Yan-Mei; Du, Zhong-Wei; Yao, Zhen

2005-12-01

Several putative Oct-4 downstream genes from mouse embryonic stem (ES) cells have been identified using the suppression-subtractive hybridization method. In this study, one of the novel genes encoding an ES cell and germ cell specific protein (ESGP) was cloned by rapid amplification of cDNA ends. ESGP contains 801 bp encoding an 84 amino acid small protein and has no significant homology to any known genes. There is a signal peptide at the N-terminal of ESGP protein as predicted by SeqWeb (GCG) (SeqWeb version 2.0.2, http://gcg.biosino.org:8080/). The result of immunofluorescence assay suggested that ESGP might encode a secretory protein. The expression pattern of ESGP is consistent with the expression of Oct-4 during embryonic development. ESGP protein was detected in fertilized oocyte, from 3.5 day postcoital (dpc) blastocyst to 17.5 dpc embryo, and was only detected in testis and ovary tissues in adult. In vitro, ESGP was only expressed in pluripotent cell lines, such as embryonic stem cells, embryonic caoma cells and embryonic germ cells, but not in their differentiated progenies. Despite its specific expression, forced expression of ESGP is not indispensable for the effect of Oct-4 on ES cell self-renewal, and does not affect the differentiation to three germ layers.

Effects of diltiazem or verapamil on calcium uptake and release from chicken skeletal muscle sarcoplasmic reticulum.

PubMed

Paydar, Mehrak Javadi; Pousti, Abbas; Farsam, Hasan; Amanlou, Massoud; Mehr, Shahram Ejtemaei; Dehpour, Ahmad Reza

2005-11-01

The purpose of this study was to determine the effects of 2 Ca2+ channel blockers, verapamil and diltiazem, on calcium loading (active Ca2+ uptake) and the following Ca2+ release induced by silver ion (Ag+) and Ca2+ from the membrane of heavy sarcoplasmic reticulum (SR) of chicken skeletal muscle. A fluorescent probe technique was employed to determine the calcium movement through the SR. Pretreatment of the medium with diltiazem and verapamil resulted in a significant decrease in the active Ca2+ uptake, with IC50 of about 290 micromol/L for verapamil and 260 micromol/L for diltiazem. Inhibition of Ca2+ uptake was not due to the development of a substantial drug-dependent leak of Ca2+ from the SR. It might, in part, have been mediated by a direct inhibitory effect of these drugs on the Ca2+ ATPase activity of the SR Ca2+ pump. We confirmed that Ca2+ channel blockers, administered after SR Ca2+ loading and before induction of Ca2+ release, caused a dose-dependent inhibition of both Ca2+- and Ag+-induced Ca2+ release rate. Moreover, if Ca2+ channel blockers were administered prior to SR Ca2+ loading, in spite of Ca2+ uptake inhibition the same reduction in Ca2+- and Ag+-induced Ca2+ release rate was seen. We showed that the inhibition of Ag+-induced Ca2+ release by L-channel blockers is more sensitive than Ca2+-induced Ca2+ release inhibition, so the IC50 for Ag+- and Ca2+-induced Ca2+ release was about 100 and 310 micromol/L for verapamil and 79 and 330 micromol/L for diltiazem, respectively. Our results support the evidence that Ca2+ channel blockers affect muscle microsome of chicken skeletal muscle by 2 independent mechanisms: first, reduction of Ca2+ uptake rate and Ca2+-ATPase activity inhibition, and second, inhibition of both Ag+- and Ca2+-induced Ca2+ release by Ca2+ release channels. These findings confirm the direct effect of Ca2+ channel blockers on calcium release channels. Our results suggest that even if the SR is incompletely preloaded with Ca2+ because of inhibition of Ca2+ uptake by verapamil and diltiazem, no impairment in Ca2+ release occurs.

Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Tian, Jinhui; Zhou, Jing; Liu, Yali; Liu, Zhishun

2016-01-01

Alpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96–6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27–7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07–2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57–3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95–4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08–4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07–2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS. PMID:27759111

Histoplasmosis Complicating Tumor Necrosis Factor–α Blocker Therapy: A Retrospective Analysis of 98 Cases

PubMed Central

Vergidis, Paschalis; Avery, Robin K.; Wheat, L. Joseph; Dotson, Jennifer L.; Assi, Maha A.; Antoun, Smyrna A.; Hamoud, Kassem A.; Burdette, Steven D.; Freifeld, Alison G.; McKinsey, David S.; Money, Mary E.; Myint, Thein; Andes, David R.; Hoey, Cynthia A.; Kaul, Daniel A.; Dickter, Jana K.; Liebers, David E.; Miller, Rachel A.; Muth, William E.; Prakash, Vidhya; Steiner, Frederick T.; Walker, Randall C.; Hage, Chadi A.

2015-01-01

Background. Histoplasmosis may complicate tumor necrosis factor (TNF)–α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06–14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03–1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1–69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months. PMID:25870331

Beta-Blockers, Trimethoprim-Sulfamethoxazole, and the Risk of Hyperkalemia Requiring Hospitalization in the Elderly: A Nested Case-Control Study

PubMed Central

Weir, Matthew A.; Juurlink, David N.; Gomes, Tara; Mamdani, Muhammad; Hackam, Daniel G.; Jain, Arsh K.

2010-01-01

Background and objectives: The simultaneous use of beta adrenergic receptor blockers (β-blockers) and trimethoprim-sulfamethoxazole (TMP-SMX) may confer a high risk of hyperkalemia. Design, setting, participants, & measurements: Two nested case-control studies were conducted to examine the association between hospitalization for hyperkalemia and the use of TMP-SMX in older patients receiving β-blockers. Linked health administrative records from Ontario, Canada, were used to assemble a cohort of 299,749 β-blockers users, aged 66 years or older and capture data regarding medication use and hospital admissions for hyperkalemia. Results: Over the study period from 1994 to 2008, 189 patients in this cohort were hospitalized for hyperkalemia within 14 days of receiving a study antibiotic. Compared with amoxicillin, the use of TMP-SMX was associated with a substantially greater risk of hyperkalemia requiring hospital admission (adjusted odds ratio, 5.1; 95% confidence interval [CI], 2.8 to 9.4). No such risk was identified with ciprofloxacin, norfloxacin, or nitrofurantoin. When dosing was considered, the association was greater at higher doses of TMP-SMX. When the primary analysis was repeated in a cohort of non-β-blocker users, the risk of hyperkalemia comparing TMP-SMX to amoxicillin was not significantly different from that found among β-blocker users. Conclusions: Although TMP-SMX is associated with an increased risk of hyperkalemia in older adults, these findings show no added risk when used in combination with β-blockers. PMID:20595693

Prognostic role of prostate-specific antigen and prostate volume for the risk of invasive therapy in patients with benign prostatic hyperplasia initially managed with alpha1-blockers and watchful waiting.

PubMed

Mochtar, C A; Kiemeney, L A L M; Laguna, M P; van Riemsdijk, M M; Barnett, G S; Debruyne, F M J; de la Rosette, J J M C H

2005-02-01

To investigate the prognostic role of prostate-specific antigen (PSA) level and prostate volume (PV) for the need for benign prostatic hyperplasia (BPH)-related invasive therapy among patients initially treated with an alpha1-blocker or watchful waiting (WW) in real-life clinical practice. Data were collected from 2264 consecutive patients with clinical BPH. Patients initially treated with an alpha1-blocker or WW were included in this study. They were stratified by baseline PSA level (less than 1.5, 1.5 to less than 3.0, 3.0 to 10.0 ng/mL) and PV (less than 30 and 30 to 200 cm3), and analyzed for the time to BPH-related invasive therapy. Of the 2264 patients, 389 treated with alpha1-blockers and 553 who chose WW were included. Across the PSA and PV strata, the alpha1-blocker group had worse symptoms, peak flow, postvoid residual urine volumes, and obstruction than did the WW group. Increasing PSA levels produced an increase in the 5-year cumulative risk of invasive treatment: 20%, 34%, and 44% in the alpha1-blocker and 8%, 9%, and 15% in the WW group for a PSA level of less than 1.5, 1.5 to less than 3.0, and 3.0 to 10.0 ng/mL, respectively. The hazard ratio for the highest compared with the lowest PSA strata was 2.8 for alpha1-blocker and 2.7 for WW patients. An increasing PV increased the 5-year cumulative risk from 21% to 35% in the alpha1-blocker group and 8% to 11% in the WW group. The hazard ratio for the large versus small prostates in the alpha1-blocker group was 1.8 and in the WW group was 1.0. A higher PSA level and larger PV resulted in a greater risk of BPH-related invasive therapy that was more pronounced in the alpha1-blocker than in the WW patients. However, symptom severity, flow parameters, and obstruction grade may have contributed to the difference in risk between the two treatment groups.

Quantum chemical investigation of the primary thermal pyrolysis reactions of the sodium carboxylate group in a brown coal model.

PubMed

Li, Jian; Zhang, Baisheng; Zhang, Zhiqiang; Yan, Kefeng; Kang, Lixun

2014-12-01

The primary pyrolysis mechanisms of the sodium carboxylate group in sodium benzoate-used as a model compound of brown coal-were studied by performing quantum chemical computations using B3LYP and the CBS method. Various possible reaction pathways involving reactions such as unimolecular and bimolecular decarboxylation and decarbonylation, crosslinking, and radical attack in the brown coal matrix were explored. Without the participation of reactive radicals, unimolecular decarboxylation to release CO2 was calculated to be the most energetically favorable primary reaction pathway at the B3LYP/6-311+G (d, p) level of theory, and was also found to be more energetically favorable than decarboxylation of an carboxylic acid group. When CBS-QBS results were included, crosslinking between the sodium carboxylate group and the carboxylic acid and the decarboxylation of the sodium carboxylate group (catalyzed by the phenolic hydroxyl group) were found to be possible; this pathway competes with unimolecular decarboxylation of the sodium carboxylate group. Provided that H and CH3 radicals are present in the brown coal matrix and can access the sodium carboxylate group, accelerated pyrolysis of the sodium carboxylate group becomes feasible, leading to the release of an Na atom or an NaCO2 radical at the B3LYP/6-311+G (d, p) or CBS-QB3 level of theory, respectively.

Promotion Effect of Apo-9'-fucoxanthinone from Sargassum muticum on Hair Growth via the Activation of Wnt/β-Catenin and VEGF-R2.

PubMed

Kang, Jung-Il; Yoo, Eun-Sook; Hyun, Jin-Won; Koh, Young-Sang; Lee, Nam Ho; Ko, Mi-Hee; Ko, Chang-Sik; Kang, Hee-Kyoung

2016-01-01

This study was conducted to evaluate the effects of Sargassum muticum extract and apo-9'-fucoxanthinone, a principal component of S. muticum, on hair growth. When rat vibrissa follicles were treated with S. muticum extract for 21 d, the hair-fiber lengths for the vibrissa follicles increased significantly. Treatment with the S. muticum extract and the EtOAc fraction of the S. muticum extract markedly increased the proliferation of dermal papilla cells (DPCs) and decreased the 5α-reductase activity. In addition, the EtOAc fraction of the S. muticum extract significantly promoted anagen initiation in C57BL/6 mice. Especially, apo-9'-fucoxanthinone, an active constituent from the S. muticum extract, caused an increase in DPC proliferation and a decrease in 5α-reductase activity. To elucidate the molecular mechanisms of apo-9'-fucoxanthinone on the proliferation of DPCs, we examined the level of various signaling proteins. Apo-9'-fucoxanthinone increased the level of vascular endothelial growth factor receptor-2 (VEGF-R2), Wnt/β-catenin signaling proteins such as phospho(ser9)-glycogen synthase kinase-3β (GSK-3β) and phospho(ser552)-β-catenin, whereas apo-9'-fucoxanthinone did not affect the transforming growth factor-β (TGF-β) signaling proteins such as Smad2/3. These results suggest that apo-9'-fucoxanthinone from S. muticum could have the potential for hair growth with DPC proliferation via the activation of Wnt/β-catenin signaling and the VEGF-R2 pathway.

New trends and applications in carboxylation for isotope chemistry.

PubMed

Bragg, Ryan A; Sardana, Malvika; Artelsmair, Markus; Elmore, Charles S

2018-05-08

Carboxylations are an important method for the incorporation of isotopically labeled 14 CO 2 into molecules. This manuscript will review labeled carboxylations since 2010 and will present a perspective on the potential of recent unlabeled methodology for labeled carboxylations. The perspective portion of the manuscript is broken into 3 major sections based on product type, arylcarboxylic acids, benzylcarboxylic acids, and alkyl carboxylic acids, and each of those sections is further subdivided by substrate. © 2018 AstraZeneca. Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons, Ltd.

Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis

PubMed Central

Ventre, Sandrine; Petronijevic, Filip R.; MacMillan, David W. C.

2016-01-01

The direct conversion of aliphatic carboxylic acids to the corresponding alkyl fluorides has been achieved via visible light-promoted photoredox catalysis. This operationally simple, redox-neutral fluorination method is amenable to a wide variety of carboxylic acids. Photon-induced oxidation of carboxylates leads to the formation of carboxyl radicals, which upon rapid CO2-extrusion and F• transfer from a fluorinating reagent yield the desired fluoroalkanes with high efficiency. Experimental evidence indicates that an oxidative quenching pathway is operable in this broadly applicable fluorination protocol. PMID:25881929

FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice.

PubMed

Marongiu, Mara; Marcia, Loredana; Pelosi, Emanuele; Lovicu, Mario; Deiana, Manila; Zhang, Yonqing; Puddu, Alessandro; Loi, Angela; Uda, Manuela; Forabosco, Antonino; Schlessinger, David; Crisponi, Laura

2015-07-02

Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation. Foxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR. Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus. Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.

Comparative Effectiveness of Two Oil Adjuvant-Inactivated Avian Influenza H9N2 Vaccines.

PubMed

Kilany, Walid H; Bazid, Abdel-Hamid I; Ali, Ahmed; El-Deeb, Ayman H; El-Abideen, Mohamed A Zain; Sayed, Magdy El; El-Kady, Magdy F

2016-05-01

Low pathogenic avian influenza H9N2 virus infection has been an important risk to the Egyptian poultry industry since 2011. Economic losses have occurred from early infection and co-infection with other pathogens. Therefore, H9N2 vaccination of broiler chicks as young as 7 days old was recommended. The current inactivated H9N2 vaccines (0.5 ml/bird) administered at a reduced dose (0.25 ml/bird) do not guarantee the delivery of an effective dose for broilers. In this study, the efficacy of the reduced-dose volume (0.3 ml/bird), compared with the regular vaccine dose (0.5 ml/bird) of inactivated H9N2 vaccines using two different commercially available adjuvants, was investigated. The vaccines were prepared from the local H9N2 virus (Ck/EG/114940v/NLQP/11) using the same antigen content: 300 hemagglutinating units. Postvaccination (PV) immune response was monitored using the hemagglutination inhibition test. At 4 wk PV, both vaccinated groups were challenged using the homologous H9N2 strain at a 50% egg infective dose (EID50) of 10(6) EID50/bird via the intranasal route. Clinical signs, mortality, and virus shedding in oropharyngeal swabs were monitored at 2, 4, 6, and 10 days postchallenge (DPC). The reduced-dose volume of vaccine induced a significantly faster and higher immune response than the regular volume of vaccine at 2 and 3 wk PV. No significant difference in virus shedding between the two vaccine formulas was found (P ≥ 0.05), and both vaccines were able to stop virus shedding by 6 DPC. The reduced-dose volume of vaccine using a suitable oil adjuvant and proper antigen content can be used effectively for early immunization of broiler chicks.

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

PubMed

Ouwerkerk, W; Voors, A A; Anker, S D; Cleland, J G; Dickstein, K; Filippatos, G; van der Harst, P; Hillege, H L; Lang, C C; Ter Maaten, J M; Ng, L L; Ponikowski, P; Samani, N J; van Veldhuisen, D J; Zannad, F; Metra, M; Zwinderman, A H

2017-06-21

Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial.

PubMed

Contini, Mauro; Apostolo, Anna; Cattadori, Gaia; Paolillo, Stefania; Iorio, Annamaria; Bertella, Erika; Salvioni, Elisabetta; Alimento, Marina; Farina, Stefania; Palermo, Pietro; Loguercio, Monica; Mantegazza, Valentina; Karsten, Marlus; Sciomer, Susanna; Magrì, Damiano; Fiorentini, Cesare; Agostoni, Piergiuseppe

2013-10-03

Several β-blockers, with different pharmacological characteristics, are available for heart failure (HF) treatment. We compared Carvedilol (β1-β2-α-blocker), Bisoprolol (β1-blocker), and Nebivolol (β1-blocker, NO-releasing activity). Sixty-one moderate HF patients completed a cross-over randomized trial, receiving, for 2 months each, Carvedilol, Nebivolol, Bisoprolol (25.6 ± 12.6, 5.0 ± 2.4 and 5.0 ± 2.4 mg daily, respectively). At the end of each period, patients underwent: clinical evaluation, laboratory testing, echocardiography, spirometry (including total DLCO and membrane diffusion), O2/CO2 chemoreceptor sensitivity, constant workload, in normoxia and hypoxia (FiO2=16%), and maximal cardiopulmonary exercise test. No significant differences were observed for clinical evaluation (NYHA classification, Minnesota questionnaire), laboratory findings (including kidney function and BNP), echocardiography, and lung mechanics. DLCO was lower on Carvedilol (18.3 ± 4.8*mL/min/mmHg) compared to Nebivolol (19.9 ± 5.1) and Bisoprolol (20.0 ± 5.0) due to membrane diffusion 20% reduction (*=p<0.0001). Constant workload exercise showed in hypoxia a faster VO2 kinetic and a lower ventilation with Carvedilol. Peripheral and central sensitivity to CO2 was lower in Carvedilol while response to hypoxia was higher in Bisoprolol. Ventilation efficiency (VE/VCO2 slope) was 26.9 ± 4.1* (Carvedilol), 28.8 ± 4.0 (Nebivolol), and 29.0 ± 4.4 (Bisoprolol). Peak VO2 was 15.8 ± 3.6*mL/kg/min (Carvedilol), 16.9 ± 4.1 (Nebivolol), and 16.9 ± 3.6 (Bisoprolol). β-Blockers differently affect several cardiopulmonary functions. Lung diffusion and exercise performance, the former likely due to lower interference with β2-mediated alveolar fluid clearance, were higher in Nebivolol and Bisoprolol. On the other hand, Carvedilol allowed a better ventilation efficiency during exercise, likely via a different chemoreceptor modulation. Results from this study represent the basis for identifying the best match between a specific β-blocker and a specific HF patient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

State-dependent block of CNG channels by dequalinium.

PubMed

Rosenbaum, Tamara; Gordon-Shaag, Ariela; Islas, León D; Cooper, Jeremy; Munari, Mika; Gordon, Sharona E

2004-03-01

Cyclic nucleotide-gated (CNG) ion channels are nonselective cation channels with a high permeability for Ca(2+). Not surprisingly, they are blocked by a number of Ca(2+) channel blockers including tetracaine, pimozide, and diltiazem. We studied the effects of dequalinium, an extracellular blocker of the small conductance Ca(2+)-activated K(+) channel. We previously noted that dequalinium is a high-affinity blocker of CNGA1 channels from the intracellular side, with little or no state dependence at 0 mV. Here we examined block by dequalinium at a broad range of voltages in both CNGA1 and CNGA2 channels. We found that dequalinium block was mildly state dependent for both channels, with the affinity for closed channels 3-5 times higher than that for open channels. Mutations in the S4-S5 linker did not alter the affinity of open channels for dequalinium, but increased the affinity of closed channels by 10-20-fold. The state-specific effect of these mutations raises the question of whether/how the S4-S5 linker alters the binding of a blocker within the ion permeation pathway.

Fabrication of mesoporous metal oxide coated-nanocarbon hybrid materials via a polyol-mediated self-assembly process

NASA Astrophysics Data System (ADS)

Feng, Bingmei; Wang, Huixin; Wang, Dongniu; Yu, Huilong; Chu, Yi; Fang, Hai-Tao

2014-11-01

After clarifying the formation mechanism of a typical metal glycolate precipitate, Ti glycolate, in a polyol-mediated synthesis using acetone as a precipitation medium, we describe a simple template-free approach based on an ethylene glycol-mediated synthesis to fabricate mesoporous metal oxide coated-nanocarbon hybrid materials including TiO2 coated-carbon nanotube (CNT), SnO2 coated-CNT, Cu2O/CuO coated-CNT and TiO2 coated-graphene sheet (GS). In the approach, metal oxide precursors, metal glycolates, were first deposited on CNTs or GSs, and subsequently transformed to the metal oxide coatings by pyrolysis or hydrolysis. By a comparison between the characterization of two TiO2-CNT hybrid materials using carboxylated CNTs and pristine CNTs without carboxyl groups, the driving force for initiating the deposition of metal glycolates on the carboxylated CNTs is confirmed to be the hydrogen bonding between the carboxyl groups and the polymer chains in metal glycolate sols. The electrochemical performances of the mesoporous TiO2 coated-carboxylated CNTs and TiO2-pristine CNT hybrid materials were investigated. The results show that the mesoporous TiO2 coated-carboxylated CNT with a uniform core-shell nanostructure exhibits substantial improvement in the rate performance in comparison with its counterpart from 0.5 C to 100 C because of its higher electronic conductivity and shorter diffusion path for the lithium ion. At the extremely high rate of 100 C, the specific capacity of TiO2 of the former reaches 85 mA h g-1, twice as high as that of the latter.After clarifying the formation mechanism of a typical metal glycolate precipitate, Ti glycolate, in a polyol-mediated synthesis using acetone as a precipitation medium, we describe a simple template-free approach based on an ethylene glycol-mediated synthesis to fabricate mesoporous metal oxide coated-nanocarbon hybrid materials including TiO2 coated-carbon nanotube (CNT), SnO2 coated-CNT, Cu2O/CuO coated-CNT and TiO2 coated-graphene sheet (GS). In the approach, metal oxide precursors, metal glycolates, were first deposited on CNTs or GSs, and subsequently transformed to the metal oxide coatings by pyrolysis or hydrolysis. By a comparison between the characterization of two TiO2-CNT hybrid materials using carboxylated CNTs and pristine CNTs without carboxyl groups, the driving force for initiating the deposition of metal glycolates on the carboxylated CNTs is confirmed to be the hydrogen bonding between the carboxyl groups and the polymer chains in metal glycolate sols. The electrochemical performances of the mesoporous TiO2 coated-carboxylated CNTs and TiO2-pristine CNT hybrid materials were investigated. The results show that the mesoporous TiO2 coated-carboxylated CNT with a uniform core-shell nanostructure exhibits substantial improvement in the rate performance in comparison with its counterpart from 0.5 C to 100 C because of its higher electronic conductivity and shorter diffusion path for the lithium ion. At the extremely high rate of 100 C, the specific capacity of TiO2 of the former reaches 85 mA h g-1, twice as high as that of the latter. Electronic supplementary information (ESI) available. See DOI: 10.1039/C4NR04254A

β-blocker dosage and outcomes after acute coronary syndrome.

PubMed

Allen, Jason E; Knight, Stacey; McCubrey, Raymond O; Bair, Tami; Muhlestein, Joseph Brent; Goldberger, Jeffrey J; Anderson, Jeffrey L

2017-02-01

Although β-blockers increase survival in acute coronary syndrome (ACS) patients, the doses used in trials were higher than doses used in practice, and recent data do not support an advantage of higher doses. We hypothesized that rates of major adverse cardiac events (MACE), all-cause death, myocardial infarction, and stroke are equivalent for patients on low-dose and high-dose β-blocker. Patients admitted to Intermountain Healthcare with ACS and diagnosed with ≥70% coronary stenosis between 1994 and 2013 were studied (N = 7,834). We classified low dose as ≤25% and high dose as ≥50% of an equivalent daily dose of 200 mg of metoprolol. Multivariate analyses were used to test association between low-dose versus high-dose β-blocker dosage and MACE at 0-6 months and 6-24 months. A total of 5,287 ACS subjects were discharged on β-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6-month MACE outcomes rates for the β-blocker dosage (low versus high) were not equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However, subjects on low-dose β-blocker therapy did have a significantly decreased risk of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates of MACE events during the 6-24 months after presentation with ACS were equivalent for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). In ACS patients, rates of MACE for high-dose and low-dose β-blocker doses are similar. These findings question the importance of achieving a high dose of β-blocker in ACS patients and highlight the need for further investigation of this clinical question. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

PubMed

Li, Yanqing; Cheng, Lei; Chen, Xiaoning; Yang, Beibei; Wang, Dehui

2015-01-01

To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p < 0.001). Similarly, the decreases in iNSSs (rhinorrhea, congestion, sneezing, and itching) between the pollen blocker group and the placebo group were also significant (p < 0.05). In addition, in adults, the pollen blocker led to a remarkably significant decrease in TNSS (9.5) compared with placebo (5.4; p < 0.001); in children, the pollen blocker led to a significant decrease in TNSS (8.6) compared with placebo (4.8; p < 0.05). No statistical difference was found in the incidence of adverse events between the two groups (p > 0.05), and no severe systematic reactions were observed. Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study.

PubMed

Morales, Daniel R; Lipworth, Brian J; Donnan, Peter T; Jackson, Cathy; Guthrie, Bruce

2017-01-27

Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD. Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, sex and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression. The cohort consisted of 35,502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers, respectively, during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95% CI 1.83-14.54, P = 0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95% CI 1.08-6.64, P = 0.033 and IRR 12.11, 95% CI 1.02-144.11, P = 0.048, respectively). Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

Effects of β-blocker selectivity on blood pressure variability and stroke: a systematic review.

PubMed

Webb, Alastair John Stewart; Fischer, Urs; Rothwell, Peter Malcolm

2011-08-23

β-Blockers increase variability in systolic blood pressure (SBP), which probably explains their lesser effectiveness in preventing stroke vs myocardial infarction compared with other agents. This increase in variability in blood pressure (BP) may be particularly marked on non-cardioselective agents, potentially calling into question the widespread first-line use of propranolol in migraine with aura, elderly patients with essential tremor or anxiety, and other groups at risk of stroke. We determined β-blocker subclass effects on variability in BP and stroke risk in a systematic review of randomized controlled trials (RCTs) comparing different types of β-blocker with placebo or other agents. We determined pooled estimates of the effect of treatment on group variability in BP (ratio of the variances [VR]) and on the risk of stroke vs myocardial infarction during follow-up. Compared with other antihypertensives, variability in SBP was increased more by nonselective β-blockers (VR=1.34, 1.13-1.59, p =0.002, 25 comparisons, 9,992 patients) than by β1-selective agents (VR=1.09, 95% confidence interval 1.00-1.19, p =0.053, 68 comparisons, 40,746 patients; difference-p =0.038). In direct comparisons, variability in SBP was also significantly lower with β1-selective vs nonselective β-blockers (VR=0.81, 0.68-0.97, p =0.03, 18 comparisons, 954 patients). In comparisons with other antihypertensives, the increase in stroke risk with nonselective β-blockers ([OR]=2.29, 1.32-3.96, p =0.002) was more marked than with β1-selective agents (OR=1.24, 1.08-1.42, p =0.003, difference-p =0.03), as was the risk of stroke relative to the risk of myocardial infarction: OR=1.50 (0.93-2.42) vs 0.99 (0.82-1.19). Use of β1-selective rather than nonselective agents may be advisable when β-blockers are indicated for patients at risk of stroke.

Optimizing catecholaminergic polymorphic ventricular tachycardia therapy in calsequestrin-mutant mice

PubMed Central

Katz, Guy; Khoury, Assad; Kurtzwald, Efrat; Hochhauser, Edith; Porat, Eyal; Shainberg, Asher; Seidman, Jonathan G.; Seidman, Christine E.; Lorber, Abraham; Eldar, Michael; Arad, Michael

2014-01-01

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal arrhythmia provoked by physical or emotional stress and mediated by spontaneous Ca2+ release and delayed after-depolarizations. Beta-adrenergic blockers are the therapy of choice but fail to control arrhythmia in up to 50% of patients. OBJECTIVE To optimize antiarrhythmic therapy in recessively inherited CPVT caused by calsequestrin (CASQ2) mutations. METHODS Murine heart rhythm telemetry was obtained at rest, during treadmill exercise, and after injection of epinephrine. The protocol was repeated after injection of different antiarrhythmic drugs. Results were then validated in human patients. RESULTS Adult CASQ2 mutant mice had complex ventricular arrhythmia at rest and developed bidirectional and polymorphic ventricular tachycardia on exertion. Class I antiarrhythmic agents (procainamide, lidocaine, flecainide) were ineffective in controlling arrhythmia. Propranolol and sotalol attenuated arrhythmia at rest but failed to prevent VT during sympathetic stimulation. The calcium channel blocker verapamil showed a dose-dependent protection against CPVT. Verapamil was more effective than the dihydropyridine L-type Ca2+ channel blocker nifedipine, and its activity was markedly enhanced when combined with propranolol. Human patients homozygous for CASQ2D307H mutation, remaining symptomatic despite chronic β-blocker therapy, underwent exercise testing according to the Bruce protocol with continuous electrocardiogram recording. Verapamil was combined with propranolol at maximum tolerated doses. Adding verapamil attenuated ventricular arrhythmia and prolonged exercise duration in five of 11 patients. CONCLUSION Verapamil is highly effective against catecholamine-induced arrhythmia in mice with CASQ2 mutations and may potentiate the antiarrhythmic activity of β-blockers in humans with CPVT2. PMID:20620233

Survival of Swiss-Webster mouse cerebellar granule neurons is promoted by a combination of potassium channel blockers.

PubMed

Collins, Anthony; Larson, Maureen K; Pfaff, Jilleen E; Ishmael, Jane E

2007-06-15

Cultured cerebellar granule neurons (CGN) are commonly used to assess neurotoxicity, but are routinely maintained in supraphysiological (25 mM) extracellular K(+) concentrations [K(+)](o). We investigated the effect of potassium channel blockade on survival of CGN derived from Swiss-Webster mice in supraphysiological (25 mM) and physiological (5.6 mM) [K(+)](o). CGN were cultured for 5 days in 25 mM K(+), then in 5.6 mM K(+) or 25 mM K(+) (control). Viability, assayed 24 h later by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) reduction and by lactate dehydrogenase (LDH) release, was approximately 50% in 5.6 mM K(+) versus 25 mM K(+) (p<.001). Potassium channel blockers, 2 mM 4-aminopyridine (4-AP), 2 mM tetraethylammonium (TEA) or 1 mM Ba(2+), individually afforded limited protection in 5.6 mM K(+). However, survival in 5.6 mM K(+) with a combination of 4-AP, TEA and Ba(2+) was similar to survival in 25 mM K(+) without blockers (p<.001 versus 5.6 mM K(+) alone). CGN survival in 25 mM K(+) was attenuated 25% by 2 microM nifedipine (p>.001), but nifedipine did not attenuate neuroprotection by K(+) channel blockers. Together, these results suggest that the survival of CGN depends on the K(+) permeability of the membrane rather than the activity of a particular type of K(+) channel, and that the mechanism of neuroprotection by K(+) channel blockers is different from that of elevated [K(+)](o).

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

PubMed

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-05-01

Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. © 2014 The British Pharmacological Society.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

PubMed

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

2013-12-09

To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis

PubMed Central

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-01-01

Aims Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. Methods We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. Results From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l−1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l−1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Conclusions Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. PMID:25377481

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

PubMed

McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

2014-04-01

Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

PubMed Central

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John JV; Califf, Robert M

2013-01-01

Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Setting NAVIGATOR trial. Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. Trial registration ClinicalTrials.gov NCT00097786. PMID:24322398

In silico analysis of the anti-hypertensive drugs impact on myocardial oxygen balance.

PubMed

Guala, A; Leone, D; Milan, A; Ridolfi, L

2017-06-01

Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.

Antihyperalgesic effects of ProTx-II, a Nav1.7 antagonist, and A803467, a Nav1.8 antagonist, in diabetic mice.

PubMed

Tanaka, Ken-Ichiro; Sekino, Shota; Ikegami, Megumi; Ikeda, Hiroko; Kamei, Junzo

2015-01-01

The present study investigated the effects of intrathecal administration of ProTx-II (tarantula venom peptide) and A803467 (5-[4-chloro-phenyl]-furan-2-carboxylic acid [3,5-dimethoxy-phenyl]-amide), selective Nav1.7 and Nav1.8 antagonists, respectively, on thermal hyperalgesia in a painful diabetic neuropathy model of mice. Intrathecal administration of ProTx-II at doses from 0.04 to 4 ng to diabetic mice dose-dependently and significantly increased the tail-flick latency. Intrathecal administration of A803467 at doses from 10 to 100 ng to diabetic mice also dose-dependently and significantly increased the tail-flick latency. However, intrathecal administration of either ProTx-II (4 ng) or A803467 (100 ng) had no effect on the tail-flick latency in nondiabetic mice. The expression of either the Nav1.7 or Nav1.8 sodium channel protein in the dorsal root ganglion in diabetic mice was not different from that in nondiabetic mice. The present results suggest that ProTx-II and A803467, highly selective blockers of Nav1.7 and Nav1.8 sodium channels, respectively, in the spinal cord, can have antihyperalgesic effects in diabetic mice.

Heart rate and use of beta-blockers in stable outpatients with coronary artery disease.

PubMed

Steg, Ph Gabriel; Ferrari, Roberto; Ford, Ian; Greenlaw, Nicola; Tardif, Jean-Claude; Tendera, Michal; Abergel, Hélène; Fox, Kim M

2012-01-01

Heart rate (HR) is an emerging risk factor in coronary artery disease (CAD). However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR. CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%). Mean (SD) age was 64.2 (10.5) years, HR by pulse was 68.3 (10.6) bpm, and by electrocardiogram was 67.2 (11.4) bpm. Overall, 44.0% had HR ≥ 70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR ≥ 70 bpm. HR ≥ 70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents. Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR ≥ 70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

PubMed

Doughty, R N; Rodgers, A; Sharpe, N; MacMahon, S

1997-04-01

Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Impact of organizational infrastructure on beta-blocker and aspirin therapy for acute myocardial infarction.

PubMed

Ellerbeck, Edward F; Bhimaraj, Arvind; Hall, Sandra

2006-09-01

Although organizational change has been advocated as a critical component of quality improvement, there is little data available on the variation and effectiveness of organizational elements in the care of acute myocardial infarction (AMI). This study was designed to examine the impact of organizational infrastructure on the use of aspirin and beta-blockers during and after AMI. We assessed organizational infrastructure for AMI care in 44 hospitals in Kansas and linked these data to patient-specific process of care data collected in Kansas as part of the Cooperative Cardiovascular Project. While controlling for clustering within hospitals, we examined the relationships between hospital infrastructure and use of aspirin and beta-blocker both at admission and discharge. Hospitals varied widely in their inclusion of aspirin and beta-blockers in AMI pathways, protocols, and standardized order sets. Hospitals also varied in the involvement of their physicians in AMI quality improvement and in their ability to identify a physician champion for AMI care. Patients were more likely to receive aspirin on admission in hospitals that included aspirin in their emergency department order sets (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.01-2.48) and were more likely to receive beta-blockers on admission and at discharge if beta-blockers were included in an emergency department protocol or pathway (OR 2.14, 95% CI 1.25-3.77 and OR 3.5, 95% CI 1.14-14.38, respectively). Use of beta-blockers at discharge was also associated with commitment of administration to AMI care and the presence of a physician champion. Quality improvement efforts should include a close examination of the organization of AMI care to assure that critical elements in the care of AMI patients are not inadvertently omitted.

Formation and High-order Carboxylic Acids (RCOOH) in Interstellar Analogous Ices of Carbon Dioxide (CO2) and Methane(CH4)

NASA Astrophysics Data System (ADS)

Zhu, Cheng; Turner, Andrew M.; Abplanalp, Matthew J.; Kaiser, Ralf I.

2018-01-01

This laboratory study simulated the abiotic formation of carboxylic acids (RCOOH) in interstellar analogous ices of carbon dioxide (CO2) and methane (CH4) at 10 K upon exposure to energetic electrons. The chemical processing of the ices and the subsequent warm-up phase were monitored online and in situ, exploiting Fourier Transform Infrared Spectrometry and quadrupole mass spectrometry. Characteristic absorptions of functional groups of carboxylic acids (RCOOH) were observed in the infrared spectra of the irradiated ice. Two proposed reaction mechanisms replicated the kinetic profiles of the carboxylic acids along with the decay profile of the precursors during the irradiation via hydrocarbon formation, followed by carboxylation and/or through acetic acid along with mass growth processes of the alkyl chain. Mass spectra recorded during the warm-up phase demonstrated that these acids are distributed from acetic acid (CH3COOH) up to decanoic acid (C9H19COOH). High-dose irradiation studies (91 ± 14 eV) converted low-molecular-weight acids such as acetic acid (CH3COOH) and propionic acid (C2H5COOH) to higher-molecular-weight carboxylic acids, compared to low-dose irradiation studies (18 ± 3 eV). The traces of the {{{H}}}2{{C}}= {{C}}({OH}{)}2+ (m/z = 60) fragment—a link to linear carboxylic acids—implied that higher-order acids (C n H2n+1COOH, n ≥ 5) are likely branched, which correlates with the recent analysis of the structures of the monocarboxylic acids in the Murchison meteorite.

Does tight heart rate control improve beta-blocker efficacy? An updated analysis of the noncardiac surgical randomized trials.

PubMed

Beattie, W Scott; Wijeysundera, Duminda N; Karkouti, Keyvan; McCluskey, Stuart; Tait, Gordon

2008-04-01

Recent meta-analyses assessing the efficacy of perioperative beta-blockade trials have failed to show a reduction in postoperative morbidity and mortality. Tight control of heart rate (HR) has been suggested to improve these outcomes. Meta-analyses have not considered the influence of tight HR control on the efficacy of perioperative beta-blockade. Using previously published search strategies, we identified all randomized trials evaluating perioperative beta-blockers after noncardiac surgery. This search yielded 10 trials with 2176 patients. We used the data from these studies to correlate measures of HR control with major postoperative outcomes, primarily in-hospital myocardial infarction (MI). Odds ratio (OR) and 95% confidence intervals (CI) were calculated, and metaregression was performed correlating measures of HR control with MI. The combined results of all studies did not show a significant cardioprotective effect of beta-blockers, with considerable heterogeneity among the studies (OR = 0.76; 95% CI = 0.4-1.4; P = 0.38 heterogeneity: I(2) = 34%). However, grouping the trials on the basis of maximal HR showed that trials where the estimated maximal HR was <100 bpm were associated with cardioprotection (OR = 0.23; 95% CI = 0.08-0.65; P = 0.005) whereas trials where the estimated maximal HR was >100 bpm did not demonstrate cardioprotection (OR = 1.17; 95% CI = 0.79-1.80; P = 0.43) with no heterogeneity. Moreover, metaregression of the HR response to beta-blockade against the log OR of postoperative MI demonstrated a linear association between the effect of beta-blockade on the mean, maximal, and variation in HR and the OR of an MI (r(2) = 0.63; P < 0.001) where a larger effect of beta-blockers on HR was associated with a decreased incidence of postoperative MI. Across all studies, beta-blockade resulted in a reduction in postoperative HR (weighted mean difference: 8.6 bpm; 95% CI = -9.6 to -7.6; I(2) = 85.3%) with considerable heterogeneity. This large heterogeneity in HR response to beta-blockade was found to be related, in part, to the type of beta-blocker, specifically, metoprolol, and the concomitant use of calcium channel blockers. Calcium channel blocker use and beta-blockers other than metoprolol resulted in more effective control of HR. There was wide variability in the HR response to beta-blockade. Twenty-five percent of patients receiving beta-blockers had episodes when the HRs were more than 100 bpm, although 15% of placebo patients also had bradycardia, which would have required a dose reduction had they been administered beta-blockers. Finally, this analysis found that perioperative beta-blockade was associated with an increased incidence of bradycardia (OR = 3.49; 95% CI = 2.4-5.9) and congestive heart failure (OR = 1.68; 95% CI = 1.00-2.8). The trials that achieve the most effective control of HR are associated with a reduced incidence of postoperative MI, suggesting that effective control of HR is important for achieving cardioprotection. Second, this analysis demonstrates that administration of beta-blockers does not reliably decrease HRs in all patients, and may be associated with increased side effects. Judicious use of combination therapy with other drugs may be necessary to achieve effective postoperative control of HR.

Carboxylated SiO2-coated α-Fe nanoparticles: towards a versatile platform for biomedical applications.

PubMed

Kohara, Kaori; Yamamoto, Shinpei; Seinberg, Liis; Murakami, Tatsuya; Tsujimoto, Masahiko; Ogawa, Tetsuya; Kurata, Hiroki; Kageyama, Hiroshi; Takano, Mikio

2013-03-28

Carboxylated SiO2-coated α-Fe nanoparticles have been successfully prepared via CaH2-mediated reduction of SiO2-coated Fe3O4 nanoparticles followed by surface carboxylation. These α-Fe-based nanoparticles, which are characterized by ease of coating with additional functional groups, a large magnetization of 154 emu per g-Fe, enhanced corrosion resistivity, excellent aqueous dispersibility, and low cytotoxicity, have potential to be a versatile platform in biomedical applications.

Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.

PubMed

Krogsgaard-Larsen, Niels; Storgaard, Morten; Møller, Charlotte; Demmer, Charles S; Hansen, Jeanette; Han, Liwei; Monrad, Rune N; Nielsen, Birgitte; Tapken, Daniel; Pickering, Darryl S; Kastrup, Jette S; Frydenvang, Karla; Bunch, Lennart

2015-08-13

Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.

Hydrogenation of carboxylic acids with a homogeneous cobalt catalyst.

PubMed

Korstanje, Ties J; van der Vlugt, Jarl Ivar; Elsevier, Cornelis J; de Bruin, Bas

2015-10-16

The reduction of esters and carboxylic acids to alcohols is a highly relevant conversion for the pharmaceutical and fine-chemical industries and for biomass conversion. It is commonly performed using stoichiometric reagents, and the catalytic hydrogenation of the acids previously required precious metals. Here we report the homogeneously catalyzed hydrogenation of carboxylic acids to alcohols using earth-abundant cobalt. This system, which pairs Co(BF4)2·6H2O with a tridentate phosphine ligand, can reduce a wide range of esters and carboxylic acids under relatively mild conditions (100°C, 80 bar H2) and reaches turnover numbers of up to 8000. Copyright © 2015, American Association for the Advancement of Science.

Virtually pure near-infrared electroluminescence from exciplexes at polyfluorene/hexaazatrinaphthylene interfaces

NASA Astrophysics Data System (ADS)

Tregnago, G.; Fléchon, C.; Choudhary, S.; Gozalvez, C.; Mateo-Alonso, A.; Cacialli, F.

2014-10-01

Electronic processes at the heterojunction between chemically different organic semiconductors are of special significance for devices such as light-emitting diodes (LEDs) and photovoltaic diodes. Here, we report the formation of an exciplex state at the heterojunction of an electron-transporting material, a functionalized hexaazatrinaphthylene, and a hole-transporting material, poly(9,9-dioctylfluorene-alt-N-(4-butylphenyl)diphenylamine) (TFB). The energetics of the exciplex state leads to a spectral shift of ˜1 eV between the exciton and the exciplex peak energies (at 2.58 eV and 1.58 eV, respectively). LEDs incorporating such bulk heterojunctions display complete quenching of the exciton luminescence, and a nearly pure near-infrared electroluminescence arising from the exciplex (at ˜1.52 eV) with >98% of the emission at wavelengths above 700 nm at any operational voltage.

Antioxidant activity of beta-blockers: an effect mediated by scavenging reactive oxygen and nitrogen species?

PubMed

Gomes, Ana; Costa, David; Lima, José L F C; Fernandes, Eduarda

2006-07-01

The therapeutic effects of beta-blockers are normally explained by their capacity to block the beta-adrenoceptors, however, some of the beneficial cardiovascular effects shown by this group of compounds have already been associated with the antioxidant properties that some of them seem to possess. The beta-blockers atenolol, labetalol, metoprolol, pindolol, propranolol, sotalol, timolol, and carvedilol were tested for their putative scavenging activity for ROS (O(2)(-), H(2)O(2), HO(.), HOCl, and ROO(.)) and RNS ((.)NO and ONOO(-)). Some of the studied compounds are effective ROS and/or RNS scavengers, these effects being possibly useful in preventing oxidative damage verified in hypertension as well as in other cardiovascular diseases that frequently emerge in association with oxidative stress.

First-principles characterization of formate and carboxyl adsorption on the stoichiometric CeO2(111) and CeO2(110) surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mei, Donghai

2013-05-20

Molecular adsorption of formate and carboxyl on the stoichiometric CeO2(111) and CeO2(110) surfaces was studied using periodic density functional theory (DFT+U) calculations. Two distinguishable adsorption modes (strong and weak) of formate are identified. The bidentate configuration is more stable than the monodentate adsorption configuration. Both formate and carboxyl bind at the more open CeO2(110) surface are stronger. The calculated vibrational frequencies of two adsorbed species are consistent with experimental measurements. Finally, the effects of U parameters on the adsorption of formate and carboxyl over both CeO2 surfaces were investigated. We found that the geometrical configurations of two adsorbed species aremore » not affected by using different U parameters (U=0, 5, and 7). However, the calculated adsorption energy of carboxyl pronouncedly increases with the U value while the adsorption energy of formate only slightly changes (<0.2 eV). The Bader charge analysis shows the opposite charge transfer occurs for formate and carboxyl adsorption where the adsorbed formate is negatively charge whiled the adsorbed carboxyl is positively charged. Interestingly, with the increasing U parameter, the amount of charge is also increased. This work was supported by the Laboratory Directed Research and Development (LDRD) project of the Pacific Northwest National Laboratory (PNNL) and by a Cooperative Research and Development Agreement (CRADA) with General Motors. The computations were performed using the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), which is a U.S. Department of Energy national scientific user facility located at PNNL in Richland, Washington. Part of the computing time was also granted by the National Energy Research Scientific Computing Center (NERSC)« less

Model predictive direct power control for active power decoupled single-phase quasi- Z -source inverter

DOE PAGES

Liu, Yushan; Ge, Baoming; Abu-Rub, Haitham; ...

2016-06-14

In this study, the active power filter (APF) that consists of a half-bridge leg and an ac capacitor is integrated in the single-phase quasi-Z-source inverter (qZSI) in this paper to avoid the second harmonic power flowing into the dc side. The capacitor of APF buffers the second harmonic power of the load, and the ac capacitor allows highly pulsating ac voltage, so that the capacitances of both dc and ac sides can be small. A model predictive direct power control (DPC) is further proposed to achieve the purpose of this newtopology through predicting the capacitor voltage of APF at eachmore » sampling period and ensuring the APF power to track the second harmonic power of single-phase qZSI. Simulation and experimental results verify the model predictive DPC for the APF-integrated single-phase qZSI.« less

Role of parietal regions in episodic memory retrieval: the dual attentional processes hypothesis.

PubMed

Cabeza, Roberto

2008-01-01

Although parietal cortex is frequently activated during episodic memory retrieval, damage to this region does not markedly impair episodic memory. To account for these and other findings, a new dual attentional processes (DAP) hypothesis is proposed. According to this hypothesis, dorsal parietal cortex (DPC) contributes top-down attentional processes guided by retrieval goals, whereas ventral parietal cortex (VPC) contributes bottom-up attentional processes captured by the retrieval output. Consistent with this hypothesis, DPC activity increases with retrieval effort whereas VPC activity increases with confidence in old and new responses. The DAP hypothesis can also account for the overlap of parietal activations across different cognitive domains and for opposing effects of parietal activity on encoding vs. retrieval. Finally, the DAP hypothesis explains why VPC lesions yield a memory neglect syndrome: a deficit in spontaneously reporting relevant memory details but not in accessing the same details when guided by specific questions.

Primary cell culture and morphological characterization of canine dermal papilla cells and dermal fibroblasts.

PubMed

Bratka-Robia, Christine B; Mitteregger, Gerda; Aichinger, Amanda; Egerbacher, Monika; Helmreich, Magdalena; Bamberg, Elmar

2002-02-01

Skin biopsies were taken from female dogs, the primary hair follicles isolated and the dermal papilla dissected. After incubation in supplemented Amniomax complete C100 medium in 24-well culture plates, the dermal papilla cells (DPC) grew to confluence within 3 weeks. Thereafter, they were subcultivated every 7 days. Dermal fibroblast (DFB) cultures were established by explant culture of interfollicular dermis in serum-free medium, where they reached confluence in 10 days. They were subcultivated every 5 days. For immunohistochemistry, cells were grown on cover slips for 24 h, fixed and stained with antibodies against collagen IV and laminin. DPC showed an aggregative growth pattern and formation of pseudopapillae. Intensive staining for collagen IV and laminin could be observed until the sixth passage. DFB grew as branching, parallel lines and showed only weak staining for collagen IV and laminin.

Model predictive direct power control for active power decoupled single-phase quasi- Z -source inverter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yushan; Ge, Baoming; Abu-Rub, Haitham

In this study, the active power filter (APF) that consists of a half-bridge leg and an ac capacitor is integrated in the single-phase quasi-Z-source inverter (qZSI) in this paper to avoid the second harmonic power flowing into the dc side. The capacitor of APF buffers the second harmonic power of the load, and the ac capacitor allows highly pulsating ac voltage, so that the capacitances of both dc and ac sides can be small. A model predictive direct power control (DPC) is further proposed to achieve the purpose of this newtopology through predicting the capacitor voltage of APF at eachmore » sampling period and ensuring the APF power to track the second harmonic power of single-phase qZSI. Simulation and experimental results verify the model predictive DPC for the APF-integrated single-phase qZSI.« less

Observations of cavity polaritons in one-dimensional photonic crystals containing a liquid-crystalline semiconductor based on perylene bisimide units

NASA Astrophysics Data System (ADS)

Sakata, T.; Suzuki, M.; Yamamoto, T.; Nakanishi, S.; Funahashi, M.; Tsurumachi, N.

2017-10-01

We investigated the optical transmission properties of one-dimensional photonic crystal (1D-PC) microcavity structures containing the liquid-crystalline (LC) perylene tetracarboxylic bisimide (PTCBI) derivative. We fabricated the microcavity structures for this study by two different methods and observed the cavity polaritons successfully in both samples. For one sample, since the PTCBI molecules were aligned in the cavity layer of the 1D-PC by utilizing a friction transfer method, vacuum Rabi splitting energy was strongly dependent on the polarization of the incident light produced by the peculiar optical features of the LC organic semiconductor. For the other sample, we did not utilize the friction transfer method and did not observe such polarization dependence. However, we did observe a relatively large Rabi splitting energy of 187 meV, probably due to the improvement of optical confinement effect.

A new accounting system for financial balance based on personnel cost after the introduction of a DPC/DRG system.

PubMed

Nakagawa, Yoshiaki; Takemura, Tadamasa; Yoshihara, Hiroyuki; Nakagawa, Yoshinobu

2011-04-01

A hospital director must estimate the revenues and expenses not only in a hospital but also in each clinical division to determine the proper management strategy. A new prospective payment system based on the Diagnosis Procedure Combination (DPC/PPS) introduced in 2003 has made the attribution of revenues and expenses for each clinical department very complicated because of the intricate involvement between the overall or blanket component and a fee-for service (FFS). Few reports have so far presented a programmatic method for the calculation of medical costs and financial balance. A simple method has been devised, based on personnel cost, for calculating medical costs and financial balance. Using this method, one individual was able to complete the calculations for a hospital which contains 535 beds and 16 clinics, without using the central hospital computer system.

Crystal structure and magnetic properties of two isomeric three-dimensional pyromellitate-containing cobalt(II) complexes.

PubMed

Fabelo, Oscar; Pasán, Jorge; Cañadillas-Delgado, Laura; Delgado, Fernando S; Lloret, Francesc; Julve, Miguel; Ruiz-Pérez, Catalina

2008-09-15

The hydrothermal preparation, crystal structure determination, and magnetic study of two isomers made up of 1,2,4,5-benzenetetracarboxylate and high-spin Co(II) ions of formula [Co2(bta)(H2O)4]n x 2n H2O (1 and 2; H4bta = 1,2,4,5-benzenetetracarboxylic acid) are reported. 1 and 2 are three-dimensional compounds whose structures can be described as (4,4) rectangular layers of trans-diaquacobalt(II) units with the bta(4-) anion acting as tetrakis-monodentate ligand through the four carboxylate groups, which are further connected through other trans-[Co(H2O)2](2+) (1) and planar [Co(H2O)4](2+) (2) entities, with the bridging units being a carboxylate group in either the anti-syn (1) or syn-syn (2) conformations and a water molecule (2). The study of the magnetic properties of 1 and 2 in the temperature range 1.9-300 K shows the occurrence of weak antiferromagnetic interactions between the high-spin Co(II) ions, with the strong decrease of chi(M)T upon cooling being mainly due to the depopulation of the higher energy Kramers doublets of the six-coordinated Co(II) ions. The computed values of the exchange coupling between the Co(II) ions across anti-syn carboxylate (1) and syn-syn carboxylate/water (2) bridges are J = -0.060 (1) and -1.90 (2) cm(-1) (with the Hamiltonian being defined as H = -Jsigma(i,j)S(i) x S(j)). These values follow the different conformations of the carboxylate bridge in 1 (anti-syn) and 2 (syn-syn) with the occurrence of a double bridge in 2 (water/carboxylate).

Stimulation of hepatic glutathione formation by administration of L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-prolinase substrate.

PubMed Central

Williamson, J M; Meister, A

1981-01-01

5-Oxo-L-prolinase, the enzyme that catalyzes the conversion of 5-oxo-L-proline to L-glutamate coupled to the cleavage of ATP to ADP and Pi, also acts on L-2-oxothiazolidine-4-carboxylate (an analog of 5-oxoproline in which the 4-methylene moiety is replaced by sulfur) and ATP to yield cysteine and ADP. The enzyme, which exhibits an affinity for the analog similar to that for the natural substrate, is inhibited by the analog in vitro and in vivo. L-2-oxothiazolidine-4-carboxylate thus serves as a potent inhibitor of the gamma-glutamyl cycle at the step of 5-oxoprolinase. Administration of L-2-oxothiazolidine-4-carboxylate to mice that had been depleted of hepatic glutathione led to restoration of normal hepatic glutathione levels. Since L-2-oxothiazolidine-4-carboxylate is an excellent substrate of the enzyme, it may serve as an intracellular delivery system for cysteine and thus has potential as a therapeutic agent for conditions in which there is depletion of hepatic glutathione. PMID:6940159

β-Adrenergic modulation of cancer cell proliferation: available evidence and clinical perspectives.

PubMed

Coelho, Marisa; Soares-Silva, Cátia; Brandão, Daniela; Marino, Franca; Cosentino, Marco; Ribeiro, Laura

2017-02-01

In this review, we aimed to present and discuss the available preclinical and epidemiological evidences regarding the modulation of cancer cell proliferation by β-adrenoceptors (β-AR), with a specific focus on the putative effects of β-blockers according to their pharmacological properties. A comprehensive review of the published literature was conducted, and the evidences concerning the involvement of β-AR in cancer as well as the possible role of β-blockers were selected and discussed. The majority of reviewed studies show that: (1) All the cancer types express both β1- and β2-AR, with the exception of neuroblastoma only seeming to express β2-AR; (2) adrenergic agonists are able to increase proliferation of several types of cancers; (3) the proliferative effect seems to be mediated by both β1- and β2-AR; (4) binding to β-AR results in a cAMP transient flux which activates two major downstream effector systems: protein kinase A and EPAC and (5) β-blockers might be putative adjuvants for cancer treatment. Overall, the reviewed studies show strong evidences that β-AR activation, through several intracellular mechanisms, modulate tumor cell proliferation suggesting β-blockers can be a feasible therapeutic approach to antagonize β-adrenergic response or have a protective effect per se. This review highlight the need for intensifying the research not only on the molecular mechanisms underlying the β-adrenergic influence in cancer, but also on the implications of biased agonism of β-blockers as potential antitumor agents.

Effects of cilnidipine on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: association with BNP and aldosterone levels.

PubMed

Tanaka, Masami; Sekioka, Risa; Nishimura, Takeshi; Ichihara, Atsuhiro; Itoh, Hiroshi

2014-12-01

Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Protective effects of efonidipine, a T- and L-type calcium channel blocker, on renal function and arterial stiffness in type 2 diabetic patients with hypertension and nephropathy.

PubMed

Sasaki, Hidehisa; Saiki, Atsuhito; Endo, Kei; Ban, Noriko; Yamaguchi, Takashi; Kawana, Hidetoshi; Nagayama, Daizi; Ohhira, Masahiro; Oyama, Tomokazu; Miyashita, Yoh; Shirai, Kohji

2009-10-01

The three types of calcium channel blocker (CCB), L-, T- and N-type, possess heterogeneous actions on endothelial function and renal microvascular function. In the present study, we evaluated the effects of two CCBs, efonidipine and amlodipine, on renal function and arterial stiffness. Forty type 2 diabetic patients with hypertension and nephropathy receiving angiotensin receptor II blockers were enrolled and randomly divided into two groups: the efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day and the amlodipine group was admin-istered amlodipine besilate 5 mg/day for 12 months. Arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Changes in blood pressure during the study were almost the same in the two groups. Sig-nificant increases in serum creatinine and urinary albumin and a significant decrease in the esti-mated glomerular filtration rate were observed in the amlodipine group, but not in the efonidipine group. On the other hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxy-guanosine and CAVI were observed after 12 months in the efonidipine group, but not in the amlo-dipine group. These results suggest that efonidipine, which is both a T-type and L-type calcium chan-nel blocker, has more favorable effects on renal function, oxidative stress and arterial stiffness than amlodipine, an L-type calcium channel blocker.

ATM and KAT5 safeguard replicating chromatin against formaldehyde damage

PubMed Central

Ortega-Atienza, Sara; Wong, Victor C.; DeLoughery, Zachary; Luczak, Michal W.; Zhitkovich, Anatoly

2016-01-01

Many carcinogens damage both DNA and protein constituents of chromatin, and it is unclear how cells respond to this compound injury. We examined activation of the main DNA damage-responsive kinase ATM and formation of DNA double-strand breaks (DSB) by formaldehyde (FA) that forms histone adducts and replication-blocking DNA-protein crosslinks (DPC). We found that low FA doses caused a strong and rapid activation of ATM signaling in human cells, which was ATR-independent and restricted to S-phase. High FA doses inactivated ATM via its covalent dimerization and formation of larger crosslinks. FA-induced ATM signaling showed higher CHK2 phosphorylation but much lower phospho-KAP1 relative to DSB inducers. Replication blockage by DPC did not produce damaged forks or detectable amounts of DSB during the main wave of ATM activation, which did not require MRE11. Chromatin-monitoring KAT5 (Tip60) acetyltransferase was responsible for acetylation and activation of ATM by FA. KAT5 and ATM were equally important for triggering of intra-S-phase checkpoint and ATM signaling promoted recovery of normal human cells after low-dose FA. Our results revealed a major role of the KAT5-ATM axis in protection of replicating chromatin against damage by the endogenous carcinogen FA. PMID:26420831

Histochemical Demonstration of Protein-Bound Alpha-Acylamido Carboxyl Groups

PubMed Central

Barrnett, Russell J.; Seligman, Arnold M.

1958-01-01

A method has been developed to demonstrate the alpha-acylamido carboxyl groups of protein, taking advantage of the fact that acylamido carboxyl groups are converted to ketonic carbonyls by the action of acetic anhydride and absolute pyridine. The method utilizes deparaffinized sections of tissues fixed in a variety of fixatives. Following the conversion of carboxyls to the methyl ketones, the latter are stained with 2-hydroxy-3-naphthoic acid hydrazide. Control experiments have indicated that methylation of carboxyls prevented staining, as did carbonyl reagents after the carboxyls were transformed to methyl ketones. Leucofuchsin did not stain the ketonic carbonyls, and only elastic tissue stained with 2-hydroxy-3-naphthoic acid hydrazide without the previous use of the catalyzed reaction with anhydride. A brief survey of the reaction on various tissues of the albino rat was made, and the effects of various fixatives were assayed. Of particular interest were certain sites, such as acidophiles of the anterior pituitary gland, where an intense reaction occurred. The possibility exists that certain specific proteins rich in terminal acylamido carboxyl groups, by virtue of their protein side chains or low molecular weight, may be demonstrated by this method. PMID:13525430

Antibacterial properties of 3 H-spiro[1-benzofuran-2,1'-cyclohexane] derivatives from Heliotropium filifolium.

PubMed

Urzúa, Alejandro; Echeverría, Javier; Rezende, Marcos C; Wilkens, Marcela

2008-10-01

A re-examination of cuticular components of Heliotropium filifolium allowed the isolation of four new compounds: 3'-hydroxy-2',2',6'-trimethyl-3H-spiro[1-benzo-furan-2,1'-cyclohexane]-5-carboxylic acid(2), methyl 3'-acetyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (3), methyl 3'-isopentanoyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (4) and methyl 3'-benzoyloxy-2',2',6'-trimethyl-3H-spiro[1-benzofuran-2,1'-cyclohexane]-5-carboxylate (5).Compounds 2-5 were identified by their spectroscopic analogies with filifolinol (1), and their structures confirmed by chemical correlation with 1. The antimicrobial properties of the compounds were tested against Gram positive and Gram negative bacteria. Some of them proved to be active against Gram positive, but inactive against Gram negative bacteria. In searching for structure-activity relationships from the obtained MIC values, lipophilicity was shown to be an important variable.

Synthesis of furan-3-carboxylic and 4-methylene-4,5-dihydrofuran-3-carboxylic esters by direct palladium iodide catalyzed oxidative carbonylation of 3-yne-1,2-diol derivatives.

PubMed

Gabriele, Bartolo; Mancuso, Raffaella; Maltese, Vito; Veltri, Lucia; Salerno, Giuseppe

2012-10-05

A variety of 3-yne-1,2-diol derivatives 1, bearing a primary or secondary alcoholic group at C-1, have been efficiently converted into high value added furan-3-carboxylic esters 2 in one step by PdI(2)/KI-catalyzed direct oxidative carbonylation, carried out in alcoholic media under relatively mild conditions (100 °C under 40 atm of a 4/1 mixture of CO and air). Carbonylated furans 2 were obtained in fair to excellent isolated yields (56-93%) through a sequential 5-endo-dig heterocyclization-alkoxycarbonylation-dehydration process, using only oxygen as the external oxidant. Under similar conditions, 2-methyl-3-yne-1,2-diols 3, bearing a tertiary alcoholic group, afforded 4-methylene-4,5-dihydrofuran-3-carboxylates 4 in satisfactory yields (58-70%).

Carboxylate modified porous graphitic carbon: a new class of hydrophilic interaction liquid chromatography phases.

PubMed

Wahab, M Farooq; Ibrahim, Mohammed E A; Lucy, Charles A

2013-06-18

Stationary phases for hydrophilic interaction liquid chromatography (HILIC) are predominantly based on silica and polymer supports. We present porous graphitic carbon particles with covalently attached carboxylic acid groups (carboxylate-PGC) as a new HILIC stationary phase. PGC particles were modified by adsorbing the diazonium salt of 4-aminobenzoic acid onto the PGC, followed by reduction of the adsorbed salt with sodium borohydride. The newly developed carboxylate-PGC phase exhibits different selectivity than that of 35 HPLC columns, including bare silica, zwitterionic, amine, reversed, and unmodified PGC phases. Carboxylate-PGC is stable from pH 2.0 to 12.6, yielding reproducible retention even at pH 12.6. Characterization of the new phase is presented by X-ray photoelectron spectroscopy, thermogravimetry, zeta potentials, and elemental analysis. The chromatographic performance of carboxylate-PGC as a HILIC phase is illustrated by separations of carboxylic acids, nucleotides, phenols, and amino acids.

Evaluation of apoptosis indexes in currently used oral alpha- blockers in prostate: a pilot study

PubMed Central

Demir, Mehmet; Akin, Yigit; Terim, Kubra Asena Kapakin; Gulum, Mehmet; Buyukfirat, Evren; Ciftci, Halil; Yeni, Ercan

2018-01-01

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis. PMID:29617082

Hypertension: renin-angiotensin-aldosterone system alterations.

PubMed

Te Riet, Luuk; van Esch, Joep H M; Roks, Anton J M; van den Meiracker, Anton H; Danser, A H Jan

2015-03-13

Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension. © 2015 American Heart Association, Inc.

Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study.

PubMed

Demir, Mehmet; Akin, Yigit; Terim, Kubra Asena Kapakin; Gulum, Mehmet; Buyukfirat, Evren; Ciftci, Halil; Yeni, Ercan

2018-01-01

Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Patients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analysis in Java were used for evaluations. Statistical significant p was p<0.05. There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statistical significant difference apoptosis index in immunochemical TUNEL dyeing and image software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis. Copyright® by the International Brazilian Journal of Urology.

Supramolecular architectures in the salt trimethoprimium ferrocene-1-carboxylate and the cocrystal 4-amino-5-chloro-2,6-dimethylpyrimidine-ferrocene-1-carboxylic acid (1/1).

PubMed

Swinton Darious, Robert; Thomas Muthiah, Packianathan; Perdih, Franc

2017-09-01

In the salt trimethoprimium ferrocenecarboxylate [systematic name: 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium ferrocene-1-carboxylate], (C 14 H 19 N 4 O 3 )[Fe(C 5 H 5 )(C 6 H 4 O 2 )], (I), of the antibacterial compound trimethoprim, the carboxylate group interacts with the protonated aminopyrimidine group of trimethoprim via two N-H...O hydrogen bonds, generating a robust R 2 2 (8) ring motif (heterosynthon). However, in the cocrystal 4-amino-5-chloro-2,6-dimethylpyrimidine-ferrocene-1-carboxylic acid (1/1), [Fe(C 5 H 5 )(C 6 H 5 O 2 )]·C 6 H 8 ClN 3 , (II), the carboxyl-aminopyrimidine interaction [R 2 2 (8) motif] is absent. The carboxyl group interacts with the pyrimidine ring via a single O-H...N hydrogen bond. The pyrimidine rings, however, form base pairs via a pair of N-H...N hydrogen bonds, generating an R 2 2 (8) supramolecular homosynthon. In salt (I), the unsubstituted cyclopentadienyl ring is disordered over two positions, with a refined site-occupation ratio of 0.573 (10):0.427 (10). In this study, the two five-membered cyclopentadienyl (Cp) rings of ferrocene are in a staggered conformation, as is evident from the C...Cg...Cg...C pseudo-torsion angles, which are in the range 36.13-37.53° for (I) and 22.58-23.46° for (II). Regarding the Cp ring of the minor component in salt (I), the geometry of the ferrocene ring is in an eclipsed conformation, as is evident from the C...Cg...Cg...C pseudo-torsion angles, which are in the range 79.26-80.94°. Both crystal structures are further stabilized by weak π-π interactions.

Poly[[nona­aqua­bis­(μ-5-hy­droxy­benzene-1,3-di­carboxyl­ato)(5-hy­droxy­benzene-1,3-di­carboxyl­ato)dicerium(III)] hexa­hydrate

PubMed Central

Fan, Xiao; Daiguebonne, Carole; Guillou, Olivier; Camara, Magatte

2014-01-01

In the title coordination polymer, {[Ce2(C8H4O5)3(H2O)9]·6H2O}n, the asymmetric unit is formed by two CeIII atoms, three 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligands, nine coordinating water mol­ecules and six water mol­ecules of crystallization. The two CeIII atoms are bridged by 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligands acting in a bis-bidentate coordination mode, generating infinite chains along [101]. Both independent metal atoms are nine-coordinated, one by four O atoms from the carboxyl­ate groups of two bridging 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligands and five O atoms from water mol­ecules, generating a tricapped trigonal–prismatic geometry. The coordination around the second CeIII atom is similar, except that one of the water mol­ecules is replaced by an O atom from an additional 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligand acting in a monodentate coordination mode and forming a capped square-anti­prismatic geometry. PMID:24860313

Two isomeric lead(II) carboxylate-phosphonates: syntheses, crystal structures and characterizations

NASA Astrophysics Data System (ADS)

Lei, Chong; Mao, Jiang-Gao; Sun, Yan-Qiong

2004-07-01

Two isomeric layered lead(II) carboxylate-phosphonates of N-(phosphonomethyl)- N-methyl glycine ([MeN(CH 2CO 2H)(CH 2PO 3H 2)]=H 3L), namely, monoclinic Pb 3L 2·H 2O 1 and triclinic Pb 3L 2·H 2O 2, have been synthesized and structurally determined. Compound 1 synthesized by hydrothermal reaction at 150°C is monoclinic, space group C2/ c with a=19.9872(6), b=11.9333(1) and c=15.8399(4) Å, β=110.432(3)°, V=3540.3(1) Å 3, and Z=8. The structure of compound 1 features a <400> layer in which the lead(II) ions are bridged by both phosphonate and carboxylate groups. The lattice water molecules are located between the layers, forming hydrogen bonds with the non-coordinated carboxylate oxygen atoms. Compound 2 with a same empirical formula as compound 1 was synthesized by hydrothermal reaction at 170°C. It has a different layer structure from that of compound 1 due to the adoption of a different coordination mode for the ligand. It crystallizes in the triclinic system, space group P 1¯ with cell parameters of a=7.1370(6), b=11.522(1), c=11.950(1) Å, α=110.280(2), β=91.625(2), γ=95.614(2)°, V=915.3(1) Å 3 and Z=2. The structure of compound 2 features a <020> metal carboxylate-phosphonate double layer built from 1D lead(II) carboxylate chains interconnected with 1D lead(II) phosphonate double chains. XRD powder patterns of compounds 1 and 2 indicate that each compound exists as a single phase.

Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures.

PubMed

Zareie, Parisa; Sadegh, Mehdi; Palizvan, Mohammad Reza; Moradi-Chameh, Homeira

2018-06-01

2-Arachidonoylglycerol (2-AG) and anandamide are two major endocannabinoids produced, released and eliminated by metabolic pathways. Anticonvulsive effect of 2-AG and CB1 receptor is well-established. Herein, we designed to investigate the anticonvulsive influence of key components of the 2-AG and anandamide metabolism. Tonic-clonic seizures were induced by an injection of Pentylenetetrazol (80 mg/kg, i.p.) in adult male Wistar rats. Delay and duration for the seizure stages were considered for analysis. Monoacylglycerol lipase blocker (JJKK048; 1 mg/kg) or alpha/beta hydroxylase domain 6 blocker (WWL70; 5 mg/kg) were administrated alone or with 2-AG to evaluate the anticonvulsive potential of these enzymes. To determine the CB1 receptor involvement, its blocker (MJ15; 3 mg/kg) was administrated associated with JJKK048 or WWL70. To assess anandamide anticonvulsive effect, anandamide membrane transporter blocker (LY21813240; 2.5 mg/kg) was used alone or associated with MJ15. Also, fatty acid amide hydrolase blocker (URB597; 1 mg/kg; to prevent intracellular anandamide hydrolysis) were used alone or with AMG21629 (transient receptor potential vanilloid; TRPV1 antagonist; 3 mg/kg). All compounds were dissolved in DMSO and injected i.p., before the Pentylenetetrazol. Both JJKK048 and WWL70 revealed anticonvulsive effect. Anticonvulsive effect of JJKK048 but not WWL70 was CB1 receptor dependent. LY2183240 showed CB1 receptor dependent anticonvulsive effect. However, URB597 revealed a TRPV1 dependent proconvulsive effect. It seems extracellular accumulation of 2-AG or anandamide has anticonvulsive effect through the CB1 receptor, while intracellular anandamide accumulation is proconvulsive through TRPV1.

Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation

PubMed Central

Nagahama, Masahiro; Morimitsu, Shinsuke; Kihara, Atsushi; Akita, Masahiko; Setsu, Koujun; Sakurai, Jun

2003-01-01

Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. Tachykinin NK1 receptor antagonists, [D-Pro2, D-Trp7,9]-SP, [D-Pro4, D-Trp7,9]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK1 receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP8-37). The toxin-induced leakage was significantly inhibited by the N-type Ca2+ channel blocker, ω-conotoxin MVIIA, and the bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), but was not affected by the selective L-type Ca2+ channel blocker, verapamil, the P-type Ca2+ channel blocker, ω-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na+ channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK1 receptors. PMID:12522069

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia.

PubMed

Kawahara, Takashi; Morita, Satoshi; Ito, Hiroki; Terao, Hideyuki; Sakata, Ryoko; Ishiguro, Hitoshi; Tanaka, Katsuyuki; Miyamoto, Hiroshi; Matsuzaki, Junichi; Kubota, Yoshinobu; Uemura, Hiroji

2013-06-12

Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.

Influence of phosphocholine alkyl chain length on peptide-micelle interactions and micellar size and shape.

PubMed

Göbl, Christoph; Dulle, Martin; Hohlweg, Walter; Grossauer, Jörg; Falsone, S Fabio; Glatter, Otto; Zangger, Klaus

2010-04-08

The interaction with biological membranes is of functional importance for many peptides and proteins. Structural studies on such membrane-bound biomacromolecules are often carried out in solutions containing small membrane-mimetic assemblies of detergent molecules. To investigate the influence of the hydrophobic chain length on the structure, diffusional and dynamical behavior of a peptide bound to micelles, we studied the binding of three peptides to n-phosphocholines with n ranging from 8 to 16. The peptides studied are the 15 residue antimicrobial peptide CM15, the 25-residue transmembrane helix 7 of yeast V-ATPase (TM7), and the 35-residue bacterial toxin LdrD. To keep the dimension of the peptide-membrane-mimetic assembly small, micelles are typically used when studying membrane-bound peptides and proteins, for example, by solution NMR spectroscopy. Since they are readily available in deuterated form most often sodium-dodecylsulfate (SDS) and dodecylphosphocholine (DPC) are used as the micelle-forming detergent. Using NMR, CD, and SAXS, we found that all phosphocholines studied form spherical micelles in the presence and absence of small bound peptides and the diameters of the micelles are basically unchanged upon peptide binding. The size of the peptide relative to the micelle determines to what extent the secondary structure can form. For small peptides (up to approximately 25 residues) the use of shorter chain phosphocholines is recommended for solution NMR studies due to the favorable spectral quality and since they are as well-structured as in DPC. In contrast, larger peptides are better structured in micelles formed by detergents with chain lengths longer than DPC.

Crystal structure of fac-aquatricarbonyl[(S)-valin-ato-κ(2) N,O]-rhenium(I).

PubMed

Piletska, Kseniia O; Domasevitch, Kostiantyn V; Shtemenko, Alexander V

2016-04-01

In the mol-ecule of the title compound, [Re(C5H10NO2)(CO)3(H2O)], the Re(I) atom adopts a distorted octa-hedral coordination sphere defined by one aqua and three carbonyl ligands as well as one amino N and one carboxyl-ate O atom of the chelating valinate anion. The carbonyl ligands are arranged in a fac-configuration around the Re(I) ion. In the crystal, an intricate hydrogen-bonding system under participation of two O-H, two N-H and one C-H donor groups and the carboxyl-ate and carbonyl O atoms as acceptor groups contribute to the formation of a three-dimensional supra-molecular network.

Beta-blockers and cardiovascular outcomes in dialysis patients: a cohort study in Ontario, Canada.

PubMed

Kitchlu, Abhijat; Clemens, Kristin; Gomes, Tara; Hackam, Daniel G; Juurlink, David N; Mamdani, Muhammad; Manno, Michael; Oliver, Matthew J; Quinn, Robert R; Suri, Rita S; Wald, Ron; Yan, Andrew T; Garg, Amit X

2012-04-01

Beta-blockers may be cardioprotective in patients receiving chronic dialysis. We examined cardiovascular outcomes among incident dialysis patients receiving beta-blocker therapy. We conducted a retrospective cohort study employing linked healthcare databases in Ontario, Canada. We studied all consecutive chronic dialysis patients aged≥66 years who initiated dialysis between 1 July 1991 and 31 July 2007. Patients were divided into three groups according to new medication use after the initiation of chronic dialysis. The three groups were patients initiated on beta-blockers, calcium channel blockers and statins only. Patients in the beta-blocker and calcium channel blocker groups could also be concurrently receiving a statin. The primary outcome was time to a composite endpoint of death, myocardial infarction, stroke or coronary revascularization. There were a total of 1836 patients (504 beta-blocker, 570 calcium channel blocker and 762 statin-only users). Compared to statin-only use, beta-blocker use was not associated with improved cardiovascular outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92-1.23]. As expected, calcium channel blocker use was also not associated with improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79-1.06). Among all subgroup analyses by beta-blocker attributes, only high-dose beta-blocker therapy was associated with better cardiovascular outcomes as compared to low-dose beta-blockers (aHR 0.50, 95% CI 0.29-0.88). We observed no beneficial effect of beta-blocker use among patients receiving chronic dialysis relative to our comparator groups. Given current uncertainty around the cardioprotective benefits of beta-blockers in patients receiving dialysis, a large randomized clinical trial is warranted.

Neither alpha-blocker therapy nor cystography is required before early catheter removal after radical prostatectomy.

PubMed

Nieder, Alan M; Manoharan, Murugesan; Kim, Sandy S; Soloway, Mark S

2005-02-01

To evaluate the success of early catheter removal from men after radical retropubic prostatectomy (RRP) without using either cystography or giving an alpha-blocker. We retrospectively analysed 156 consecutive patients who had RRPs between June 2003 and May 2004 to determine the incidence of urinary retention after early catheter removal, with no cystogram or using an alpha-blocker. The mean age of the men was 60 years and 99% were clinical stage T1 or T2; 74% had their catheters removed 8 days after RRP. The incidence of urinary retention was 1.3%, and of haematuria requiring catheter replacement 2.6%. Two patients (1.3%) developed a bladder neck contracture. In the present study removing an indwelling catheter 1 week after RRP was safe, with a minimal risk of urinary retention or bladder neck contracture. The addition of an alpha-blocker is unlikely to reduce the already low incidence of urinary retention.

Synthesis of the 1-Monoester of 2-Ketoalkanedioic Acids, e.g., Octyl α-Ketoglutarate

PubMed Central

Jung, Michael E.; Deng, Gang

2012-01-01

Oxidative cleavage of cycloalkene-1-carboxylates, made from the corresponding carboxylic acids, and subsequent oxidation of the resulting ketoaldehyde afforded the important 1-monoesters of 2-ketoalkanedioic acids. Thus ozonolysis of octyl cyclobutene-1-carboxylate followed by sodium chlorite oxidation afforded the 1-monooctyl 2-ketoglutarate. This is a cell-permeable prodrug form of α-ketoglutarate, an important intermediate in the tricarboxylic acid (TCA, Krebs) cycle and a promising therapeutic agent in its own right. PMID:23163977

Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli

PubMed Central

Åberg, Veronica; Das, Pralay; Chorell, Erik; Hedenström, Mattias; Pinkner, Jerome S.; Hultgren, Scott J.; Almqvist, Fredrik

2009-01-01

Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic E. coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here we present the synthesis and biological evaluation of carboxylic acid isosteres, including e.g. tetrazoles, acyl sulfonamides and hydroxamic acids, of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli. PMID:18499455

Photochemical Carboxylation of Activated C(sp3 )-H Bonds with CO2.

PubMed

Gui, Yong-Yuan; Zhou, Wen-Jun; Ye, Jian-Heng; Yu, Da-Gang

2017-04-10

From ugly duckling to beautiful C1: Although CO 2 may represent an ideal C1 source, it is challenging to use it as a raw material and direct carboxylation with CO 2 has mainly been confined to highly reactive species. However, recent significant breakthroughs have been made in photochemical carboxylation of challenging, un-acidic, C(sp 3 )-H bonds, including benzylic, allylic and amine C-H bonds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aromatic carboxylate effect on dimensionality of three bis(benzimidazole)-based cobalt(II) coordination polymers: Syntheses, structures and properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ju-Wen; Gong, Chun-Hua; Hou, Li-Li

2013-09-15

Three new metal-organic coordination polymers [Co(4-bbc){sub 2}(bbbm)] (1), [Co(3,5-pdc)(bbbm)]·2H{sub 2}O (2) and [Co(1,4-ndc)(bbbm)] (3) (4-Hbbc=4-bromobenzoic acid, 3,5-H{sub 2}pdc=3,5-pyridinedicarboxylic acid, 1,4-H{sub 2}ndc=1,4-naphthalenedicarboxylic acid and bbbm=1,1-(1,4-butanediyl)bis-1H-benzimidazole) were hydrothermally synthesized and structurally characterized. Polymer 1 is a 1D chain formed by the bbbm ligands and Co{sup II} ions. Polymer 2 exhibits a 2D network with a (3·4·5)(3{sup 2}·4·5·6{sup 2}·7{sup 4}) topology. Polymer 3 possesses a 3D three-fold interpenetrating framework. The versatile structures of title polymers indicate that the aromatic carboxylates have an important influence on the dimensionality of 1–3. Moreover, the thermal stability, electrochemical and luminescent properties of 1–3 were investigated. - graphicalmore » abstract: Three bis(benzimidazole)-based cobalt(II) coordination polymers tuned by aromatic carboxylates were hydrothermally synthesized and structurally characterized. The aromatic carboxylates play a key role in the dimensionality of three polymers. The electrochemical and luminescent properties of three polymers were investigated. Display Omitted - Highlights: • Three bis(benzimidazole)-based cobalt(II) coordination polymers tuned by aromatic carboxylates were obtained. • The aromatic carboxylates have an important influence on the dimensionality of three polymers. • The electrochemical and luminescent properties of three polymers were investigated.« less

Beta-blocker-induced psoriasis: a rare side effect--a case report.

PubMed

Yilmaz, Mehmet Birhan; Turhan, Hasan; Akin, Yesim; Kisacik, Halil L; Korkmaz, Sule

2002-01-01

Beta blockers are one of the oral agents shown to decrease cardiovascular morbidity and mortality rates in randomized, controlled trials, and hence, they are widely used for the management of many cardiovascular situations. In terms of side effects there are 3 major modes of action: (1) contraction of smooth muscles, particularly of bronchi with nonselective agents; (2) exaggerated cardiac effects; and (3) central nervous system effects. There are also some rare side effects of beta blockers, some of which are unpredictable, but the others are related to mode of action at the cellular level. Beta-blocking agents may cause psoriaform eruptions and worsen existing psoriasis. Psoriasis may be an inconvenient side effect of beta blockade. Herein, we report a case of beta-blocker-induced psoriasis.

A kryptoracemic salt: 2-{[2,8-bis-(tri-fluoro-meth-yl)quinolin-4-yl](hy-droxy)meth-yl}piperidin-1-ium (+)-3,3,3-tri-fluoro-2-meth-oxy-2-phenyl-propanoate.

PubMed

Wardell, James L; Wardell, Solange M S V; Tiekink, Edward R T

2016-06-01

The asymmetric unit of the title salt, C17H17F6N2O(+)·C10H8F3O3 (-), comprises two piperidin-1-ium cations and two carboxyl-ate anions. The cations, each having an l-shaped conformation owing to the near orthogonal relationship between the quinolinyl and piperidin-1-ium residues, are pseudo-enanti-omeric. The anions have the same absolute configuration but differ in the relative orientations of the carboxyl-ate, meth-oxy and benzene groups. Arguably, the most prominent difference between the anions occurs about the Cq-Om bond as seen in the Cc-Cq-Om-Cm torsion angles of -176.1 (3) and -67.1 (4)°, respectively (q = quaternary, m = meth-oxy and c = carboxyl-ate). The presence of Oh-H⋯Oc and Np-H⋯Oc hydrogen bonds leads to the formation of a supra-molecular chain along the a axis (h = hy-droxy and p = piperidin-1-ium); weak intra-molecular Np-H⋯Oh hydrogen bonds are also noted. Chains are connected into a three-dimensional architecture by C-H⋯F inter-actions. Based on a literature survey, related mol-ecules/cations adopt a uniform conformation in the solid state based on the letter L.

Effect of Amine Modification on the Properties of Zirconium-Carboxylic Acid Based Materials and Their Applications as NO2 Adsorbents at Ambient Conditions

DTIC Science & Technology

2014-01-06

as a source of –SH [23]. Nitrogen dioxide (NO2) is an acidic , corrosive , and toxic gas present in the atmosphere. The main sources of NO2 pollution is...occurring are the Lewis acid –base reactions. These reactions are facilitated by the formation of nitric Schematic reaction between the urea incorporated in...of zirconium– carboxylic acid based materials and their applications as NO2 adsorbents at ambient conditions Zirconium–carboxylic ligand-based porous

Synthesis of Side Chain Liquid Crystal Polymers by Living Ring Opening Metathesis Polymerization. 3. Influence of Molecular Weight, Interconnecting Unit and Substituent on the Mesomorphic behavior of Polymers with Laterally Attached Mesogens

DTIC Science & Technology

1992-04-08

polymethylsiloxanes, 6 -7 polyacrylates ,2,4,5 polymethacrylates, 1 ,3 and polychloroacrylates, 5 exhibit only nematic mesophases regardless of the...corresponding carboxyl chloride. Potassium bicyclo[2.2.1]hept-2-ene-5- carboxylate was prepared by titrating a methanolic solution of the carboxylic acid...Esterification of the Corresponding Benzyl Bromides. Monomers 1I-n were prepared in 47-88% yield using the following procedure. A mixture of potassium bicyclo

Contribution of KV1.5 Channel to H2O2-Induced Human Arteriolar Dilation and its Modulation by Coronary Artery Disease

PubMed Central

Nishijima, Yoshinori; Cao, Sheng; Chabowski, Dawid S.; Korishettar, Ankush; Ge, Alyce; Zheng, Xiaodong; Sparapani, Rodney; Gutterman, David D.; Zhang, David X.

2016-01-01

Rationale Hydrogen peroxide (H2O2) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating BKCa channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) as compared to those with CAD remain unknown. Objective We hypothesize that H2O2-elicited dilation involves different K+ channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease. Methods and Results H2O2 induced endothelium-independent vasodilation in non-CAD adipose arterioles, which was reduced by paxilline, a BKCa channel blocker, and by 4-AP, a KV channel blocker. Assays of mRNA transcripts, protein expression and subcellular localization revealed that KV1.5 is the major KV1 channel expressed in vascular smooth muscle cells (VSMCs) and is abundantly localized on the plasma membrane. The selective KV1.5 blocker DPO-1 and the KV1.3/1.5 blocker Psora-4 reduced H2O2-elicited dilation to a similar extent as 4-AP, but the selective KV1.3 blocker PAP-1 was without effect. In arterioles from CAD subjects, H2O2-induced dilation was significantly reduced and this dilation was inhibited by paxilline but not by 4-AP, DPO-1 or Psora-4. KV1.5 cell membrane localization and DPO-1-sensitive K+ currents were markedly reduced in isolated VSMCs from CAD arterioles, although mRNA or total cellular protein expression were largely unchanged. Conclusions In human arterioles, H2O2-induced dilation is impaired in CAD, which is associated with a transition from a combined BKCa- and KV (KV1.5)-mediated vasodilation toward a BKCa-predominant mechanism of dilation. Loss of KV1.5 vasomotor function may play an important role in microvascular dysfunction in CAD or other vascular diseases. PMID:27872049

Characterization of inhibitory anti-insulin-like growth factor receptor antibodies with different epitope specificity and ligand-blocking properties: implications for mechanism of action in vivo.

PubMed

Doern, Adam; Cao, Xianjun; Sereno, Arlene; Reyes, Christopher L; Altshuler, Angelina; Huang, Flora; Hession, Cathy; Flavier, Albert; Favis, Michael; Tran, Hon; Ailor, Eric; Levesque, Melissa; Murphy, Tracey; Berquist, Lisa; Tamraz, Susan; Snipas, Tracey; Garber, Ellen; Shestowsky, William S; Rennard, Rachel; Graff, Christilyn P; Wu, Xiufeng; Snyder, William; Cole, Lindsay; Gregson, David; Shields, Michael; Ho, Steffan N; Reff, Mitchell E; Glaser, Scott M; Dong, Jianying; Demarest, Stephen J; Hariharan, Kandasamy

2009-04-10

Therapeutic antibodies directed against the type 1 insulin-like growth factor receptor (IGF-1R) have recently gained significant momentum in the clinic because of preliminary data generated in human patients with cancer. These antibodies inhibit ligand-mediated activation of IGF-1R and the resulting down-stream signaling cascade. Here we generated a panel of antibodies against IGF-1R and screened them for their ability to block the binding of both IGF-1 and IGF-2 at escalating ligand concentrations (>1 microm) to investigate allosteric versus competitive blocking mechanisms. Four distinct inhibitory classes were found as follows: 1) allosteric IGF-1 blockers, 2) allosteric IGF-2 blockers, 3) allosteric IGF-1 and IGF-2 blockers, and 4) competitive IGF-1 and IGF-2 blockers. The epitopes of representative antibodies from each of these classes were mapped using a purified IGF-1R library containing 64 mutations. Most of these antibodies bound overlapping surfaces on the cysteine-rich repeat and L2 domains. One class of allosteric IGF-1 and IGF-2 blocker was identified that bound a separate epitope on the outer surface of the FnIII-1 domain. Using various biophysical techniques, we show that the dual IGF blockers inhibit ligand binding using a spectrum of mechanisms ranging from highly allosteric to purely competitive. Binding of IGF-1 or the inhibitory antibodies was associated with conformational changes in IGF-1R, linked to the ordering of dynamic or unstructured regions of the receptor. These results suggest IGF-1R uses disorder/order within its polypeptide sequence to regulate its activity. Interestingly, the activity of representative allosteric and competitive inhibitors on H322M tumor cell growth in vitro was reflective of their individual ligand-blocking properties. Many of the antibodies in the clinic likely adopt one of the inhibitory mechanisms described here, and the outcome of future clinical studies may reveal whether a particular inhibitory mechanism leads to optimal clinical efficacy.

Design, Synthesis, Structural and Spectroscopic Studies of Push-Pull Two-Photon Absorbing Chromophores with Acceptor Groups of Varying Strength

PubMed Central

Morales, Alma R.; Frazer, Andrew; Woodward, Adam W.; Ahn-White, Hyo-Yang; Fonari, Alexandr; Tongwa, Paul; Timofeeva, Tatiana; Belfield, Kevin D.

2013-01-01

A new series of unsymmetrical diphenylaminofluorene-based chromophores with various strong π-electron acceptors were synthesized and fully characterized. The systematic alteration of the structural design facilitated the investigation of effects such as molecular symmetry and strength of electron-donating and/or withdrawing termini have on optical nonlinearity. In order to determine the electronic and geometrical properties of the novel compounds, a thorough investigation was carried out by a combination of linear and nonlinear spectroscopic techniques, single crystal X-ray diffraction, and quantum chemical calculations. Finally, on the basis of two-photon absorption (2PA) cross sections, the general trend for π -electron accepting ability, i.e., ability to accept charge transfer from diphenylamine was: 2-pyran-4-ylidene malononitrile (pyranone) > dicyanovinyl > bis(dicyanomethylidene)indane > 1-(thiophen-2-yl)propenone > dicyanoethylenyl > 3-(thiophen-2-yl)propenone. An analog with the 2-pyran-4-ylidene malononitrile acceptor group exhibited a nearly three-fold enhancement of the 2PA< δ (1650 GM at 840 nm), relative to other members of the series. PMID:23305555

Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non‐obese volunteers

PubMed Central

Chairat, Kalayanee; Jittamala, Podjanee; Hanpithakpong, Warunee; Day, Nicholas P. J.; White, Nicholas J.; Pukrittayakamee, Sasithon

2016-01-01

Aims The aims of the present study were to compare the pharmacokinetics of oseltamivir and its active antiviral metabolite oseltamivir carboxylate in obese and non‐obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and oseltamivir carboxylate. Methods The population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese [body mass index (BMI) ≥30 kg m−2) and 12 non‐obese (BMI <30 kg m−2) Thai adult volunteers receiving a standard dose of 75 mg and a double dose of 150 mg in a randomized sequence. Concentration–time data were collected and analysed using nonlinear mixed‐effects modelling. Results The pharmacokinetics of oseltamivir and oseltamivir carboxylate were described simultaneously by first‐order absorption, with a one‐compartment disposition model for oseltamivir, followed by a metabolism compartment and a one‐compartment disposition model for oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance {3.84% increase for each 10 ml min−1 increase in creatinine clearance [95% confidence interval (CI) 0.178%, 8.02%]}. Obese individuals had an approximately 25% (95% CI 24%, 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI 19%, 23%) and 10% higher oseltamivir carboxylate clearance (95% CI 9%, 11%) compared with non‐obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate. Conclusions The results confirmed that a dose adjustment for oseltamivir in obese individuals is not necessary on the basis of its pharmacokinetics. PMID:26810861

A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

PubMed

Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

A Low-Dose β1-Blocker in Combination with Milrinone Improves Intracellular Ca2+ Handling in Failing Cardiomyocytes by Inhibition of Milrinone-Induced Diastolic Ca2+ Leakage from the Sarcoplasmic Reticulum

PubMed Central

Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

Objectives The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. Background The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca2+ handling in heart failure remains unclear. Methods We investigated the effect of milrinone plus landiolol on intracellular Ca2+ transient (CaT), cell shortening (CS), the frequency of diastolic Ca2+ sparks (CaSF), and sarcoplasmic reticulum Ca2+ concentration ({Ca2+}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). Results In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. Conclusion A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca2+ leak. PMID:25614983

Activation of Acetone and Other Simple Ketones in Anaerobic Bacteria.

PubMed

Heider, Johann; Schühle, Karola; Frey, Jasmin; Schink, Bernhard

2016-01-01

Acetone and other ketones are activated for subsequent degradation through carboxylation by many nitrate-reducing, phototrophic, and obligately aerobic bacteria. Acetone carboxylation leads to acetoacetate, which is subsequently activated to a thioester and degraded via thiolysis. Two different types of acetone carboxylases have been described, which require either 2 or 4 ATP equivalents as an energy supply for the carboxylation reaction. Both enzymes appear to combine acetone enolphosphate with carbonic phosphate to form acetoacetate. A similar but more complex enzyme is known to carboxylate the aromatic ketone acetophenone, a metabolic intermediate in anaerobic ethylbenzene metabolism in denitrifying bacteria, with simultaneous hydrolysis of 2 ATP to 2 ADP. Obligately anaerobic sulfate-reducing bacteria activate acetone to a four-carbon compound as well, but via a different process than bicarbonate- or CO2-dependent carboxylation. The present evidence indicates that either carbon monoxide or a formyl residue is used as a cosubstrate, and that the overall ATP expenditure of this pathway is substantially lower than in the known acetone carboxylase reactions. © 2016 S. Karger AG, Basel.

Excitation of Bloch surface wave on tapered fiber coated with one-dimensional photonic crystal for refractive index sensing.

PubMed

Tu, Tianyu; Pang, Fufei; Zhu, Shan; Cheng, Jiajing; Liu, Huanhuan; Wen, Jianxiang; Wang, Tingyun

2017-04-17

We have theoretically and experimentally demonstrated a novel approach to excite Bloch surface wave (BSW) on tapered optical fibers, which are coated with one-dimensional photonic crystal (1DPC) consisting of periodic TiO₂ and Al₂O₃ by atomic layer deposition technology. Two resonant dips are found in transmission spectra that are originated from the excitation of BSW for p-polarized light and s-polarized light, respectively. For the first time, we have demonstrated the developed device for refractive index (RI) sensing.

Characterization of silicon carbide and diamond detectors for neutron applications

NASA Astrophysics Data System (ADS)

Hodgson, M.; Lohstroh, A.; Sellin, P.; Thomas, D.

2017-10-01

The presence of carbon atoms in silicon carbide and diamond makes these materials ideal candidates for direct fast neutron detectors. Furthermore the low atomic number, strong covalent bonds, high displacement energies, wide bandgap and low intrinsic carrier concentrations make these semiconductor detectors potentially suitable for applications where rugged, high-temperature, low-gamma-sensitivity detectors are required, such as active interrogation, electronic personal neutron dosimetry and harsh environment detectors. A thorough direct performance comparison of the detection capabilities of semi-insulating silicon carbide (SiC-SI), single crystal diamond (D-SC), polycrystalline diamond (D-PC) and a self-biased epitaxial silicon carbide (SiC-EP) detector has been conducted and benchmarked against a commercial silicon PIN (Si-PIN) diode, in a wide range of alpha (Am-241), beta (Sr/Y-90), ionizing photon (65 keV to 1332 keV) and neutron radiation fields (including 1.2 MeV to 16.5 MeV mono-energetic neutrons, as well as neutrons from AmBe and Cf-252 sources). All detectors were shown to be able to directly detect and distinguish both the different radiation types and energies by using a simple energy threshold discrimination method. The SiC devices demonstrated the best neutron energy discrimination ratio (E\\max (n=5 MeV)/E\\max (n=1 MeV)  ≈5), whereas a superior neutron/photon cross-sensitivity ratio was observed in the D-PC detector (E\\max (AmBe)/E\\max (Co-60)  ≈16). Further work also demonstrated that the cross-sensitivity ratios can be improved through use of a simple proton-recoil conversion layer. Stability issues were also observed in the D-SC, D-PC and SiC-SI detectors while under irradiation, namely a change of energy peak position and/or count rate with time (often referred to as the polarization effect). This phenomenon within the detectors was non-debilitating over the time period tested (> 5 h) and, as such, stable operation was possible. Furthermore, the D-SC, self-biased SiC-EP and semi-insulating SiC detectors were shown to operate over the temperature range -60 °C to +100 °C.

Decreased Mortality With Beta-Blockers in Patients With Heart Failure and Coexisting Atrial Fibrillation: An AF-CHF Substudy.

PubMed

Cadrin-Tourigny, Julia; Shohoudi, Azadeh; Roy, Denis; Talajic, Mario; Tadros, Rafik; Mondésert, Blandine; Dyrda, Katia; Rivard, Léna; Andrade, Jason G; Macle, Laurent; Guerra, Peter G; Thibault, Bernard; Dubuc, Marc; Khairy, Paul

2017-02-01

The impact of beta-blockers on mortality and hospitalizations was assessed in the largest randomized trial of patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF): the Atrial Fibrillation-Congestive Heart Failure trial. Although beta-blockers are the cornerstone of therapy for HFrEF, a recent patient-level meta-analysis cast doubt on their efficacy in patients with coexisting AF. From a total of 1,376 subjects randomized in the AF-CHF trial, those without beta-blockers at baseline were propensity matched to a maximum of 2 exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate. Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular ejection fraction 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR]: 0.721, 95% confidence interval [CI]: 0.549 to 0.945; p = 0.0180) but not hospitalizations (HR: 0.886; 95% CI: 0.715 to 1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR: 0.668 for all-cause mortality; 95% CI: 0.511 to 0.874; p = 0.0032; HR: 0.814 for hospitalizations; 95% CI: 0.653 to 1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations. In propensity-matched analyses, beta-blockers were associated with significantly lower mortality but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF. These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Characterization and diagenesis of strong-acid carboxyl groups in humic substances

USGS Publications Warehouse

Leenheer, J.A.; Wershaw, R. L.; Brown, G.K.; Reddy, M.M.

2003-01-01

A small fraction of carboxylic acid functional groups in humic substances are exceptionally acidic with pKa values as low as 0.5. A review of acid-group theory eliminated most models and explanations for these exceptionally acidic carboxyl groups. These acidic carboxyl groups in Suwannee River fulvic acid were enriched by a 2-stage fractionation process and the fractions were characterized by elemental, molecular-weight, and titrimetric analyses, and by infrared and 13C- and 1H-nuclear magnetic resonance spectrometry. An average structural model of the most acidic fraction derived from the characterization data indicated a high density of carboxyl groups clustered on oxygen-heterocycle alicyclic rings. Intramolecular H-bonding between adjacent carboxyl groups in these ring structures enhanced stabilization of the carboxylate anion which results in low pKa1 values. The standard, tetrahydrofuran tetracarboxylic acid, was shown to have similar acidity characteristics to the highly acidic fulvic acid fraction. The end products of 3 known diagenetic pathways for the formation of humic substances were shown to result in carboxyl groups clustered on oxygen-heterocycle alicyclic rings.

The effect of the physical activity on polymorphic premature ventricular complexes in chronic kidney disease.

PubMed

Kiuchi, Márcio G; Chen, Shaojie

2017-06-01

Polymorphic premature ventricular complexes (PVCs) are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Endurance exercise training clearly lowers sympathetic activity in sympatho-excitatory disease states and may be tolerated by patients with chronic kidney disease (CKD). We assessed 40 CKD patients with hypertension with polymorphic PVCs. Patients underwent a complete medical history and physical examination. We evaluated the effectiveness of β blocker only or β blocker + exercise during 12 months of follow-up regarding the changes of the numbers of PVCs and mean heart rate (HR) by 24-hour-Holter. We observed in the β blocker group a significant decrease in the number of polymorphic PVCs from baseline 36,515 ± 3,518 to 3, 6, 9 and 12 months of follow-up, 28,314 ± 2,938, 23,709 ± 1,846, 22,564 ± 1,673, and 22,725 ± 1,415, respectively ( P < 0.001). In the β blocker + exercise group a significant decrease in the number of polymorphic PVCs also occurred from baseline 36,091 ± 3,327 to 3, 6, 9 and 12 months of follow-up, 29,252 ± 3,211, 20,948 ± 2,386, 14,238 ± 3,338, and 6,225 ± 2,319, respectively ( P < 0.001). Comparisons between the two groups at the same time point showed differences from the sixth month onwards: the 6th (Δ = -2,761, P = 0.045), 9th (Δ = -8,325, P < 0.001) and 12th (Δ = -16,500, P < 0.001) months. There was an improvement during the 12 months of follow-up vs. baseline, after the β blocker or β blocker + exercise in mean 24-hour HR Holter monitoring, creatinine values, eGFR, and ACR. Polymorphic PVCs may be modifiable by physical activity in CKD patients with hypertension without structural heart disease.

Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases.

PubMed

Vergidis, Paschalis; Avery, Robin K; Wheat, L Joseph; Dotson, Jennifer L; Assi, Maha A; Antoun, Smyrna A; Hamoud, Kassem A; Burdette, Steven D; Freifeld, Alison G; McKinsey, David S; Money, Mary E; Myint, Thein; Andes, David R; Hoey, Cynthia A; Kaul, Daniel A; Dickter, Jana K; Liebers, David E; Miller, Rachel A; Muth, William E; Prakash, Vidhya; Steiner, Frederick T; Walker, Randall C; Hage, Chadi A

2015-08-01

Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A reliable and economical method for gaining mouse embryonic fibroblasts capable of preparing feeder layers.

PubMed

Jiang, Guangming; Wan, Xiaoju; Wang, Ming; Zhou, Jianhua; Pan, Jian; Wang, Baolong

2016-08-01

Mouse embryonic fibroblasts (MEFs) are widely used to prepare feeder layers for culturing embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in vitro. Transportation lesions and exorbitant prices make the commercially obtained MEFs unsuitable for long term research. The aim of present study is to establish a method, which enables researchers to gain MEFs from mice and establish feeder layers by themselves in ordinary laboratories. MEFs were isolated from ICR mouse embryos at 12.5-17.5 day post-coitum (DPC) and cultured in vitro. At P2-P7, the cells were inactivated with mitomycin C or by X-ray irradiation. Then they were used to prepare feeder layers. The key factors of the whole protocol were analyzed to determine the optimal conditions for the method. The results revealed MEFs isolated at 12.5-13.5 DPC, and cultured to P3 were the best choice for feeder preparation, those P2 and P4-P5 MEFs were also suitable for the purpose. The P3-P5 MEFs treated with 10 μg/ml of mitomycin C for 3 h, or irradiated with X-ray at 1.5 Gy/min for 25 Gy were the most suitable feeder cells. Treating MEFs with 10 μg/ml of mitomycin C for 2.5 h, 15 μg/ml for 2.0 h, or irradiating the cells with 20 Gy of X-ray at 2.0 Gy/min could all serve as alternative methods for P3-P4 cells. Our study provides a reliable and economical way to obtain large amount of qualified MEFs for long term research of ESCs or iPSCs.

Diuretic or Beta-Blocker for Hypertensive Patients Already Receiving ACEI/ARB and Calcium Channel Blocker.

PubMed

Tsai, Min-Shan; Tang, Chao-Hsiun; Lin, Chia-Ying; Chuang, Po-Ya; Chen, Nai-Chuan; Huang, Chien-Hua; Chang, Wei-Tien; Wang, Tzung-Dau; Yu, Ping-Hsun; Chen, Wen-Jone

2017-12-01

In patients already receiving combination of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), whether the choice of additional diuretic or beta-blocker affects the cardiovascular and cerebrovascular outcomes remains unclear. A total of 13,551 patients who were concurrently receiving three anti-hypertensive agents of different classes through outpatient clinics during 2004-2006 were identified from the National Health Insurance Research Database of Taiwan. Patients were further classified into two treatment groups according to the medication possession ratio of drug combinations; the A + B + C group as those who received concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of stroke, acute myocardial infarction (AMI), mortality, and major adverse cardiovascular events (MACE) between the two treatment groups was investigated. After propensity score matching, there were 5120 patients in each group. There were no differences in the incidence of cardiovascular events between the two groups. In patients with prior history of cerebrovascular accident (CVA), the A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56; 95% CI 1.051-2.307; p < 0.05) as compared with the A + B + C group. Adding a diuretic may be better than adding a beta-blocker for treating hypertensive patients with prior CVA history who have already received ACEIs/ARBs and CCBs.

Beta-blocker use and risk of symptomatic bradyarrhythmias: a hospital-based case-control study.

PubMed

Lu, Hou Tee; Kam, Jiyen; Nordin, Rusli Bin; Khelae, Surinder Kaur; Wang, Jing Mein; Choy, Chun Ngok; Lee, Chuey Yan

2016-09-01

To investigate the risk factors of symptomatic bradyarrhythmias in relation to β-blockers use. A hospital-based case-control study [228 patients: 108 with symptomatic bradyarrhythmias (cases) and 120 controls] was conducted in Sultanah Aminah Hospital, Malaysia between January 2011 and January 2014. The mean age was 61.1 ± 13.3 years with a majority of men (68.9%). Cases were likely than control to be older, hypertensive, lower body mass index and concomitant use of rate-controlling drugs (such as digoxin, verapamil, diltiazem, ivabradine or amiodarone). Significantly higher level of serum potassium, urea, creatinine and lower level of estimated glomerular filtration rate (eGFR) were observed among cases as compared to controls. On univariate analysis among patients on β-blockers, older age (crude OR: 1.07; 95% CI: 1.03-1.11, P = 0.000), hypertension (crude OR: 5.6; 95% CI: 1.51-20.72, P = 0.010), lower sodium (crude OR: 0.04; 95% CI: 0.81-0.99, P = 0.036), higher potassium (crude OR: 2.36; 95% CI: 1.31-4.26, P = 0.004) and higher urea (crude OR: 1.23; 95% CI: 1.11-1.38, P = 0.000) were associated with increased risk of symptomatic bradyarrhythmias; eGFR was inversely and significantly associated with symptomatic bradyarrhythmias in both 'β-blockers' (crude OR: 0.97; 95% CI: 0.96-0.98, P = 0.000) and 'non-β-blockers' (crude OR: 0.99; 95% CI: 0.97-0.99, P = 0.023) arms. However, eGFR was not significantly associated with symptomatic bradyarrhythmias in the final model of both 'β-blockers' (adjusted OR: 0.98; 95% CI: 0.96-0.98, P = 0.103) and 'non-β-blockers' (adjusted OR: 0.99; 95% CI: 0.97-1.01, P = 0.328) arms. Importantly, older age was a significant predictor of symptomatic bradyarrhythmias in the 'β-blockers' as compared to the 'non-β-blockers' arms (adjusted OR: 1.09; 95% CI: 1.03-1.15, P = 0.003 vs . adjusted OR: 1.03; 95% CI: 0.98-1.09, P = 0.232, respectively). Older age was a significant predictor of symptomatic bradyarrhythmias in patients on β-blockers than those without β-blockers.

Measurement of Endogenous versus Exogenous Formaldehyde-Induced DNA-Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry.

PubMed

Lai, Yongquan; Yu, Rui; Hartwell, Hadley J; Moeller, Benjamin C; Bodnar, Wanda M; Swenberg, James A

2016-05-01

DNA-protein crosslinks (DPC) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Because of their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([(13)CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous ((13)CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues but were absent in tissues distant to the site of contact. This observation, together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined, suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for the persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde and may inform improved disease prevention and treatment strategies. Cancer Res; 76(9); 2652-61. ©2016 AACR. ©2016 American Association for Cancer Research.

Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1,2-diol (3-MCPD).

PubMed

El Ramy, Rosy; Ould Elhkim, Mostafa; Poul, Martine; Forest, Maguelone G; Leduque, Patrick; Le Magueresse-Battistoni, Brigitte

2006-10-01

3-Monochloropropane-1,2-diol (3-MCPD) is a food-born contaminant known to display toxic effects on male reproduction, producing infertility in rats and humans. Using the rat as a model, we investigated whether or not testicular organogenesis, which, in the rat species, occurs during the second half of gestation, was at particular risk regarding 3-MCPD toxicity. Pregnant rats were given daily doses of 5, 10 or 25 mg/kg BW of 3-MCPD from days 11.5-18.5 postcoitum (dpc). On 19.5 dpc, testes were removed from fetuses for histological examination and testosterone analysis. Eight genes were selected among the differentiation markers of testicular cell lineages, and their expression was studied by RT-PCR. The levels of 3-MCPD and its main metabolite, beta-chlorolactic acid, were assayed in fetal tissues and dam plasma. Our results show a statistically significant decrease in the mean body weight gain of pregnant rats treated with 10 and 25 mg/kg BW of 3-MCPD. Fetal testes exposed to 3-MCPD exhibited normal histology and produced testosterone at levels that were similar to controls. In addition, 3-MCPD did not alter gene expression in the fetal testes. This lack of effect occurred under conditions where 3-MCPD and beta-chlorolactic acid were found to readily cross the placental barrier and diffuse throughout the fetal tissues. Our findings indicate that 3-MCPD has minimal effect on rat testicular organogenesis.

The carboxyl-terminal region of ahnak provides a link between cardiac L-type Ca2+ channels and the actin-based cytoskeleton.

PubMed

Hohaus, Annette; Person, Veronika; Behlke, Joachim; Schaper, Jutta; Morano, Ingo; Haase, Hannelore

2002-08-01

Ahnak is a ubiquitously expressed giant protein of 5643 amino acids implicated in cell differentiation and signal transduction. In a recent study, we demonstrated the association of ahnak with the regulatory beta2 subunit of the cardiac L-type Ca2+ channel. Here we identify the most carboxyl-terminal ahnak region (aa 5262-5643) to interact with recombinant beta2a as well as with beta2 and beta1a isoforms of native muscle Ca2+ channels using a panel of GST fusion proteins. Equilibrium sedimentation analysis revealed Kd values of 55 +/- 11 nM and 328 +/- 24 nM for carboxyl-terminal (aa 195-606) and amino-terminal (aa 1-200) truncates of the beta2a subunit, respectively. The same carboxyl-terminal ahnak region (aa 5262-5643) bound to G-actin and cosedimented with F-actin. Confocal microscopy of human left ventricular tissue localized the carboxyl-terminal ahnak portion to the sarcolemma including the T-tubular system and the intercalated disks of cardiomyocytes. These results suggest that ahnak provides a structural basis for the subsarcolemmal cytoarchitecture and confers the regulatory role of the actin-based cytoskeleton to the L-type Ca2+ channel.

Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia

PubMed Central

Patorno, Elisabetta; Desai, Rishi J.; Seely, Ellen W.; Mogun, Helen; Maeda, Ayumi; Fischer, Michael A.; Hernandez-Diaz, Sonia; Huybrechts, Krista F.

2016-01-01

BACKGROUND AND OBJECTIVES: β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries. METHODS: We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications. RESULTS: There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker–exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50–1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07–1.55, respectively). CONCLUSION Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia. PMID:27577580

Derivation and validation of a simple clinical risk-model in heart failure based on 6 minute walk test performance and NT-proBNP status--do we need specificity for sex and beta-blockers?

PubMed

Frankenstein, L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Nelles, M; Katus, H A; Clark, A L; Cleland, J G F; Zugck, C

2011-02-17

It is unclear whether risk prediction strategies in chronic heart failure (CHF) need to be specific for sex or beta-blockers. We examined this problem and developed and validated the consequent risk models based on 6-minute-walk-test and NT-proBNP. The derivation cohort comprised 636 German patients with systolic dysfunction. They were validated against 676 British patients with similar aetiology. ROC-curves for 1-year mortality identified cut-off values separately for specificity (none, sex, beta-blocker, both). Patients were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut-offs). Widest separation between groups was achieved with sex- and beta-blocker-specific cut offs. In the derivation population, 1-year mortality was 0%, 8%, 31% for group I, II and III, respectively. In the validation population, 1-year rates in the three risk groups were 2%, 7%, 14%, respectively, after application of the same cut-offs. Risk stratification for CHF should perhaps take sex and beta-blocker usage into account. We derived and independently validated relevant risk models based on 6-minute-walk-tests and NT-proBNP. Specifying sex and use of beta-blockers identified three distinct sub-groups with widely differing prognosis. In clinical practice, it may be appropriate to tailor the intensity of follow-up and/or the treatment strategy according to the risk-group. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Preoperative depression symptom severity and its impact on adherence to preoperative beta-blocker therapy

PubMed Central

Schonberger, Robert B.; Feinleib, Jessica; Holt, Natalie; Dai, Feng; Brandt, Cynthia; Burg, Matthew M.

2014-01-01

Objective 1) To test the association among depression symptoms, distressed personality-type, and preoperative beta-blocker non-adherence. 2) To estimate the prevalence of untreated major depression in this population. Design Prospective Observational Study Setting A Veterans hospital Patients 120 subjects on outpatient beta-blocker therapy presenting for surgery. Interventions The Patient Health Questionnaire (PHQ)-9, the D-Scale-14 (DS14), and Modified Morisky Scale (MMS) questionnaires. Measurements and Main Results Of 99 participants who presented for surgery, the incidence of preoperative non-adherence was 14.1% (95% CI 7–21%), consistent with prior research. Non-adherence was 9.5% among those with no depression, 27.8% among those with mild depression, and 28.6% among those with moderate to severe depression (Cochrane-Armitage test for trend p=0.03). Distressed personality-type was found in 35% of the cohort (95% CI 26–45%) and was not associated with beta-blocker non-adherence (Fisher’s exact p=0.24). Among participants with symptoms of Major Depressive Disorder (N=25, 25.3%), over half (N=14, 56%) had no indication of depression listed at their most recent primary care visit. Conclusions Patients with symptoms of depression on chronic beta-blocker therapy are prone to medication non-adherence on the day of surgery. The majority of surgical patients with symptoms of major depression lack a diagnosis of depression. Preoperative depression screening may thus 1) identify a population at increased risk of beta-blocker withdrawal and 2) identify patients who may benefit from anesthesiologist-initiated referral for this treatable condition. PMID:25263776

A Fate Map of the Murine Pancreas Buds Reveals a Multipotent Ventral Foregut Organ Progenitor

PubMed Central

Angelo, Jesse R.; Guerrero-Zayas, Mara-Isel; Tremblay, Kimberly D.

2012-01-01

The definitive endoderm is the embryonic germ layer that gives rise to the budding endodermal organs including the thyroid, lung, liver and pancreas as well as the remainder of the gut tube. DiI fate mapping and whole embryo culture were used to determine the endodermal origin of the 9.5 days post coitum (dpc) dorsal and ventral pancreas buds. Our results demonstrate that the progenitors of each bud occupy distinct endodermal territories. Dorsal bud progenitors are located in the medial endoderm overlying somites 2–4 between the 2 and 11 somite stage (SS). The endoderm forming the ventral pancreas bud is found in 2 distinct regions. One territory originates from the left and right lateral endoderm caudal to the anterior intestinal portal by the 6 SS and the second domain is derived from the ventral midline of the endoderm lip (VMEL). Unlike the laterally located ventral foregut progenitors, the VMEL population harbors a multipotent progenitor that contributes to the thyroid bud, the rostral cap of the liver bud, ventral midline of the liver bud and the midline of the ventral pancreas bud in a temporally restricted manner. This data suggests that the midline of the 9.5 dpc thyroid, liver and ventral pancreas buds originates from the same progenitor population, demonstrating a developmental link between all three ventral foregut buds. Taken together, these data define the location of the dorsal and ventral pancreas progenitors in the prespecified endodermal sheet and should lead to insights into the inductive events required for pancreas specification. PMID:22815796

Beta-blockers for prevention and treatment of retinopathy of prematurity in preterm infants.

PubMed

Kaempfen, Siree; Neumann, Roland P; Jost, Kerstin; Schulzke, Sven M

2018-03-02

Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the vasoproliferative retinal process, may reduce the progression of ROP or even reverse established ROP. To determine the effect of beta-blockers on short-term structural outcomes, long-term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP. We searched the Cochrane Neonatal Review Group Specialized Register; CENTRAL (in the Cochrane Library Issue 7, 2017); Embase (January 1974 to 7 August 2017); PubMed (January 1966 to 7 August 2017); and CINAHL (January 1982 to 7 August 2017). We checked references and cross-references and handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings. We considered for inclusion randomised or quasi-randomised clinical trials that used beta-blockers for prevention or treatment of ROP in preterm neonates of less than 37 weeks' gestational age. We used the standard methods of Cochrane and the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence. We included three randomised trials (N = 366) in this review. Two of these studies were at high risk of bias. All studies reported on prevention of ROP and compared oral propranolol with placebo or no treatment. We found no trials assessing beta-blockers in infants with established stage 2 or higher ROP with plus disease.In one trial, study medication was started after one week of life, i.e. prior to the first ROP screening. The other two trials included preterm infants if they had stage 2 or lower ROP without plus disease. Based on the GRADE assessment, we considered evidence to be of low quality for the following outcomes: rescue treatment with anti-VEGF or laser therapy; and arterial hypotension or bradycardia requiring inotropic support. Evidence was of moderate quality for the following outcomes: progression to stage 2 with plus disease; progression to stage 3 ROP; and progression to stage 4 or 5 ROP.Meta-analysis of three trials (N = 366) suggested beneficial effects of oral beta-blockers on the risk of requiring anti-VEGF agents (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.86; I² = 0%; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.01; I² = 75%; number needed to treat for an additional beneficial outcome (NNTB) 18, 95% CI 14 to 84) and laser therapy (typical RR 0.54, 95% CI 0.32 to 0.89; typical RD -0.09, 95% CI -0.16 to -0.02; I² = 31%; NNTB 12, 95% CI 8 to 47). Meta-analysis of two trials (N = 161) demonstrated a beneficial effect of oral beta-blockers on progression to stage 3 ROP (typical RR 0.60, 95% CI 0.37 to 0.96; I² = 0%; typical RD -0.15, 95% CI -0.28 to -0.02; I² = 73%; NNTB 7, 95% CI 5 to 67). There was no significant effect of oral beta-blockers on progression to stage 2 ROP with plus disease or to stage 4 or 5 ROP. Although meta-analysis did not indicate a significant effect of beta-blockers on arterial hypotension or bradycardia, propranolol dosage in one study was reduced by 50% in infants of less than 26 weeks' gestational age due to severe hypotension, bradycardia, and apnoea in several participants. Analyses did not indicate significant effects of beta-blockers on complications of prematurity or mortality. None of the trials reported on long-term visual impairment. Limited evidence of low-to-moderate quality suggests that prophylactic administration of oral beta-blockers might reduce progression towards stage 3 ROP and decrease the need for anti-VEGF agents or laser therapy. The clinical relevance of those findings is unclear as no data on long-term visual impairment were reported. Adverse events attributed to oral propranolol at a dose of 2 mg/kg/d raise concerns regarding systemic administration of this drug for prevention of ROP at the given dose. There is insufficient evidence to determine the efficacy and safety of beta-blockers for prevention of ROP due to high risk of bias in two included trials and the lack of long-term functional outcomes. We would encourage researchers to conduct large, well-designed trials to confirm or refute the role of beta-blockers for prevention and treatment of ROP in preterm infants. Trials should report on long-term visual impairment. Researchers should consider dose-finding studies of systemic beta-blockers and topical administration of beta-blockers, in order to optimise drug delivery and minimise adverse events.

Water-soluble Manganese and Iron Mesotetrakis(carboxyl)porphyrin: DNA Binding, Oxidative Cleavage, and Cytotoxic Activities.

PubMed

Shi, Lei; Jiang, Yi-Yu; Jiang, Tao; Yin, Wei; Yang, Jian-Ping; Cao, Man-Li; Fang, Yu-Qi; Liu, Hai-Yang

2017-06-29

Two new water-soluble metal carboxyl porphyrins, manganese (III) meso -tetrakis (carboxyl) porphyrin and iron (III) meso -tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they can strongly bind to ct-DNA via outside binding mode. Electrophoresis experiments revealed that both complexes can cleave pBR322 DNA efficiently in the presence of hydrogen peroxide, albeit 2-Mn exhibited a little higher efficiency. The inhibitor tests suggest the oxidative DNA cleavage by these two complexes may involve hydroxyl radical active intermediates. Notably, 2-Mn exhibited considerable photocytotoxicity against Hep G2 cell via triggering a significant generation of ROS and causing disruption of MMP after irradiation.

Additional Nucleophile-Free FeCl3-Catalyzed Green Deprotection of 2,4-Dimethoxyphenylmethyl-Protected Alcohols and Carboxylic Acids.

PubMed

Sawama, Yoshinari; Masuda, Masahiro; Honda, Akie; Yokoyama, Hiroki; Park, Kwihwan; Yasukawa, Naoki; Monguchi, Yasunari; Sajiki, Hironao

2016-01-01

The deprotection of the methoxyphenylmethyl (MPM) ether and ester derivatives can be generally achieved by the combinatorial use of a catalytic Lewis acid and stoichiometric nucleophile. The deprotections of 2,4-dimethoxyphenylmethyl (DMPM)-protected alcohols and carboxylic acids were found to be effectively catalyzed by iron(III) chloride without any additional nucleophile to form the deprotected mother alcohols and carboxylic acids in excellent yields. Since the present deprotection proceeds via the self-assembling mechanism of the 2,4-DMPM protective group itself to give the hardly-soluble resorcinarene derivative as a precipitate, the rigorous purification process by silica-gel column chromatography was unnecessary and the sufficiently-pure alcohols and carboxylic acids were easily obtained in satisfactory yields after simple filtration.

Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction.

PubMed

Steinman, Michael A; Zullo, Andrew R; Lee, Yoojin; Daiello, Lori A; Boscardin, W John; Dore, David D; Gan, Siqi; Fung, Kathy; Lee, Sei J; Komaiko, Kiya D R; Mor, Vincent

2017-02-01

Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit. To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older. This cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization. Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living. The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively). In contrast, little evidence of functional decline due to β-blockers was found in participants with intact cognition or mild dementia (OR, 1.03; 95% CI, 0.89-1.20; P = .03 for effect modification) or in those in the best (OR, 0.99; 95% CI, 0.77-1.26) and intermediate (OR, 1.05; 95% CI, 0.86-1.27) tertiles of functional independence (P = .06 for effect modification). Mortality benefits of β-blockers were similar across all subgroups. Use of β-blockers after AMI is associated with functional decline in older nursing home residents with substantial cognitive or functional impairment, but not in those with relatively preserved mental and functional abilities. Use of β-blockers yielded a considerable mortality benefit in all groups.

Beta-blocker use in the emergency department in patients with acute myocardial infarction undergoing primary angioplasty.

PubMed

Pancu, Diana; Lee, David C

2003-05-01

Our objectives were to evaluate the frequency of beta-blocker administration in the setting of acute myocardial infarction (AMI) where angioplasty is the primary treatment, and to investigate emergency physician's (EPs) attitudes toward beta-blockers. We performed a retrospective chart review of all patients who presented with symptoms and electrocardiogram (EKG) criteria consistent with AMI in the defined study period. Charts were reviewed for beta-blocker administration and other treatments. A survey was subsequently distributed to all EPs to determine self-reported reasons for withholding beta-blockers. There were 91 patients identified. Of those who did not have contraindications, 99% (89/90) received aspirin, 97% (88/91) received heparin, 94% (84/89) received nitrates, but only 28% (19/68) received beta-blockers. Ninety-six percent of beta-blocker-eligible patients received them as inpatients. Eighty-six percent (44/52) of EPs completed the survey. Physicians felt strongly about avoiding beta-blockers in patients with asthma exacerbation, severe congestive heart failure, and high degree AV block. Bradycardia was the most frequent reason for withholding beta-blockers. In this series of patients presenting with AMI, beta-blockers were greatly underutilized. The self-reported reasons of EPs for withholding beta-blocker therapy did not explain why 72% (49/68) of patients without contraindications did not receive beta-blockers.

Sclera-Choroid-RPE Transport of Eight β-Blockers in Human, Bovine, Porcine, Rabbit, and Rat Models

PubMed Central

Kadam, Rajendra S.; Cheruvu, Narayan P. S.; Edelhauser, Henry F.

2011-01-01

Purpose. To determine the influence of drug lipophilicity, ocular pigmentation, and species differences on transscleral solute transport. Methods. The transport of eight β-blockers across excised sclera/sclera-choroid-RPE (SCRPE) of albino rabbit, pigmented rabbit, human, porcine, and bovine eyes was determined over 6 hours. The ex vivo transscleral β-blocker transport to the vitreous at the end of 6 hours was determined in euthanatized, pigmented Brown Norway rats. The thicknesses of the sclera and SCRPE and the melanin content in choroid-RPE (CRPE) were measured to determine whether species differences in drug transport can be explained on this basis. Results. Solute lipophilicity inversely correlated with the SCRPE cumulative percentage of transport in all species (R2 ≥ 0.80). The CRPE impeded the SCRPE transport of all β-blockers (51%–64% resistance in the rabbits; 84%–99.8% in the bovine and porcine eyes) more than the sclera, with the impedance increasing with lipophilicity. SCRPE transport followed the trend albino rabbit > pigmented rabbit > human > porcine > bovine, and a cross-species comparison showed good Spearman's rho correlation (R2 ≥ 0.85). Bovine (R2 = 0.84), porcine (R2 = 0.84), and human (R2 = 0.71) SCRPE transport was more predictive than that in the rabbit models (R2 = 0.60–0.61) of transscleral solute transport to the vitreous in rats. The CRPE concentrations were higher in pigmented rabbits than in albino rabbits. The melanin content of the CRPE exhibited the trend albino rabbit ≪ pigmented rabbit < porcine ∼ bovine < rat. Normalization to scleral thickness abolished the species differences in scleral transport. Normalization to SCRPE thickness and melanin content significantly reduced species differences in SCRPE transport. Conclusions. Owing to the presence of pigment and drug binding, choroid-RPE is the principal barrier to transscleral β-blocker transport, with the barrier being more significant for lipophilic β-blockers. Although different in magnitude between species, sclera/SCRPE transport can be correlated between species. Tissue thickness accounts for the species differences in scleral transport. Differences in tissue thickness and melanin content largely account for the species differences in SCRPE transport. PMID:21282583

Year-round records of gas and particulate carboxylic acids (formate and acetate) in the boundary layer at Dumont d'Urville (coastal Antarctica): Production of carboxylic acids from biogenic NMHC emissions from the Antarctic ocean

NASA Astrophysics Data System (ADS)

Legrand, M.; Preunkert, S.; Jourdain, B.

2003-04-01

Multiple year-round concentrations of acetic and formic acids were measured both in gas and aerosol phases at Dumont d'Urville (DDU, a coastal Antarctic site: 66^o40'S, 140^o01'E) by using mist chamber and aerosol filter sampling. Aerosol levels of the 2 carboxylates range from less than one ng m-3 in winter to 5--10 ng m-3 in summer. Comparison with gas phase concentrations shows that almost 99% of the 2 carboxylic acids are present in the gas phase. Concentrations of formic acid in the gas phase are minima in June--July (70 ng m-3) and increase regularly towards summer months when levels reach ˜400 ng m-3. Concentrations of acetic acid in the gas phase exhibit a more well-marked seasonal cycle with values remaining close to 50 ng m-3 from April to October and strongly increase during summer months (mean value of 800 ng m-3). Such a strong seasonal cycle of carboxylic acids in the high southern latitude marine boundary layer displays with observations made at numerous continental sites where a more weak seasonality is generally observed. It is suggested that carboxylic acids present at DDU mainly originate from biogenic emissions from the Antarctic ocean which are expected to closely follow annual cycle of the sea ice extent and solar radiation, affecting in particular photochemical production of alkenes from dissolved organic carbon released from phytoplancton. Summer levels of carboxylic acids are discussed in terms of air-sea fluxes of NMHCs and photochemical production of carboxylic acids from ozone-alkene reactions and HO_2 reaction with peroxyacetal radical in these poor NOx environments.

The novel endomorphin degradation blockers Tyr-Pro-DClPhe-Phe-NH (EMDB-1) and Tyr-Pro-Ala-NH (EMDB-2) prolong endomorphin-2 action in rat ileum in vitro.

PubMed

Fichna, Jakub; Perlikowska, Renata; Gach, Katarzyna; do-Rego, Jean-Claude; Cravezic, Aurore; Janecka, Anna; Storr, Martin A

2010-07-01

The endogenous opioid system is involved in the control of gastrointestinal (GI) motility. The potential use of endogenous MOR ligands, endomorphins (EMs), as therapeutics is limited because of their rapid enzymatic degradation and short duration of action. Targeting enzymatic degradation is an approach to prolong EM activity. In the present study, we characterized the effects of novel blockers of EM degradation in GI tissue preparation in vitro. The effects of actinonin, diprotin A (DIP) and the novel peptide EM degradation blockers Tyr-Pro-DClPhe-Phe-NH(2) (EMDB-1), Tyr-Pro-Ala-NH(2) (EMDB-2) and Tyr-Pro-Ala-OH (EMDB-3) on EM-2-mediated inhibition of electrically induced cholinergic twitch contractions were compared in rat ileum in vitro using an organ bath. EMDB-1 and EMDB-2 significantly prolonged the inhibitory effect of EM-2 on smooth muscle contractility in rat ileum. EMDB-2 extended the EM-2 action for up to 60 min compared to 10 min in controls and was more potent than the conventional peptidase inhibitor DIP. EMDB-1 and EMDB-2 are potent EM degradation blockers, which prolong the inhibitory effects of EM-2 on smooth muscle contractility in rat ileum. These novel compounds may be of future use when targeting the endogenous opioid system in the treatment of GI motility disorders such as diarrhea.

Spectroscopic studies of transition-metal ions in molten alkali-metal carboxylates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maroni, V.A.; Maciejewski, M.L.

This paper presents the results of electronic absorption and /sup 13/C-NMR measurements on molten alkali metal formates and acetates and on solutions of selected 3d transition metal ions therein. These studies provide a unique opportunity to explore (1) the highly ordered nature of alkali carboxylates, (2) the ligand field properties of acetate and formate ions, and (3) the coordination chemistry of the 3d transition metals in molten carboxylates. 1 figure, 2 tables.

Entanglement and Bell's inequality violation above room temperature in metal carboxylates

NASA Astrophysics Data System (ADS)

Souza, A. M.; Soares-Pinto, D. O.; Sarthour, R. S.; Oliveira, I. S.; Reis, M. S.; Brandão, P.; Dos Santos, A. M.

2009-02-01

In the present work we show that a particular family of materials, the metal carboxylates, may have entangled states up to very high temperatures. From magnetic-susceptibility measurements, we have estimated the critical temperature below which entanglement exists in the copper carboxylate {Cu2(O2CH)4}{Cu(O2CH)2(2-methylpyridine)2} , and we have found this to be above room temperature (Te˜630K) . Furthermore, the results show that the system remains maximally entangled until close to ˜100K and the Bell’s inequality is violated up to nearly room temperature (˜290K) .

Entanglement and Bell's inequality violation above room temperature in metal carboxylates.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souza, A M; Soares-Pinto, D O; Sarthour, R S

In the present work we show that a particular family of materials, the metal carboxylates, may have entangled states up to very high temperatures. From magnetic-susceptibility measurements, we have estimated the critical temperature below which entanglement exists in the copper carboxylate {Cu-2(O2CH)(4)}{Cu(O2CH)(2)(2-methylpyridine)(2)}, and we have found this to be above room temperature (T-e similar to 630 K). Furthermore, the results show that the system remains maximally entangled until close to similar to 100 K and the Bell's inequality is violated up to nearly room temperature (similar to 290 K).

Ethyl 3-[1-(4-methoxy-phen-yl)-4-oxo-3-phenylazetidin-2-yl]-2-nitro-1-phenyl-2,3,10,10a-tetra-hydro-1H,5H-pyrrolo[1,2-b]isoquinoline-10a-carboxyl-ate.

PubMed

Sundaresan, S S; Ramesh, P; Arumugam, N; Raghunathan, R; Ponnuswamy, M N

2010-02-17

In the title mol-ecule, C(37)H(35)N(3)O(6), the pyrrolidine ring adopts a twist conformation and the piperidine ring is in a distorted boat conformation. One of the phenyl rings is disordered over two positions with occupancies of 0.54 (2) and 0.46 (2) and the ethyl carboxyl-ate group is also disordered over two orientations with occupancies of 0.75 (1) and 0.25 (1).

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia

PubMed Central

2013-01-01

Background Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Methods Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. Results The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Conclusions Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH. PMID:23758651

Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids

PubMed Central

2011-01-01

Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (Ki < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC50 CYP2C9 and 2C19 > 1 μM). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development. PMID:24900284

Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor

PubMed Central

Uchinoumi, Hitoshi; Yano, Masafumi; Suetomi, Takeshi; Ono, Makoto; Xu, Xiaojuan; Tateishi, Hiroki; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Kobayashi, Shigeki; Yamamoto, Takeshi; Ikeda, Yasuhiro; Ohkusa, Tomoko; Ikemoto, Noriaki; Matsuzaki, Masunori

2010-01-01

Rationale Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in a well-defined region of the cardiac type-2 ryanodine receptor (RyR2). However, the underlying mechanism by which a single mutation in such a large molecule produces drastic effects on channel function remains unresolved. Objective Using a knock-in (KI) mouse model with a human CPVT-associated RyR2 mutation (R2474S), we investigated the molecular mechanism by which CPVT is induced by a single point mutation within the RyR2. Methods and Results The R2474S/+ KI mice showed no apparent structural or histological abnormalities in the heart, but they showed clear indications of other abnormalities. Bidirectional or polymorphic VT was induced after exercise on a treadmill. The interaction between the N-terminal (aa 1–600) and central (aa 2000–2500) domains of the RyR2 (an intrinsic mechanism to close Ca2+ channels) was weakened (domain unzipping). Upon protein kinase A (PKA)-mediated phosphorylation of the RyR2, this domain unzipping further increased, resulting in a significant increase in the frequency of spontaneous Ca2+ transients. cAMP-induced aberrant Ca2+ release events (Ca2+ sparks/waves) occurred at much lower sarcoplasmic reticulum (SR) Ca2+ content as compared to the wild-type (WT). Addition of a domain-unzipping peptide, DPc10 (aa 2460–2495), to the WT reproduced the aforementioned abnormalities that are characteristic of the R2474S/+ KI mice. Addition of DPc10 to the (cAMP-treated) KI cardiomyocytes produced no further effect. Conclusions A single point mutation within the RyR2 sensitizes the channel to agonists and reduces the threshold of luminal [Ca2+] for activation, primarily mediated by defective inter-domain interaction within the RyR2. PMID:20224043

Qualitative and quantitative analysis of seven oligosaccharides in Morinda officinalis using double-development HPTLC and scanning densitometry.

PubMed

Zhou, Bin; Chang, Jun; Wang, Ping; Li, Jie; Cheng, Dan; Zheng, Peng-Wu

2014-01-01

The quality of Morindaofficinalis, which has been used as a Yang-tonic agent for a long time in China, can be evaluated. A double-development high performance thin layer chromatography (HPTLC) method has been established to simultaneously analyze quality and quantity of seven inulin-type oligosaccharides (DP=3-9) in Morindaofficinalis. The chromatography was performed on a silica gel 60 plate with the 7:5:2:1 proportion (v/v) of n-butanol-isopropanol-water-acetic acid for the first and second developments, respectively. The bands were visualized by the reaction with aniline-diphenylamine-phosphoric acid solution and analyzed by densitometric TLC at 540 nm. Quantification of seven oligosaccharides was achieved by densitometry at 540 nm. The investigated standard sugar had good linearity (R2>0.99) within test ranges. The amounts of seven oligosaccharides were calculated by the relative correction factor (RCF). Therefore, the developed TLC method could be used for quality control of Morindaofficinalis.

Particle size distributions of currently used pesticides in ambient air of an agricultural Mediterranean area

NASA Astrophysics Data System (ADS)

Coscollà, Clara; Muñoz, Amalia; Borrás, Esther; Vera, Teresa; Ródenas, Milagros; Yusà, Vicent

2014-10-01

This work presents first data on the particle size distribution of 16 pesticides currently used in Mediterranean agriculture in the atmosphere. Particulate matter air samples were collected using a cascade impactor distributed into four size fractions in a rural site of Valencia Region, during July to September in 2012 and from May to July in 2013. A total of 16 pesticides were detected, including six fungicides, seven insecticides and three herbicides. The total concentrations in the particulate phase (TSP: Total Suspended Particulate) ranged from 3.5 to 383.1 pg m-3. Most of the pesticides (such as carbendazim, tebuconazole, chlorpyrifos-ethyl and chlorpyrifos-methyl) were accumulated in the ultrafine-fine (<1 μm) and coarse (2.5-10 μm) particle size fractions. Others like omethoate, dimethoate and malathion were presented only in the ultrafine-fine size fraction (<1 μm). Finally, diuron, diphenylamine and terbuthylazine-desethyl-2-OH also show a bimodal distribution but mainly in the coarse size fractions.