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991.
Felix Schneider Melanie Hoppe Mirko Koziolek Werner Weitschies 《AAPS PharmSciTech》2018,19(7):2843-2850
Despite extensive research in the field of gastroretentive dosage forms, this “holy grail” of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions. 相似文献
992.
Wei-Zhong Zhao Hsiang-Tsui Wang Hui-Ju Huang Yu-Li Lo Anya Maan-Yuh Lin 《Molecular neurobiology》2018,55(1):130-137
Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson’s disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation. Furthermore, baicalein reduced acrolein-induced elevations in glial fibrillary acidic protein (a biomarker of activated astrocytes), ED-1 (a biomarker of activated microglia), and mature cathepsin B levels (a cysteine lysosomal protease), suggesting that baicalein attenuated acrolein-induced neuroinflammation. Moreover, baicalein attenuated acrolein-induced caspase 1 activation (a pro-inflammatory caspase) and interleukin-1β levels, indicating that baicalein prevented acrolein-induced inflammasome activation. In addition, baicalein significantly attenuated acrolein-induced caspase 3 activation (a biomarker of apoptosis) as well as acrolein-induced elevation in receptor interacting protein kinase (RIPK) 3 levels (an initiator of necroptosis), indicating that baicalein attenuated apoptosis and necroptosis. At the same time, baicalein mitigated acrolein-induced reduction in dopamine levels in the striatum ipsilateral to acrolein-infused SN. In conclusion, our data suggest that baicalein is neuroprotective via inhibiting oxidative stress, protein conjugation, and inflammation. Furthermore, baicalein prevents acrolein-induced program cell deaths, suggesting that baicalein is therapeutically useful for slowing PD progression. 相似文献
993.
Inês Carqueijeiro Thomas Dugé de Bernonville Arnaud Lanoue Thu‐Thuy Dang Christiana N Teijaro Christian Paetz Kevin Billet Angela Mosquera Audrey Oudin Sébastien Besseau Nicolas Papon Gaëlle Glévarec Lucía Atehortùa Marc Clastre Nathalie Giglioli‐Guivarc'h Bernd Schneider Benoit St‐Pierre Rodrigo B. Andrade Sarah E. O'Connor Vincent Courdavault 《The Plant journal : for cell and molecular biology》2018,94(3):469-484
994.
Synthesis of novel mono and bis nitric oxide donors with high cytocompatibility and release activity
Tanya Sahyoun Caroline Gaucher Yi Zhou Naïm Ouaini Raphaël Schneider Axelle Arrault 《Bioorganic & medicinal chemistry letters》2018,28(20):3329-3332
Four compounds bearing amidoxime functions were synthetized: (1) 2a,b bearing an aromatic amidoxime function, (2) 2c bearing an aliphatic amidoxime function, and (3) 2d bearing aromatic and aliphatic amidoximes functions. The ability of these compounds to release NO was evaluated in vitro using the oxidative metabolism of cytochrome P450 from rat liver microsomes. Results obtained demonstrate that all amidoximes were able to release NO with a highest amount of NO produced by the 2a aromatic amidoxime. Moreover, all amidoximes exhibit cytocompatibility with human aorta smooth muscle cells. Using intracellular S-nitrosothiol formation as a marker of NO bioavailability, compounds 2a–c were demonstrated to deliver a higher amount of NO in the intracellular environment than the reference. Considering that the concentration of the bis-amidoxime 2d was two times lower that than of 2a and 2b, we can assume that 2d is the most potent molecule among the tested compounds for NO release. 相似文献
995.
David Castonguay Julien Dufort-Gervais Caroline Ménard Manavi Chatterjee Rémi Quirion Bruno Bontempi Jay S. Schneider Amy F.T. Arnsten Angus C. Nairn Christopher M. Norris Guylaine Ferland Erwan Bézard Pierrette Gaudreau Paul J. Lombroso Jonathan Brouillette 《Current biology : CB》2018,28(7):1079-1089.e4
996.
Samuel J Atkinson Aleksander M Gontarczyk Abdullah AA Alghamdi Tim S Ellison Robert T Johnson Wesley J Fowler Benjamin M Kirkup Bernardo C Silva Bronwen E Harry Jochen G Schneider Katherine N Weilbaecher Mette M Mogensen Mark D Bass Maddy Parsons Dylan R Edwards Stephen D Robinson 《EMBO reports》2018,19(7)
Integrin β3 is seen as a key anti‐angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro‐ or anti‐angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3‐dependent adhesome. We show that depletion of β3‐integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3‐integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2‐driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced. 相似文献
997.
Ian F. Miller India Schneider‐Crease Charles L. Nunn Michael P. Muehlenbein 《Ecology and evolution》2018,8(13):6738-6747
Accurately estimating infection prevalence is fundamental to the study of population health, disease dynamics, and infection risk factors. Prevalence is estimated as the proportion of infected individuals (“individual‐based estimation”), but is also estimated as the proportion of samples in which evidence of infection is detected (“anonymous estimation”). The latter method is often used when researchers lack information on individual host identity, which can occur during noninvasive sampling of wild populations or when the individual that produced a fecal sample is unknown. The goal of this study was to investigate biases in individual‐based versus anonymous prevalence estimation theoretically and to test whether mathematically derived predictions are evident in a comparative dataset of gastrointestinal helminth infections in nonhuman primates. Using a mathematical model, we predict that anonymous estimates of prevalence will be lower than individual‐based estimates when (a) samples from infected individuals do not always contain evidence of infection and/or (b) when false negatives occur. The mathematical model further predicts that no difference in bias should exist between anonymous estimation and individual‐based estimation when one sample is collected from each individual. Using data on helminth parasites of primates, we find that anonymous estimates of prevalence are significantly and substantially (12.17%) lower than individual‐based estimates of prevalence. We also observed that individual‐based estimates of prevalence from studies employing single sampling are on average 6.4% higher than anonymous estimates, suggesting a bias toward sampling infected individuals. We recommend that researchers use individual‐based study designs with repeated sampling of individuals to obtain the most accurate estimate of infection prevalence. Moreover, to ensure accurate interpretation of their results and to allow for prevalence estimates to be compared among studies, it is essential that authors explicitly describe their sampling designs and prevalence calculations in publications. 相似文献
998.
HSSP is a derived database merging structural (3-D) and sequence (1-D) information. For each protein of known 3-D structure from the Protein Data Bank (PDB), the database has a multiple sequence alignment of all available homologues and a sequence profile characteristic of the family. The list of homologues is the result of a database search in SwissProt using a position-weighted dynamic programming method for sequence profile alignment (MaxHom). The database is updated frequently. The listed homologues are very likely to have the same 3-D structure as the PDB protein to which they have been aligned. As a result, the database is not only a database of aligned sequence families, but also a database of implied secondary and tertiary structures covering 29% of all SwissProt-stored sequences. 相似文献
999.
Identification, Localization, and Expression of Two Novel Human Genes Similar to Deoxyribonuclease I
Anna M. Rodriguez David Rodin Hideki Nomura Cynthia C. Morton Stanislawa Weremowicz Michael C. Schneider 《Genomics》1997,42(3):507
Two novel cDNAs, DNAS1L2 and DNAS1L3, are predicted to encode proteins of 299 and 305 amino acids with 56 and 46% residue identity (71 and 63% similarity), respectively, to deoxyribonuclease I (DNase I). DNAS1L2 is located on a 16p13.3 cosmid, while DNAS1L3 maps to 3p14.3–p21.1 by fluorescencein situhybridization and by PCR analysis of a radiation hybrid panel. Northern analysis revealed DNAS1L3 expression nearly exclusively in liver, while DNAS1L2 expression was detected in brain by RT-PCR. The previously defined DNL1L or DNAS1L1 is expressed highest in heart and skeletal muscle, while DNase I is expressed in the pancreas, parotid gland, and kidney. Thus, to date, four DNase I-like genes that show different tissue expression patterns are known. A comparison of DNAS1L1, DNAS1L2, and DNAS1L3 with the well-characterized DNase I suggests that the DNAS1L proteins are unlikely to be glycosylated or bind actin; however, catalytic and calcium- and DNA-binding residues are conserved, and potentially cleavable signal peptides are present among all these proteins. This analysis also identifies regions of high conservation among these proteins with no currently assigned function. 相似文献
1000.
Marmoset phylogenetics, conservation perspectives, and evolution of the mtDNA control region 总被引:3,自引:1,他引:2
Tagliaro CH; Schneider MP; Schneider H; Sampaio IC; Stanhope MJ 《Molecular biology and evolution》1997,14(6):674-684
Marmosets (genus Callithrix) are a diverse group of platyrrhine primates
with 13-15 purported taxa, many of them considered endangered.
Morphological analyses constitute most of the basis for recognition of
these forms as distinct taxa. The purpose of this study was to provide a
molecular view, based on mitochondrial control region sequences, of the
evolutionary history of the marmosets, concomitant with a molecular
phylogenetic perspective on species diversity within the group. An
additional purpose was to provide the first comparative examination of a
complete New World monkey control region sequence with those of other
mammals. The phylogenetic analyses provide convincing support for a split
between the Atlantic forest and Amazonian marmosets, with the inclusion of
the pygmy marmoset (Cebuella pygmaea) at the base of the Amazonian clade.
The earliest branch of the Atlantic forest group was C. aurita. In the
Amazonian group, the analyses do not support the recognition of C.
humeralifer and the recently described C mauesi as distinct taxa. They do,
however, support a clear distinction between C. argentata and a strongly
supported mixed clade of C. humeralifer and C. mauesi. In the Atlantic
forest group, the phylogenetic tree suggests mixing between C. penicillata,
C. kuhli, and possibly C. jacchus. Most of the sequence features
characteristic of other mammal control regions were also evident in
marmosets, with the exception that conserved sequence blocks (CSBs) 2 and 3
were not clearly identifiable. Tandem repeat units often associated with
heteroplasmy in a variety of other mammals were not evident in the marmoset
sequences.
相似文献