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排序方式: 共有244条查询结果,搜索用时 31 毫秒
31.
Romberg B Oussoren C Snel CJ Carstens MG Hennink WE Storm G 《Biochimica et biophysica acta》2007,1768(3):737-743
'Stealth' liposomes with a poly(ethylene glycol) (PEG) coating are frequently studied for drug delivery and diagnostic purposes because of their prolonged blood circulation kinetics. However, several recent reports have demonstrated that PEG-liposomes are rapidly cleared at single low lipid doses (<1 micromol/kg) and upon repeated administration (time interval between the injections 5 days-4 weeks). Recently, poly(amino acid)-based stealth liposome coatings have been developed as alternative to the PEG-coating. In this study, the pharmacokinetic behavior of liposomes coated with the poly(amino acid) poly(hydroxyethyl-l-asparagine) (PHEA) was evaluated at low lipid doses and upon repeated administration in rats. Blood circulation times and hepatosplenic localization of PHEA-liposomes were assessed after intravenous injection. When administered at a dose of 0.25 micromol/kg or less, PHEA-liposomes showed significantly longer blood circulation times than PEG-liposomes. A second dose of PHEA-liposomes 1 week after the first injection was less rapidly cleared from the circulation than a second dose of PEG-liposomes. Although the mechanisms behind these observations are still not clear yet, the use of PHEA-liposomes appears beneficial when single low lipid doses and/or repeated dosing schedules are being applied. 相似文献
32.
Terence A. Ketter Mark A. Frye Gabriela Corá-Locatelli Timothy A. Kimbrell Robert M. Post 《Cellular and molecular neurobiology》1999,19(4):511-532
1. The mood stabilizers lithium, carbamazepine (CBZ), and valproate (VPA), have differing pharmacokinetics, structures, mechanisms of action, efficacy spectra, and adverse effects. Lithium has a low therapeutic index and is renally excreted and hence has renally-mediated but not hepatically-mediated drug–drug interactions.2. CBZ has multiple problematic drug–drug interactions due to its low therapeutic index, metabolism primarily by a single isoform (CYP3A3/4), active epoxide metabolite, susceptibility to CYP3A3/4 or epoxide hydrolase inhibitors, and ability to induce drug metabolism (via both cytochrome P450 oxidation and conjugation). In contrast, VPA has less prominent neurotoxicity and three principal metabolic pathways, rendering it less susceptible to toxicity due to inhibition of its metabolism. However, VPA can increase plasma concentrations of some drugs by inhibiting metabolism and increase free fractions of certain medications by displacing them from plasma proteins.3. Older anticonvulsants such as phenobarbital and phenytoin induce hepatic metabolism, may produce toxicity due to inhibition of their metabolism, and have not gained general acceptance in the treatment of primary psychiatric disorders.4. The newer anticonvulsants felbamate, lamotrigine, topiramate, and tiagabine have different hepatically-mediated drug–drug interactions, while the renally excreted gabapentin lacks hepatic drug–drug interactions but may have reduced bioavailability at higher doses.5. Investigational anticonvulsants such as oxcarbazepine, vigabatrin, and zonisamide appear to have improved pharmacokinetic profiles compared to older agents.6. Thus, several of the newer anticonvulsants lack the problematic drug-drug interactions seen with older agents, and some may even (based on their mechanisms of action and preliminary preclinical and clinical data) ultimately prove to have novel psychotropic effects. 相似文献
33.
Cor D. Schoen Conchita C.G.M. Schulkes Jos C. Arents Roel van Driel 《Journal of cellular biochemistry》1996,60(3):411-423
Dictyostelium discoideum cells respond to chemoattractants by transient activation of guanylate cyclase. Cyclic GMP is a second messenger that transduces the chemotactic signal. We used an electropermeabilized cell system to investigate the regulation of guanylate cyclase. Enzyme activity in permeabilized cells was dependent on the presence of a nonhydrolysable GTP analogue (e.g., GTPγS), which could not be replaced by GTP, GDP, or GMP. After the initiation of the guanylate cyclase reaction in permeabilized cells only a short burst of activity is observed, because the enzyme is inactivated with a t1.2 of about 15 s. We show that inactivation is not due to lack of substrate, resealing of the pores in the cell membrane, product inhibition by cGMP, or intrinsic instability of the enzyme. Physiological concentrations of Ca2+ ions inhibited the enzyme (half-maximal effect at 0.3 μM), whereas InsP3 had no effect. Once inactivated, the enzyme could only be reactivated after homogenization of the permeabilized cells and removal of the soluble cell fraction. This suggests that a soluble factor is involved in an autonomous process that inactivates guanylate cyclase and is triggered only after the enzyme is activated. The initial rate of guanylate cyclase activity in permeabilized cells is similar to that in intact, chemotactically activated cells. Moreover, the rate of inactivation of the enzyme in permeabilized cells and that due to adaptation in vivo are about equal. This suggests that the activation and inactivation of guanylate cyclase observed in this permeabilized cell system is related to that of chemotactic activation and adaptation in intact cells. © 1996 Wiley-Liss, Inc. 相似文献
34.
The spider tree of life: phylogeny of Araneae based on target‐gene analyses from an extensive taxon sampling
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Ward C. Wheeler Jonathan A. Coddington Louise M. Crowley Dimitar Dimitrov Pablo A. Goloboff Charles E. Griswold Gustavo Hormiga Lorenzo Prendini Martín J. Ramírez Petra Sierwald Lina Almeida‐Silva Fernando Alvarez‐Padilla Miquel A. Arnedo Ligia R. Benavides Silva Suresh P. Benjamin Jason E. Bond Cristian J. Grismado Emile Hasan Marshal Hedin Matías A. Izquierdo Facundo M. Labarque Joel Ledford Lara Lopardo Wayne P. Maddison Jeremy A. Miller Luis N. Piacentini Norman I. Platnick Daniele Polotow Diana Silva‐Dávila Nikolaj Scharff Tamás Szűts Darrell Ubick Cor J. Vink Hannah M. Wood Junxia Zhang 《Cladistics : the international journal of the Willi Hennig Society》2017,33(6):574-616
35.
Nucleotide sequence data were generated from the gene regions COI, 16S, and arginine kinase to assess genetic variation within the Palearctic parasitoid, Microctonus aethiopoides, reared from Sitona discoideus, S. hispidulus, and Hypera postica collected from two proximate locations in Mediterranean France. Partitioned Bayesian phylogenetic analyses of the molecular data provided strong support for the presence of at least two M. aethiopoides biotypes, one associated with Hypera species and the other with Sitona species. These new results combined with previously published data from 14 countries show that M. aethiopoides genetic variation is much more strongly correlated with host taxon than with sampling location. This contrasts with earlier perceptions that M. aethiopoides exhibits significant geographic variation, and helps to explain the widely varying biological control outcomes that have been obtained following the introductions of M. aethiopoides to Australia, New Zealand, and North America. The results strongly suggest that success rates and environmental safety in biological control would both be improved by ensuring that parasitoids collected in the native range are reared from the same host species as the one being targeted for control in the region of introduction. The results also provided insights both on the evolution of M. aethiopoides' host range, and on its evolutionary transition between solitary and gregarious larval development. 相似文献
36.
The relation between central metabolism and the penicillin biosynthesis pathway in Penicillium chrysogenum was studied by manipulating the steady-state flux in both pathways. A high producing industrial strain was cultivated at a growth rate mu=0.05 h(-1) in glucose-limited chemostat cultures, both under penicillin-G producing and non-producing conditions. Non-producing conditions were accomplished in two ways: (1) by cultivation without addition of the side chain precursor phenylacetic acid and (2) by cultivation of a mutant strain which lost all copies of the gene cluster coding for the penicillin biosynthesis pathway. Manipulation of the fluxes through central metabolism was obtained by cultivation on either glucose or ethanol as sole carbon source. A positive relation was observed between metabolite concentrations and carbon flux in central metabolism. Furthermore, in many cases a positive relation was found between the concentrations of free amino acids and their direct precursors in central metabolism. This corresponds with control of the biosynthesis of these amino acids via feed back inhibition by the end product. With respect to the penicillin production pathway, the flux seems not influenced by two of the three precursor amino acids, namely alphaAAA and valine but is only influenced by cysteine, which requires a large NADPH supply, and the ATP level. An interesting observation is that the absence of penicillin production seems to stimulate storage metabolism (trehalose metabolism). This leads to the final conclusion that the penicillin production flux appears to be mostly influenced by the availability of energy and redox cofactors, where ATP is supposed to exert its influence at ACV-synthetase and NADPH at the cysteine level. 相似文献
37.
Takwa M Xiao Y Simpson N Malmström E Hult K Koning CE Heise A Martinelle M 《Biomacromolecules》2008,9(2):704-710
2-Hydroxyethyl methacrylate (HEMA) was used as initiator for the enzymatic ring-opening polymerization (ROP) of omega-pentadecalactone (PDL) and epsilon-caprolactone (CL). The lipase B from Candida antarctica was found to catalyze the cleavage of the ester bond in the HEMA end group of the formed polyesters, resulting in two major transesterification processes, methacrylate transfer and polyester transfer. This resulted in a number of different polyester methacrylate structures, such as polymers without, with one, and with two methacrylate end groups. Furthermore, the 1,2-ethanediol moiety (from HEMA) was found in the polyester products as an integral part of HEMA, as an end group (with one hydroxyl group) and incorporated within the polyester (polyester chains acylated on both hydroxyl groups). After 72 h, as a result of the methacrylate transfer, 79% (48%) of the initial amount of the methacrylate moiety (from HEMA) was situated (acylated) on the end hydroxyl group of the PPDL (PCL) polyester. In order to prepare materials for polymer networks, fully dimethacrylated polymers were synthesized in a one-pot procedure by combining HEMA-initiated ROP with end-capping using vinyl methacrylate. The novel PPDL dimethacrylate (>95% incorporated methacrylate end groups) is currently in use for polymer network formation. Our results show that initiators with cleavable ester groups are of limited use to obtain well-defined monomethacrylated macromonomers due to the enzyme-based transesterification processes. On the other hand, when combined with end-capping, well-defined dimethacrylated polymers (PPDL, PCL) were prepared. 相似文献
38.
Datasets from the mitochondrial gene regions NADH dehydrogenase subunit I (ND1) and cytochrome c oxidase subunit I (COI) of the 20 species in the New Zealand wolf spider (Lycosidae) genus Anoteropsis were generated. Sequence data were phylogenetically analysed using parsimony and maximum likelihood analyses. The phylogenies generated from the ND1 and COI sequence data and a previously generated morphological dataset were significantly congruent (p<0.001). Sequence data were combined with morphological data and phylogenetically analysed using parsimony. The ND1 region sequenced included part of tRNALeu(CUN), which appears to have an unstable amino-acyl arm and no TψC arm in lycosids. Analyses supported the existence of five species groups within Anoteropsis and the monophyly of species represented by multiple samples. A radiation of Anoteropsis species within the last five million years is inferred from the ND1 and COI likelihood phylograms, habitat and geological data, which also indicates that Anoteropsis arrived in New Zealand some time after it separated from Gondwana. 相似文献
39.
Federico Fogolari Haritha Haridas Alessandra Corazza Paolo Viglino Davide Corà Michele Caselle Gennaro Esposito Luigi E Xodo 《BMC structural biology》2009,9(1):64-20
Background
Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G3X n1G3X n2G3X n3G3 motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of G-quadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data. 相似文献40.
Daniela Camargos Costa Ana Paula Madureira Lara Cotta Amaral Bruno Ant?nio Marinho Sanchez Luciano Teixeira Gomes Cor Jésus Fernandes Fontes Jean Ezequiel Limongi Cristiana Ferreira Alves de Brito Luzia Helena Carvalho 《Memórias do Instituto Oswaldo Cruz》2014,109(1):21-28
The polymerase chain reaction (PCR)-based methods for the diagnosis of malaria
infection are expected to accurately identify submicroscopic parasite carriers.
Although a significant number of PCR protocols have been described, few studies have
addressed the performance of PCR amplification in cases of field samples with
submicroscopic malaria infection. Here, the reproducibility of two well-established
PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18
small subunit rRNA gene) were evaluated in a panel of 34 blood field samples from
individuals that are potential reservoirs of malaria infection, but were negative for
malaria by optical microscopy. Regardless of the PCR protocol, a large variation
between the PCR replicates was observed, leading to alternating positive and negative
results in 38% (13 out of 34) of the samples. These findings were quite different
from those obtained from the microscopy-positive patients or the unexposed
individuals; the diagnosis of these individuals could be confirmed based on the high
reproducibility and specificity of the PCR-based protocols. The limitation of PCR
amplification was restricted to the field samples with very low levels of
parasitaemia because titrations of the DNA templates were able to detect < 3
parasites/µL in the blood. In conclusion, conventional PCR protocols require careful
interpretation in cases of submicroscopic malaria infection, as inconsistent and
false-negative results can occur. 相似文献