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991.
David S Phelps Todd M Umstead Omar A Quintero Christopher M Yengo Joanna Floros 《Proteome science》2011,9(1):67
Background
Mice lacking surfactant protein-A (SP-A-/-; knockout; KO) exhibit increased vulnerability to infection and injury. Although many bronchoalveolar lavage (BAL) protein differences between KO and wild-type (WT) are rapidly reversed in KO after infection, their clinical course is still compromised. We studied the impact of SP-A on the alveolar macrophage (AM) proteome under basal conditions. Male SP-A KO mice were SP-A-treated (5 micrograms/mouse) and sacrificed in 6 or 18 hr. The AM proteomes of KO, SP-A-treated KO, and WT mice were studied by 2D-DIGE coupled with MALDI-ToF/ToF and AM actin distribution was examined by phalloidon staining.Results
We observed: a) significant differences from KO in WT or exogenous SP-A-treated in 45 of 76 identified proteins (both increases and decreases). These included actin-related/cytoskeletal proteins (involved in motility, phagocytosis, endocytosis), proteins of intracellular signaling, cell differentiation/regulation, regulation of inflammation, protease/chaperone function, and proteins related to Nrf2-mediated oxidative stress response pathway; b) SP-A-induced changes causing the AM proteome of the KO to resemble that of WT; and c) that SP-A treatment altered cell size and F-actin distribution.Conclusions
These differences are likely to enhance AM function. The observations show for the first time that acute in vivo SP-A treatment of KO mice, under basal or unstimulated conditions, affects the expression of multiple AM proteins, alters F-actin distribution, and can restore much of the WT phenotype. We postulate that the SP-A-mediated expression profile of the AM places it in a state of "readiness" to successfully conduct its innate immune functions and ensure lung health.992.
993.
Cortés-Espinosa DV Absalón ÁE Sanchez N Loera O Rodríguez-Vázquez R Fernández FJ 《Journal of molecular microbiology and biotechnology》2011,21(3-4):120-129
A strain of Aspergillus niger, previously isolated from sugarcane bagasse because of its capacity to degrade phenanthrene in soil by solid culture, was used to express a manganese peroxidase gene (mnp1) from Phanerochaete chrysosporium, aiming at increasing its polycyclic aromatic hydrocarbons degradation capacity. Transformants were selected based on their resistance to hygromycin B and the discoloration induced on Poly R-478 dye by the peroxidase activity. The recombinant A. niger SBC2-T3 strain developed MnP activity and was able to remove 95% of the initial phenanthrene (400 ppm) from a microcosm soil system after 17 days, whereas the wild strain removed 72% under the same conditions. Transformation success was confirmed by PCR amplification using gene-specific primers, and a single fragment (1,348 bp long, as expected) of the recombinant mnp1 was amplified in the DNA from transformants, which was absent from the parental strain. 相似文献
994.
995.
Automated powder dispensing systems enable supplying early clinical studies using drug-in-capsule approach, which is material
sparing and requires a minimum amount of resources. However, the inability of accurately filling the capsule with a small
amount, e.g., several micrograms, of drug limits the use of these systems for potent drugs. We demonstrate that formulated
powder blends can be used to successfully fill capsules containing 5 μg to 5 mg of drug with adequate content uniformity.
Effective formulation and process strategies that enable this approach are presented with examples. 相似文献
996.
González-Díaz H Prado-Prado F García-Mera X Alonso N Abeijón P Caamaño O Yáñez M Munteanu CR Pazos A Dea-Ayuela MA Gómez-Muñoz MT Garijo MM Sansano J Ubeira FM 《Journal of proteome research》2011,10(4):1698-1718
Many drugs with very different affinity to a large number of receptors are described. Thus, in this work, we selected drug-target pairs (DTPs/nDTPs) of drugs with high affinity/nonaffinity for different targets. Quantitative structure-activity relationship (QSAR) models become a very useful tool in this context because they substantially reduce time and resource-consuming experiments. Unfortunately, most QSAR models predict activity against only one protein target and/or they have not been implemented on a public Web server yet, freely available online to the scientific community. To solve this problem, we developed a multitarget QSAR (mt-QSAR) classifier combining the MARCH-INSIDE software for the calculation of the structural parameters of drug and target with the linear discriminant analysis (LDA) method in order to seek the best model. The accuracy of the best LDA model was 94.4% (3,859/4,086 cases) for training and 94.9% (1,909/2,012 cases) for the external validation series. In addition, we implemented the model into the Web portal Bio-AIMS as an online server entitled MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (MIND-BEST), located at http://miaja.tic.udc.es/Bio-AIMS/MIND-BEST.php . This online tool is based on PHP/HTML/Python and MARCH-INSIDE routines. Finally, we illustrated two practical uses of this server with two different experiments. In experiment 1, we report for the first time a MIND-BEST prediction, synthesis, characterization, and MAO-A and MAO-B pharmacological assay of eight rasagiline derivatives, promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF and -TOF/TOF MS, MASCOT search, 3D structure modeling with LOMETS, and MIND-BEST prediction for different peptides as new protein of the found in the proteome of the bird parasite Trichomonas gallinae, which is promising for antiparasite drug targets discovery. 相似文献
997.
Guedes FL de Oliveira BG Hernandes MZ De Simone CA Veiga FJ de Lima Mdo C Pitta IR Galdino SL Neto PJ 《AAPS PharmSciTech》2011,12(1):401-410
Solid dispersions have been used as a strategy to improve the solubility, dissolution rate, and bioavailability of poor water-soluble
drugs. The increase of the dissolution rate presented by (5Z)-3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (LPSF/FZ4) from the solid dispersions is related to
the existence of intermolecular interactions of hydrogen bond type (>N–H...O<) between the amide group (>N–H) of the LPSF/FZ4 and the ether group (–O–) of the polyethyleneglycol polymer, or the carbonyl
(C=O) of the polyvinylpyrrolidone polymer (PVP). The intensity of these interactions is directly reflected in the morphology
acquired by LPSF/FZ4 in these systems, where a new solid phase, in the form of amorphous aggregates of irregular size, was
identified through scanning electron microscopy and confirmed in the characterizations achieved using X-ray diffraction and
thermal analysis of DSC. The solid dispersions with the polymer PVP, in higher concentrations, were revealed to be the best
option to be used in the formulations of LPSF/FZ4 in both theoretical and experimental studies. 相似文献
998.
Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation,
where poorly soluble acidic AMG 009 molecule was intimately mixed and compressed together with a basic pH modifier (e.g., sodium carbonate) and nucleation inhibitor hydroxypropyl methylcellulose K100 LV (HPMC K100 LV), was demonstrated previously. However, not all acidic or basic drugs are compatible with basic or acidic pH
modifiers either chemically or physically. The objective of this study is to investigate whether similar dissolution enhancement
of AMG 009 can be achieved from a bilayer dosage form, where AMG 009 and sodium carbonate are placed in a separate layer with
or without the addition of HPMC K100 LV in each layer. Study results indicate that HPMC K100 LV-containing bilayer dosage
forms gained similar dissolution enhancement as matrix dosage forms did. Bilayer dosage forms without HPMC K100 LV benefitted
the least from dissolution enhancement. 相似文献
999.
1000.