Abstract:
PURPOSE:To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. METHODS:We have developed a new approach to the sequence analysis of proteins with multiple transmembrane domains (TMDs) which takes into account the repeated TMD-loop topology. In addition to conventional analyses of the entire sequence, each TMD and its adjacent loop residues (= TMD segments) were analyzed separately as independent structural units. In combination with hydropathy analysis, this approach reveals any changes in the order of the TMD segments in the primary structure and permits TMD alignments among divergent structures even if rearrangements of the order of TMD segments have occurred in the course of evolution. RESULTS:Alignments of TMD segments indicate that the TMD order in PTR transporters may have changed in the process of evolution. Consideration of such changes permits the alignment of homologous TMD segments from PTR transporters belonging to distant akaryotic and eukaryotic phyla. Multiple alignments of TMDs reveal several highly conserved regions that may play a role in transporter function. In comparing the PTR transporters with other transporter gene families, alignment scores using the entire primary structure are too low to support a finding of probable homology. However, statistically significant alignments were observed among individual TMD segments if one disregards the order in which they occur in the primary structure. CONCLUSIONS:Our results support the hypothesis that the PTR transporters may have evolved by rearrangement, duplication, or insertions and deletions of TMD segments as independent modules. This modular structure suggests new alignment strategies for determining functional domains and testing relationship among distant transporter families.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Graul RC,Sadée Wdoi
10.1023/a:1012070726480subject
Has Abstractpub_date
1997-04-01 00:00:00pages
388-400issue
4eissn
0724-8741issn
1573-904Xjournal_volume
14pub_type
杂志文章abstract:PURPOSE:To apply physiologically-based pharmacokinetic (PBPK) modeling to investigate the consequences of reduction in activity of hepatic and intestinal uptake and efflux transporters by cyclosporine and its metabolite AM1. METHODS:Inhibitory potencies of cyclosporine and AM1 against OATP1B1, OATP1B3 and OATP2B1 were...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0918-y
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:To compare the permeation characteristics of amide bond-containing HIV-1 protease inhibitors and their pyrrolinone-containing counterparts across Caco-2 cell monolayers, a model of the intestinal mucosa. METHODS:Transepithelial transport and cellular uptake of three pairs of amide bond-containing and pyrrolino...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011966918959
更新日期:1998-05-01 00:00:00
abstract:PURPOSE:The United States Pharmacopoeia (USP) imposes strict requirements on the geometry and operating conditions of the USP Dissolution Testing Apparatus II. A previously validated Computational Fluid Dynamics (CFD) approach was used here to study the hydrodynamics of USP Apparatus II when the impeller was placed at ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9477-z
更新日期:2008-02-01 00:00:00
abstract::The partitioning of a series of nine nitroimidazole drugs in liposomes (log Km) of various compositions has been determined and compared to their partitioning in the n-octanol/saline system (log K) at 30 degrees C. The log Km ranged from 1.5 to 0.5 and was three- to fourfold greater than the log K; further, the linear...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015931431817
更新日期:1989-05-01 00:00:00
abstract:PURPOSE:Monoamine oxidases (MAOs) are non-CYP enzymes that contribute to systemic elimination of therapeutic agents, and localized on mitochondrial membranes. The aim of the present study was to validate quantitative estimation of metabolic clearance of MAO substrate drugs using human liver microsomes (HLMs). METHODS:...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2140-4
更新日期:2017-06-01 00:00:00
abstract::A rapid quantitative, enantioselective HPLC method for the analysis of the four stereoisomers, (+) and (-) erythro and (+) and (-) threo forms, of mefloquine has been developed using a Chiralpak Ad analytical column containing amylose tris-3,5-dimethylphenyl carbonate coated on silica gel and hexane/ethanol/diethylami...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015832912774
更新日期:1992-12-01 00:00:00
abstract::The electrochemical properties of human cadaver skin were studied in a diffusion cell with impedance spectroscopy as a function of time in the absence and presence of penetration enhancers dodecyl N,N-dimethylamino acetate and Azone. An improved electrochemical model of skin is presented, and combining the novel model...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018984121415
更新日期:1993-03-01 00:00:00
abstract:PURPOSE:A theoretical study was performed to generate a pharmacophore model for chemically diverse structures that specifically interact with the diltiazem binding site of L-type calcium channels. METHODS:Via molecular mechanics and quantum chemical methods solvation energies, logP values, conformational and electroni...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015037800903
更新日期:1999-10-01 00:00:00
abstract:PURPOSE:In pharmacokinetic (PK)/pharmacodynamic (PD) modelling and simulations (M&S), omitting dropouts can cause inaccuracies in parameter estimation and clinical trial simulations (CTS). This study examines the impact of different imputation methods for missing data on the interpretation of model results, as well as ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1380-9
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:To determine the correlation among progesterone dose, rate of import of progesterone-occupied progesterone receptor (PR) complexes into the nucleus of cells, and transcriptional activity of progesterone-PR complexes. METHODS:Live cell imaging and time-lapse microscopy of green fluorescent protein-tagged PR wer...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1026127015761
更新日期:2003-10-01 00:00:00
abstract:PURPOSE:Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-8815-2
更新日期:2006-01-01 00:00:00
abstract::Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led t...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-008-9634-z
更新日期:2008-12-01 00:00:00
abstract:PURPOSE:To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS:TNF-α inhibitors in their o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2341-x
更新日期:2018-02-05 00:00:00
abstract:PURPOSE:To investigate the effect of benzofusion on NO donor properties and related biological activities of the furoxan system. The biological properties considered were the ability to increase the cytosolic levels of cGMP in C6 cells and vasodilation. METHODS:NO donor properties were investigated either in the prese...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018974409622
更新日期:1999-06-01 00:00:00
abstract:PURPOSE:The objective of the present work was to prepare safe and effective Ciclosporin A Lipid nanocapsule (CsA-LNC) eye-drops for the treatment of DED. METHODS:The phase-inversion method was used to prepared different sizes CsA-LNC. CsA biodistribution in ocular after topical administration in rabbits was analyzed b...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02872-2
更新日期:2020-07-14 00:00:00
abstract::Pharmacokinetic/pharmacodynamic (PK/PD)-modeling links dose-concentration relationships (PK) and concentration-effect relationships (PD), thereby facilitating the description and prediction of the time course of drug effects resulting from a certain dosing regimen. PK/PD-modeling approaches can basically be distinguis...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011907920641
更新日期:1999-02-01 00:00:00
abstract:PURPOSE:The objective of this investigation is to develop a rational design of Osteotropic Drug Delivery System (ODDS), which we have proposed as a novel method for drug delivery to the skeleton via bisphosphonic prodrug, based on the relationship between physicochemical and pharmacokinetic properties of bisphosphonate...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011033326980
更新日期:2001-05-01 00:00:00
abstract:PURPOSE:To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. METHODS:Mannitol a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0743-3
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective "filtering" effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and su...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016205520044
更新日期:1995-11-01 00:00:00
abstract:PURPOSE:Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in mo...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-2027-9
更新日期:2016-12-01 00:00:00
abstract::Loracarbef is an oral 1-carba-1-dethiacephalosporin antibiotic structurally related to cefaclor. Like many beta-lactam antibiotics, loracarbef exists in several hydrated crystalline forms. The pH-solubility profile curve for loracarbef monohydrate is U-shaped, resembling those of other zwitterionic cephalosporins. Lor...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018949709797
更新日期:1992-02-01 00:00:00
abstract:PURPOSE:The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS:The impact of sodium taurodeoxycholate (STDC), sodium dodec...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2332-y
更新日期:2018-02-21 00:00:00
abstract:PURPOSE:The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. METHOD:Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1335-1
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. METHODS:25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1667-5
更新日期:2015-09-01 00:00:00
abstract:PURPOSE:The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. MATERIALS AND METHODS...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1593-y
更新日期:2015-06-01 00:00:00
abstract::Porcine pancreatic elastase, a well-characterized serine protease, has been used as a model to assess the effects of excessive humidity on solid-state stability of the lyophilized protein. Elastase lyophilized without excipients retained full activity immediately after freeze-drying but became denatured upon continued...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018979410338
更新日期:1993-10-01 00:00:00
abstract:PURPOSE:Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and we proposed that the cytotoxicity is through apoptosis. In this study, we examined the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1024441702398
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:Oral bioavailability for antisense oligonucleotides has recently been reported but the mechanistic details are not known. The proposed oral delivery of nucleic acids will, therefore, require an understanding of the membrane binding interactions, cell uptake and transport of oligonucleotides across the human gas...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016002606705
更新日期:1996-07-01 00:00:00
abstract:PURPOSE:Generalizations based upon behavior of small molecules have established that a crystalline solid is generally much more stable toward chemical degradation than is the amorphous solid. This study examines the validity of this generalization for proteins using biosynthetic human insulin as the model protein. MET...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012164520429
更新日期:1997-10-01 00:00:00
abstract:PURPOSE:The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS:Mathematical modeling, applied to transdermal d...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016216611809
更新日期:1995-12-01 00:00:00