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 possible involvement of a mitochondrial-driven pathway in this process. METHODS:Cell death was determined by the WST-1 cell viability test, and changes in apoptotic parameters [i.e., release of mitochondrial cytochrome c, activation of caspases, cleavage of poly(ADP-ribose) polymerase (PARP)] were detected by Western blotting. RESULTS:H4 cells treated with R(+)-MA showed typical signs of mitochondrial apoptosis, i.e., release of mitochondrial cytochrome c into the cytosol and activation of initiator caspase-9. Moreover, activation of the executor caspase-3 was observed following cannabinoid treatment. Cells were fully protected from apoptotic cell death by the caspase-3 inhibitor Ac-DEVD-CHO, indicating a crucial role for caspase-3 activation in R(+)-MA-elicited apoptosis. Furthermore, cleavage of the caspase-3 target protein PARP was registered. All of the aforementioned effects were substantially reduced by the selective COX-2 inhibitor celecoxib (1 muM) at a pharmacologically relevant, nonapoptotic concentration. CONCLUSION:R(+)-MA-induced apoptosis is mediated via a mitochondrial-dependent pathway that becomes activated, at least in part, through up-regulation of the COX-2 enzyme.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Eichele K,Weinzierl U,Ramer R,Brune K,Hinz Bdoi
10.1007/s11095-005-8815-2subject
Has Abstractpub_date
2006-01-01 00:00:00pages
90-4issue
1eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
杂志文章abstract:PURPOSE:The purpose of the present study was to explore the involvement of indoxyl sulfate (IS) in nephrotoxicity and central nervous system (CNS) toxicity in cisplatin (CDDP)-treated rats. MATERIALS AND METHODS:Renal function was evaluated by serum creatinine and BUN levels. The IS levels in the serum, brain and kidn...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9183-2
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin. METHODS:A hydroxyl terminal group of PLGA was activated by p-nitrophenyl chloroformate and reacte...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018908421434
更新日期:1999-07-01 00:00:00
abstract::Magnetic nanoparticles are useful as contrast agents for magnetic resonance imaging (MRI). Paramagnetic contrast agents have been used for a long time, but more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been discovered to influence MRI contrast as well. In contrast to paramagnetic contrast agent...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-012-0711-y
更新日期:2012-05-01 00:00:00
abstract:PURPOSE:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016225707807
更新日期:1995-09-01 00:00:00
abstract::The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016312827680
更新日期:1985-09-01 00:00:00
abstract::Polymeric biomaterials have extensively been used in medicinal applications. However, factors that determine their biocompatibility are still not very clear. This article reviews various effects of the chemical structure and the surface properties of polymeric biomaterials on their biocompatibility, including protein ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1023/b:pham.0000036909.41843.18
更新日期:2004-08-01 00:00:00
abstract::The simultaneous diffusion and metabolism of the D- and L-isomers of the aminopeptidase substrate, leucine-p-nitroanilide (LPNA), were examined in vitro in the hamster cheek pouch. L-LPNA was completely hydrolyzed during diffusion across the cheek pouch, whereas D-LPNA crossed the cheek pouch intact. The metabolic bar...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015949614437
更新日期:1989-11-01 00:00:00
abstract::Alpha- and beta-cyclodextrins and their hydroxypropyl derivatives were converted by the reaction with chlorosulfonic acid in pyridine to the corresponding sulfates. Cyclodextrin sulfates were shown by fast-atom bombardment mass spectrometry (negative ion mode, triethanolamine matrix) to be mixtures with nearly symmetr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015854402122
更新日期:1991-09-01 00:00:00
abstract:PURPOSE:Understanding the critical factors governing the crystallization tendency of organic compounds is vital when assessing the feasibility of an amorphous formulation to improve oral bioavailability. The objective of this study was to investigate potential links between viscosity and crystallization tendency for or...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0540-4
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:The aim of this study is to investigate the effects of 50% ethyl acetate extracts of grapefruit juice (GFJ) and orange juice (OJ) on the transport activity of P-glycoprotein (P-gp) in the rat small intestine. METHODS:The efflux of P-gp substrates from rat everted sac in the absence or presence of verapamil, GF...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016100715125
更新日期:2002-06-01 00:00:00
abstract::The pharmacokinetics of methylergometrine were investigated in the rat, with emphasis on the role of biliary excretion and enterohepatic recirculation in the overall disposition of the drug. A linked-rat model, where the bile from a rat receiving a constant rate of iv infusion of methylergometrine was allowed to flow ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015871122537
更新日期:1990-01-01 00:00:00
abstract::This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015841715384
更新日期:1991-06-01 00:00:00
abstract:PURPOSE:This work explores the distribution of water and its effects on molecular mobilities in poly(vinylpyrrolidone) (PVP) glasses using molecular dynamics (MD) simulation technology. METHODS:PVP glasses containing 0.5% and 10% w/w water and a small amount of ammonia and Phe-Asn-Gly were generated. Physical aging pr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-5277-5
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:Good glycaemic control is essential to minimize the risk for diabetes-induced complications. Also, compliance is likely to be higher if the procedure is simple and painless. This study was designed to validate painless intradermal delivery via a patch-like microneedle array. MATERIALS AND METHODS:Diabetes was ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9256-x
更新日期:2007-07-01 00:00:00
abstract:PURPOSE:To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. METHODS:We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0815-4
更新日期:2012-11-01 00:00:00
abstract:PURPOSE:In the present work, we developed water-in-oil (w/o) nanoemulsions for the intravesical administration of cisplatin. METHODS:The nanoemulsions were made up of soybean oil as the oil phase and Span 80, Tween 80, or Brij 98 as the emulsifier system. alpha-Terpineol and oleic acid were incorporated as permeation ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9947-6
更新日期:2009-10-01 00:00:00
abstract::The permeation enhancing property of 5% oleic acid in ethanol on beta-estradiol was investigated in vitro and in vivo using symmetrical and asymmetrical side-by-side diffusion cells and the human skin sandwich flap, respectively. beta-Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH). Oleic...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018974131236
更新日期:1993-12-01 00:00:00
abstract:PURPOSE:For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of ae...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1992-3
更新日期:2016-11-01 00:00:00
abstract::Many drugs and desirable phytochemicals are bitter, and bitter tastes are aversive. Food and pharmaceutical manufacturers share a common need for bitterness-masking strategies that allow them to deliver useful quantities of the active compounds in an acceptable form and in this review we compare and contrast the chall...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-014-1480-6
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:The study was performed for clarifying the mechanism of interaction between indoxyl sulfate (IS), a typical uremic toxin bound to site II, and site I-ligands when bound to human serum albumin (HSA). The effect of the N to B transition on the interactions was also examined. METHODS:Quantitative investigation of...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011014629551
更新日期:2001-04-01 00:00:00
abstract:PURPOSE:A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT. METHODS:We determined lethality (LD50) of deactivate...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1816-x
更新日期:2016-03-01 00:00:00
abstract:PURPOSE:To better understand the nature of drug-excipient interactions we have studied the phase behavior of amorphous binary and ternary mixtures of citric acid, indomethacin and PVP, as model systems. METHODS:We have prepared amorphous mixtures by co-melting or coprecipitation from solvents, and have measured glass ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011983606606
更新日期:1998-08-01 00:00:00
abstract:PURPOSE:The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. METHODS:Two grades of PLGA, PLGA 7525 [D,L-lactide:glycolide(75:25), MW 90,000-126,000 Da] and Resomer...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-9042-6
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. METHODS:The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in li...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2209-0
更新日期:2017-10-01 00:00:00
abstract:PURPOSE:The purpose of the present study was to investigate the transport of organic monocarboxylic acids mediated by the anion exchanger AE2, which has been already reported to be present at several tissue cell membranes, including intestinal brush border membrane in rabbit. METHODS:Membrane transport of organic mono...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011920213991
更新日期:1998-03-01 00:00:00
abstract:PURPOSE:This study was conducted to assess the pharmacokinetics and pharmacodynamics of 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (NOS). METHODS:Male Sprague-Dawley rats were equipped with peritoneal/ venous cannulae and a microdialysis probe in the hippocampal cortex. Rats receiv...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1013042817281
更新日期:2001-11-01 00:00:00
abstract::The stability of a freeze-dried model protein, ribonuclease A (RNase), was investigated under accelerated storage conditions at 45 degrees C for time periods up to 60 days. Because RNase is a fairly stable molecule around pH 7, lyophilization was performed in phosphate buffers at pH 4.0 or 10.0 to accelerate degradati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015959604616
更新日期:1990-10-01 00:00:00
abstract:PURPOSE:In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products. METHODS:Different sugars as ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1634-1
更新日期:2015-07-01 00:00:00
abstract:PURPOSE:Nine common excipients were examined to determine their ability to cause disproportionation of the HCl salt of a a weakly basic compound. The goal was to determine which excipients were problematic and correlate the results to known properties such as surface pH, slurry pH, or molecular structure. Such a correl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1002-y
更新日期:2013-06-01 00:00:00
abstract::Chimeric L6 is a mouse-human monoclonal antibody specific for tumor cell-associated antigens. The factors affecting the physical and chemical stability of chimeric L6 were assessed at elevated temperatures (30-60 degrees C) and by multiple freezing and thawing. Three routes of degradation were observed: chemical degra...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018948901599
更新日期:1994-05-01 00:00:00