共查询到20条相似文献,搜索用时 328 毫秒
1.
Fu Chen Zhenshan Jia Kelly C. Rice Richard A. Reinhardt Kenneth W. Bayles Dong Wang 《Pharmaceutical research》2014,31(11):3031-3037
Purpose
The purpose of this study was to develop a novel, drug-free therapy that can reduce the over-accumulation of cariogenic bacteria on dental surfaces.Methods
We designed and synthesized a polyethylene glycol (PEG)-based hydrophilic copolymer functionalized with a pyrophosphate (PPi) tooth-binding anchor using “click” chemistry. The polymer was then evaluated for hydroxyapatite (HA) binding kinetics and capability of reducing bacteria adhesion to artificial tooth surface.Results
The PPi-PEG copolymer can effectively inhibit salivary protein adsorption after rapid binding to an artificial tooth surface. As a result, the in vitro S. mutans adhesion study showed that the PPi-PEG copolymer can inhibit saliva protein-promoted S. mutans adhesion through the creation of a neutral, hydrophilic layer on the artificial tooth surface.Conclusions
The results suggested the potential application of a PPi-PEG copolymer as a drug-free alternative to current antimicrobial therapy for caries prevention. 相似文献2.
Suzanne M. D’Addio John Gar Yan Chan Philip Chi Lip Kwok Bryan R. Benson Robert K. Prud’homme Hak-Kim Chan 《Pharmaceutical research》2013,30(11):2891-2901
Purpose
While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation.Methods
Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying.Results
Spray freeze drying a solution of nanoparticles and mannitol (2 wt% solids) resulted in particles with an average diameter of 21?±?1.7 μm, regardless of the fraction of nanoparticles loaded (0–50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1 μm with hand agitation and to < 250 nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration.Conclusions
This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs. 相似文献3.
Fumie Yamasaki Shoko Machida Asami Nakata Alfarius Eko Nugroho Yusuke Hirasawa Toshio Kaneda Osamu Shirota Naoyuki Hagane Tadayoshi Sugizaki Hiroshi Morita 《Journal of natural medicines》2013,67(1):212-216
Two new isocoumarin glucosides, haworforbins A (1) and B (2), and a new chromone, haworforbin C (3), have been isolated from Haworthia cymbiformis. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Haworforbin C (3) exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cell line. 相似文献
4.
Xihui Gao Jun Qian Shuyan Zheng Ying Xiong Jiahao Man Binxin Cao Lu Wang Shenghong Ju Cong Li 《Pharmaceutical research》2013,30(10):2538-2548
Purpose
To investigate the multivalent effect for up-regulating the intracerebral delivery of nanoparticles via receptor-mediated transcytosis.Methods
Nanoparticles labeled with near-infrared (NIR) fluorophore and different numbers of angiopep-2 peptides that specifically target low-density lipoprotein receptor-related protein (LRP) on the brain capillary endothelial cells were developed. Bio-distribution studies quantified the intracerebral uptakes of these nanoparticles at 2 and 24 h after intravenous injection. In vivo NIR fluorescence imaging, ex vivo autoradiographic imaging and 3D reconstructed NIR fluorescence imaging revealed the nanoparticle distribution pattern in brain. Fluorescence microscopic imaging identified the nanoparticle locations at the cellular level.Results
The multimetirc association between the angiopep-2 peptides labeled on the nanoparticle and the LRP receptors on the brain capillary endothelial cells significantly increased the intracerebral uptake of the nanoparticles. Nanoparticle Den-Angio4 labeled four angiopep-2 peptides achieved the highest BBB traverse efficacy. After penetrating the BBB, Den-Angio4 distributed heterogeneously and mainly located at hippocampus, striatum and cerebellum in the brains.Conclusions
The multivalent effect significantly enhances the BBB permeability of nanoparticles. Den-Angio4 as a nanoparticle prototype provides a two order targeted strategy for diagnosis or treatment of central nerver system diseases by first traversing the BBB via receptor-mediated endocytosis and secondly targeting the leisions with high receptor expression level. 相似文献5.
Neda Samadi Mies J. van Steenbergen Joep B. van den Dikkenberg Tina Vermonden Cornelus F. van Nostrum Maryam Amidi Wim E. Hennink 《Pharmaceutical research》2014,31(10):2593-2604
Purpose
To investigate the effect of polyethylene glycol (PEG) in nanoparticles based on blends of hydroxylated aliphatic polyester, poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and PEG-PLGHMGA block copolymers on their degradation and release behavior.Methods
Protein-loaded nanoparticles were prepared with blends of varying ratios of PEG-PLGHMGA (molecular weight of PEG 2,000 and 5,000 Da) and PLGHMGA, by a double emulsion method with or without using poly(vinyl alcohol) (PVA) as surfactant. Bovine serum albumin and lysozyme were used as model proteins.Results
PEGylated particles prepared without PVA had a zeta potential ranging from ~ ?3 to ~?35 mV and size ranging from ~200 to ~600 nm that were significantly dependent on the content and type of PEG-block copolymer. The encapsulation efficiency of the two proteins however was very low (<30%) and the particles rapidly released their content in a few days. In contrast, all formulations prepared with PVA showed almost similar particle properties (size: ~250 nm, zeta potential: ~?1 mV), while loading efficiency for both model proteins was rather high (80–90%). Unexpectedly, independent of the type of formulation, the nanoparticles had nearly the same release and degradation characteristics. NMR analysis showed almost a complete removal of PEG in 5 days which explains these marginal differences.Conclusions
Protein release and particle degradation are not substantially influenced by the content of PEG, likely because of the fast shedding of the PEG blocks. These PEG shedding particles are interesting system for intracellular delivery of drugs. 相似文献6.
Purpose
We evaluated the controlled release of lysozyme from various poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50-polyethylene glycol (PEG) block copolymers relative to PLGA 50/50.Methods
Lysozyme was encapsulated in cylindrical implants (0.8 mm diameter) by a solvent extrusion method. Release studies were conducted in phosphate buffered saline +0.02% Tween 80 (PBST) at 37°C. Lysozyme activity was measured by a fluorescence-based assay. Implant erosion was evaluated by kinetics of polymer molecular weight decline, water uptake, and mass loss.Results
Lysozyme release from an AB15 di-block copolymer (15% 5 kDa PEG, PLGA 28 kDa) was very fast, whereas an AB10 di-block copolymer (with 10% 5 kDa PEG, PLGA 45 kDa) and ABA10 tri-block copolymer (with 10% 6 kDa PEG, PLGA 27 kDa) showed release profiles similar to PLGA. We achieved continuous lysozyme release for up to 4 weeks from AB10 and ABA10 by lysozyme co-encapsulation with the pore-forming and acid-neutralizing MgCO3, and from AB15 by co-encapsulation of MgCO3 and blending AB15 with PLGA. Lysozyme activity was mostly recovered during 4 weeks.Conclusions
These block co-polymers may have utility either alone or as PLGA blends for the controlled release of proteins. 相似文献7.
8.
Naoki Itoh Eiichi Yamamoto Tomofumi Santa Takashi Funatsu Masaru Kato 《Pharmaceutical research》2016,33(6):1440-1446
Purpose
Nanoparticles have been used in diverse areas, and even broader applications are expected in the future. Since surface modification can influence the configuration and toxicity of nanoparticles, a rapid screening method is important to ensure nanoparticle quality.Methods
We examined the effect of the nanoparticle surface morphology on the HPLC elution profile using two types of 100-nm liposomal nanoparticles (AmBisome? and DOXIL?).Results
These 100-nm-sized nanoparticles eluted before the holdup time (about 4 min), even when a column packed with particles with a relatively large pore size (30 nm) was used. The elution time of the nanoparticles increased with pegylation of the nanoparticles and protein adsorption to the nanoparticles; however, the nanoparticles still eluted before the holdup time.Conclusions
The results of this study indicate that HPLC is a suitable tool for rapid evaluation of the surface of liposomal nanoparticles.9.
Magnetic Targeting of Novel Heparinized Iron Oxide Nanoparticles Evaluated in a 9L-glioma Mouse Model 总被引:1,自引:0,他引:1
Purpose
A novel PEGylated and heparinized magnetic iron oxide nano-platform (DNPH) was synthesized for simultaneous magnetic resonance imaging (MRI) and tumor targeting.Methods
Starch-coated magnetic iron oxide nanoparticles (“D”) were crosslinked, aminated (DN) and then simultaneously PEGylated and heparinized with different feed ratios of PEG and heparin (DNPH1-4). DNPH products were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and superconducting quantum interference device (SQUID). The magentic targeting of DNPH3, with appropriate amounts of conjugated PEG and heparin, in a mouse 9L-glioma subcutaneous tumor model was confirmed by magnetic resonance imaging (MRI)/electron spin resonance (ESR).Results
DNPH3 showed long circulating properties in vivo (half-life >8 h, more than 60-fold longer than that of parent D) and low reticuloendothelial system (RES) recognition in liver and spleen. Protamine, a model cationic protein, was efficiently loaded onto DNPH3 with a maximum loading content of 26.4 μg/mg Fe. Magnetic capture of DNPH3 in tumor site with optimized conditions (I.D. of 12 mg/kg, targeting time of 45 min) was up to 29.42 μg Fe/g tissue (12.26% I.D./g tissue).Conclusion
DNPH3 showed the potential to be used as a platform for cationic proteins for simultaneous tumor targeting and imaging. 相似文献10.
Kohta Mohri Kengo Nagata Shozo Ohtsuki Shiori Toyama Mao Nonomura Yuki Takahashi Yoshinobu Takakura Makiya Nishikawa Shinji Sakuma 《Pharmaceutical research》2017,34(11):2362-2370
Purpose
We previously demonstrated that the immunostimulatory activity of CpG DNA is increased by the formation of polypod-like structures. The present study was designed to elucidate the mechanism underlying this increase.Methods
Tripodna (three pods) and hexapodna (six pods) were prepared. The cellular uptake of Alexa Fluor 488-labeled DNA samples was examined in several cell lines by measuring the MFI of cells. TNF-α release from RAW264.7 cells was measured after addition of polypodna containing CpG motifs. Dissociation of double stranded DNA was evaluated using FRET.Results
Tripodna and hexapodna were efficiently taken up by macrophage-like RAW264.7 cells and dendritic DC2.4 cells, but not by fibroblast or endothelial cell lines. The uptake by RAW264.7 cells was highest for hexapodna, followed by tripodna, dsDNA, and ssDNA. The release of TNF-α from RAW264.7 cells was also highest for hexapodna. The ratio of TNF-α release to cellular uptake was highest for ssDNA, and lowest for dsDNA. Tripodna and hexapodna were more easily dissociated into single strands after cellular uptake than was dsDNA.Conclusions
The efficient cellular uptake and prompt dissociation into single strands can be directly related to the high immunostimulatory activity of polypod-like structured DNAs containing CpG motifs.11.
Rationale
Numerous case reports have suggested that aripiprazole can worsen psychotic symptoms in schizophrenia.Objectives
We reviewed reported cases which have suggested that aripiprazole can worsen psychotic symptoms in schizophrenia and evaluated each regarding quality of the causal relationship.Methods
A systematic literature search was conducted on August 18, 2012, using the PubMed and the EMBASE. Twenty-two cases met the following inclusion criteria: (1) diagnosis of schizophrenia or schizoaffective disorder, (2) worsening of psychotic symptoms associated with aripiprazole, and (3) aripiprazole dose ≤30 mg/day. Information about the causal relationship between aripiprazole and increased psychotic symptoms was extracted. The quality of the causal relationship was evaluated according to the modified guidelines for evaluation of drug-associated events and classified as “questionable,” “moderately suggestive,” or “highly suggestive.”Results
Patients were chronic in at least 15 cases, and prior antipsychotic dose exceeded recommended guidelines in 19 cases. Psychotic symptoms worsened after simply adding aripiprazole to the current regimen in eight cases. Besides psychotic symptoms, increasing agitation (nine cases), aggression (11 cases), and/or activation (seven cases) were reported. Clinical resolution occurred after aripiprazole discontinuation in eight cases. Regarding causal relationship, 11 cases were classified as “highly suggestive,” three as “moderately suggestive,” and eight as “questionable”.Conclusions
Clinicians should be vigilant when adding aripiprazole to patients with chronic schizophrenia also receiving relatively high doses of other antipsychotics, and discontinuation of aripiprazole should be considered if psychotic symptoms and/or agitation/aggression/activation increase. 相似文献12.
Anne-Claire Groo Kristina Mircheva Jérôme Bejaud Caroline Ailhas Ivan Panaiotov Patrick Saulnier Tzvetanka Ivanova Frederic Lagarce 《Pharmaceutical research》2014,31(7):1753-1765
Purpose
To study, diffusion through mucus (3D model) of different formulations of paclitaxel loaded lipid nanocapsules (Ptx-LNCs), to interpret the results in the light of LNC behavior at air-mucus interface (2D model).Methods
LNC surface properties were modified with chitosan or poly(ethylene glycol) (PEG) coatings of different size (PEG 2,000 to 5,000 Da) and surface charges. LNC diffusion through 446 μm pig intestinal mucus layer was studied using Transwell®. LNCs were spread at the air-water-mucus interface then interfacial pressure and area changes were monitored and the efficiency of triglyceride (TG) inclusion was determined.Results
Ptx-LNCs of surface charges ranging from ?35.7 to +25.3 mV were obtained with sizes between 56.2 and 75.1 nm. The diffusion of paclitaxel in mucus was improved after encapsulation in neutral or positively charged particles (p?<?0.05 vs Taxol®). No significative difference was observed in the 2,000–5,000 PEG length for diffusion both on the 2D or 3D models. On 2D model positive or neutral LNCs interacted less with mucus. Highest efficiency of TG inclusion was observed for particles with smallest PEG length.Conclusions
The results obtained with 2D and 3D model allowed us to select the best candidates for in vivo studies (neutral or positive LNCs with smaller PEG length). 相似文献13.
Mohammad Ali Amini Mohammad Ali Faramarzi Dariush Mohammadyani Elina Esmaeilzadeh-Gharehdaghi Amir Amani 《Journal of pharmaceutical innovation》2013,8(2):111-120
Purpose
Artificial neural networks (ANNs) are used to optimize a formulation of poly(lactic acid) (PLA) nanoparticles containing hydrophobic drug molecules through a study of the critical parameters affecting nanoparticle size.Methods
We evaluate the effect of input variables, including concentrations of PLA and Tween 80, amplitude of ultrasound wave, and sonication time on the formation of PLA nanoparticles, which were prepared using a solvent evaporation method. Budesonide was used as a model hydrophobic drug. An ANN model was created using training data and evaluated for prediction capability using validation data.Results
The ANN model demonstrated that reducing PLA concentration and increasing Tween 80 concentration provided optimum conditions for the preparation of small particle size. Additionally, the simultaneous use of high sonication time and amplitude has an adverse effect on particle diameter.Conclusion
By defining the effects of each parameter on the size of PLA nanoparticles, this study demonstrated the feasibility of using an ANN model to optimize the conditions for achieving minimum particle size in hydrophobic drug-loaded PLA nanoparticles. 相似文献14.
Michael Morgen David Tung Britton Boras Warren Miller Anne-Marie Malfait Micky Tortorella 《Pharmaceutical research》2013,30(1):257-268
Purpose
To evaluate using cationic polymeric nanoparticles that interact with hyaluronate to form ionically cross-linked hydrogels to increase the intra-articular retention time of osteoarthritis drugs in the synovial cavity.Methods
In vitro tests included nanoparticle release from cross-linked hydrogels using syringe and membrane dissolution tests, viscosity measurement of synovial fluid containing hydrogels, and release-rate measurement for a model active conjugated to a cationically substituted dextran using a hydrolyzable ester linkage in a sink dissolution test. Nanoparticle retention after intra-articular injection into rat knees was measured in vivo using fluorescence molecular tomography.Results
Diffusional and convective transport of cationic nanoparticles from ionically cross-linked hydrogels formed in synovial fluid was slower in vitro than for uncharged nanoparticles. Hydrogels formed after the nanoparticles were mixed with synovial fluid did not appreciably alter the viscosity of the synovial fluid in vitro. In vitro release of a conjugated peptide from the cationic nanoparticles was approximately 20% per week. After intra-articular injection in rat knees, 70% of the nanoparticles were retained in the joint for 1 week.Conclusions
This study demonstrates the feasibility of using cationic polymeric nanoparticles to increase the retention of therapeutic agents in articular joints for indications such as osteoarthritis. 相似文献15.
Newa M Bhandari KH Tang L Kalvapalle R Suresh M Doschak MR 《Pharmaceutical research》2011,28(5):1131-1143
Purpose
To generate and characterize a specific monoclonal antibody (mAb) against recombinant human RANK receptor and to develop an antiresorptive strategy using this mAb as an osteoclast-targeting platform that selectively targets osteoclast cells whilst delivering an attached (i.e. chemically conjugated) active drug cargo.Methods
Using hybridoma technology, we generated a specific monoclonal antibody (mAb) against recombinant human RANK receptor and characterized by SDS PAGE, ELISA, Western Blot and immunocytochemistry, then synthesized osteoclast-targeting bioconjugates of salmon calcitonin (sCT) using this antibody by generating thiol groups on mAb using 2-Iminothiolane and subsequently reacting them with sCT-PEG-MAL synthesised from sCT and NHS-PEG-MAL. To test the efficacy of the conjugate in vitro, osteoclasts were generated from precursor RAW 264.7 cells by dosing with the cytokines macrophage-colony-stimulating factor (M-CSF), and RANK Ligand (RANKL) and TRAP activity assay, Resorption Pit Assay, TRAP staining were performed. Cytotoxicity of the mAb-sCT conjugate was also evaluated in RAW 264.7 cells; sCT bioactivity and CTR binding potential were evaluated by in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells.Results
Generation of antibody against human RANK receptor was confirmed by SDS PAGE, ELISA and Western Blot. Immunocytochemistry confirmed the osteoclast targeting potential of the antibody. Successful conjugation of the antibody with sCT was confirmed by SDS PAGE and ELISA.Multinucleated osteoclast formation was confirmed by staining for tartrate-resistant acid phosphatase (TRAP). Conjugate functionality was confirmed by TRAP activity and Resorption Pit assay, showing the inhibitory effect on osteoclast differentiation. cAMP assay confirmed the retention of calcitonin bioactivity after conjugation.Conclusions
Our strategy offers the potential for a ??universal?? osteoclast-targeting platform??one that targets the RANK receptor on osteoclast cells by simply altering the conjugated cargo in order to affect the specific regulation of osteoclast cells. 相似文献16.
Ioan Sporea Alina Popescu Mircea Focşa Gabriel Becheanu Roxana Şirli Maria Cornianu Liana Gheorghe Cristina Cijevschi Prelipcean Cătălina Mihai Ion Rogoveanu Larisa Săndulescu 《Central European Journal of Medicine》2013,8(5):669-673
Aim
We evaluated the influence of the type of needle and the operator’s experience on the quality of the specimen obtained at liver biopsy (LB).Material and method
We performed a multicentre, prospective study in four university hospitals, including LBs performed using either “cutting” (TruCut) or “suction” (Menghini) needles. According to their experience, we considered the operators as “junior” (<100 LBs) or “senior” (>100 LBs).Results
A total number of 745 LBs were evaluated, 413 performed with suction needles and 332 with cutting needles. Of all LBs, 473 where performed by “senior” and 272 by “junior” operators. The mean length of the fragment obtained was larger in LBs performed by senior (23.5±11.6 mm) vs. junior operators (15.9±9.8 mm, p<0.001) and also if modified Menghini needles were used (23.7±12.1 mm) vs. TruCut (13.0±5.2 mm, p<0.001). The number of portal tracts (PT) was higher in LBs performed by “senior” (14.3±8.8 PT) vs. “junior” operators (8.8±6.8 PT, p<0.001); and with Menghini needles (17.2±9.7 PT) vs. TruCut (8.6±5.0 PT, p<0.001).Conclusion
Our study demonstrates that optimal biopsy samples are obtained by two intrahepatic passages with Menghini needles and that “senior” operators obtain better tissue samples than “junior” ones. 相似文献17.
Christopher R. DeWitt Kennon Heard Javier C. Waksman 《Journal of medical toxicology》2007,3(3):107-118
Objectives
We will describe insulin and C-peptide levels observed in sulfonylurea-induced hypoglycemia and determine whether these levels differed if obtained before or after hypoglycemic therapy.Methods
We performed a systematic review of the English literature to identify Medline articles containing “sets” (glucose < 60 mg/dL with insulin and C-peptide levels). These “sets” were categorized as being obtained BEFORE, AFTER, or UNKNOWN with respect to hypoglycemic therapy.Results
22 articles, 76 patients, and 97 “sets” were included. Mean glucose (mg/dL), insulin (μIU/mL), and C-peptide (ng/mL) for all “sets” were 28.6 (±12.6; 26.1 to 31.2), 54.4 (±126.3; 28.3 to 80.5), 7.2 (±6.2; 5.9 to 8.5).- The BEFORE measures were 24.3 (±7.3; 18.7 to 30.0), 36.6 (±26.2; 16.5 to 56.7), 5.4 (±4.6; 1.5 to 9.2).
- The AFTER measures were 33.1 (±9.8; 28.2 to 38.0), 126.7 (±278.1; 0 to 265.0), 10.3 (±10.5; 5.1 to 15.4).
- The UNKNOWN measures were 28.0 (±13.5; 24.7 to 31.3), 37.1 (±21.8; 31.7 to 42.5), 6.5 (±4.3; 5.4 to 7.6).
- Only one “set” (glucose 49 mg/dL) had insulin < 3.9 μIU/mL and C-peptide < 1.4 ng/mL.
Conclusions
Insulin ≥ 3.9 μIU/mL, C-peptide ≥ 1.4 ng/mL, and glucose < 49 mg/dl are consistent with sulfonylurea-induced hypoglycemia. BEFORE levels were lower, but they were consistent with sulfonylurea-induced hypoglycemia. 相似文献18.
Dong-Sung Lee Xiang Cui Wonmin Ko Kyoung-Su Kim Il Chan Kim Joung Han Yim Ren-Bo An Youn-Chul Kim Hyuncheol Oh 《Archives of pharmacal research》2014,37(8):983-991
In this study, we isolated a new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid (1), from the sea urchin collected from the Sea of Okhotsk. We established the structure of this new compound by analysis of NMR and HRMS data, along with comparison of the data with those of the related compounds reported in the literature. In addition, we investigated its anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages. Compound 1 inhibited the production of NO, iNOS, PGE2, and COX-2, and it also suppressed the production of pro-inflammatory cytokines, such as TNF-α and IL-1β. It inhibited the translocation of the NF-κB subunit p65 into the nucleus by interrupting the phosphorylation and degradation of IκB-α. In addition, compound 1 significantly decreased the phosphorylation of JNK and p38 in LPS-stimulated RAW264.7 macrophages, suggesting that suppression of the inflammation process by compound 1 was mediated through the MAPK pathway. Taken together, this study showed that the anti-inflammatory effects of a new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid were mediated through the inhibition of NF-κB and JNK/p38 MAPK signaling pathways. 相似文献
19.
Michael E. Saladin Kevin M. Gray Aimee L. McRae-Clark Steven D. LaRowe Sharon D. Yeatts Nathaniel L. Baker Karen J. Hartwell Kathleen T. Brady 《Psychopharmacology》2013,226(4):721-737
Rationale/objectives
This study examined the effects of propranolol vs. placebo, administered immediately after a “retrieval” session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent “test” session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up.Methods
CD participants received either 40 mg propranolol or placebo immediately following a “retrieval” CCE session. The next day, participants received a “test” session of CCE that was identical to the “retrieval” session except no medication was administered. Participants underwent a “follow-up” CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions.Results
Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use.Conclusions
This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted. 相似文献20.
Zhang Jun Qing Wang Yong Li Yong Hui Lai Wei Yong Li Hai Long Duan Jin Ao Pei Li Xia 《Archives of pharmacal research》2012,35(12):2143-2146
Chemical investigation of the fruits of Alpinia oxyphylla led to an isolation of the two new natural products, 9-hydroxy epinootkatol (1) and (S)-2-pentanol-2-O-β-D-glucopyranoside (2), in addition to the nine known compounds, pinocembrin (3), tectochrysin (4), izalpinin (5), nookatone (6), yakuchinone A (7), protocatechuic acid (8), β-sitosterol (9), daucosterol (10) and β-sitosterol palmitate (11). Their structures were elucidated on the basis of physicochemical constants and NMR spectral data analysis. The effects of the isolated components on nitric oxide production in LPS-induced RAW 264.7 macrophages were examined. The two new natural compounds showed inhibitory activities with IC50 values of 21.8 and 32.8 μg/mL, respectively. 相似文献