JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs.
Eur J Pharm Biopharm
PUBLISHED: 02-22-2011
Show Abstract
Hide Abstract
The study was performed to evaluate the percutaneous penetration of ketoprofen after transdermal administration using a microdialysis technique in pigs, in comparison with rats. Ketoprofen release from patches was determined by analysis of the remaining drug content after application to hairless rats and pigs. Skin and knee joint penetration of ketoprofen was tested by microdialysis, and recovery was determined by retrodialysis. Residual rates in hairless rats and pigs were 68.1 ± 1.6% and 81.7 ± 4.4%, respectively, at 10h. The average recoveries of ketoprofen over 480 min in the skin and knee joint cases were 72.0 ± 3.4% and 9.8 ± 6.2% in rats and 72.3 ± 2.5% and 57.6 ± 3.1% in pigs, respectively. In rats, ketoprofen was rapidly absorbed with transdermal administration, with C(max) values of 191.7 ± 76.2 and 35.5 ± 21.7 ng/mL and AUC(0-8h) values of 918.2 ± 577.5 and 195.9 ± 137.1 ngh/mL, respectively, for the skin and knee joint. The C(max) values for the pig were 20.9 ± 18.5 and 3.7 ± 3.0 ng/mL, with AUC(0-8h) values of 73.1 ± 69.2 and 16.1 ± 16.1 ngh/mL. Ketoprofen concentrations within skin and knee joint of non-application sites in rats and pigs were less than 0.8 ng/mL. Transdermal administration of ketoprofen significantly reduced prostaglandin E2 levels in the skin of the application site and showed a tendency for inhibition in the knee joint. We thus demonstrated that topical patches containing ketoprofen can deliver the drug through the skin and knee joint of pigs and rats via direct diffusion, and microdialysis data with the pig may be useful for the prediction of human tissue penetration of drugs with transdermal administration.
Related JoVE Video
Surgical venous thrombectomy for Japanese patients with acute deep vein thrombosis: a review of 5 years experience.
J Nippon Med Sch
PUBLISHED: 07-09-2010
Show Abstract
Hide Abstract
Deep vein thrombosis (DVT) is a major risk factor for pulmonary thromboembolism (PTE). We carefully selected patients for surgical thrombectomy to treat acute-phase thrombosis and obtained favorable results.
Related JoVE Video
Oligoarginine-linked polymers as a new class of penetration enhancers.
J Control Release
PUBLISHED: 04-03-2010
Show Abstract
Hide Abstract
Oligoarginines, which are known as cell-penetrating peptides, enhance the cellular uptake of poorly membrane-permeable bioactive molecules that are chemically conjugated to them. We designed a novel polymer: oligoarginine-linked poly(N-vinylacetamide-co-acrylic acid), with the expectation that the polymers will enhance the cellular uptake of the bioactive molecules that are physically mixed with them. Oligoarginines were grafted onto the polymer backbone through the chemical reaction with acrylic acid functional groups. The changes in the blood glucose concentration after nasal administration of insulin with and without the polymer were monitored in mice. The blood glucose concentration was slightly reduced when insulin was given solely at a dose of 10IU/kg. A D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) with a grafting degree of 2% significantly enhanced the insulin-induced hypoglycemic effect. A similar enhancement was not observed when the polymer was substituted with intact D-octaarginine. The penetration-enhancing function of D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) increased dramatically with an increase in the grafting degree of D-octaarginine. Substitution of D-octaarginine with the corresponding optical isomer and an increase in the number of arginine residues rather reduced the penetration-enhancing function. In vitro cell studies also indicated that a D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) with a grafting degree of 17% enabled fluorescein isothiocyanate-dextran to effectively penetrate the cell membrane. Results demonstrated that our oligoarginine-linked polymer has a potential to provide a new class of penetration enhancers.
Related JoVE Video
Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth.
Biochem. Biophys. Res. Commun.
PUBLISHED: 02-24-2010
Show Abstract
Hide Abstract
The androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers. The present study demonstrates that the topoisomerase I inhibitor camptothecin selectively inhibits androgen-responsive growth of prostate cancer cells. Camptothecin strikingly inhibited mutated and wild-type AR protein expression in LNCaP and PC-3/AR cells. This inhibition coincided with decreased androgen-mediated AR phosphorylation at Ser(81) and reduced androgen-mediated AR transcriptional activity in a dose-dependent manner. Additionally, camptothecin disrupted the association between AR and heat shock protein 90 and impeded binding of the synthetic androgen [3H]R1881 to AR in LNCaP cells. Camptothecin also blocked androgen-induced AR nuclear translocation, leading to downregulation of the AR target gene PSA. In addition to decreasing the intracellular and secreted prostate-specific antigen (PSA) levels, camptothecin markedly inhibited androgen-stimulated PSA promoter activity. Collectively, our data reveal that camptothecin not only serves as a traditional genotoxic agent but, by virtue of its ability to target and disrupt AR, may also be a novel candidate for the treatment of prostate cancer.
Related JoVE Video
Photoinflammatory responses to UV-irradiated ketoprofen mediated by the induction of ROS generation, enhancement of cyclooxygenase-2 expression, and regulation of multiple signaling pathways.
Free Radic. Biol. Med.
PUBLISHED: 09-08-2009
Show Abstract
Hide Abstract
Ketoprofen (KP) is photolabile and undergoes degradation when irradiated by sunlight, causing the development of various skin diseases. In this study, we found that UVB-irradiated KP can lead to inflammatory responses mediated by the induction of COX-2 and production of PGE(2). The ability of cells to repair UVB-induced cyclobutane pyrimidine dimers was impaired by UVB-irradiated KP, which consequently facilitated UVB-induced DNA damage to keratinocytes. The reactive oxygen species (ROS) generated by the photodegradation of KP facilitate UVB-induced inflammation and apoptosis in HaCaT cells. Elevation of the COX-2 levels was inhibited by an NADPH oxidase inhibitor and an NF-kappaB inhibitor but was largely enhanced after glutathione depletion by buthionine sulfoximine. Inhibition of ERK1/2, p38, and PI3K signaling attenuated the induction of COX-2, whereas inhibition of JNK signaling by SP600125 had very little effect. UVB-irradiated KP provoked an appreciable accumulation of pSer(15)-p53/COX-2 complexes, but this nuclear association of complexes was partially inhibited by PD98059. Silencing of COX-2 with siRNA was associated with reduced p53 phosphorylation and enhanced KP-photoinduced loss of mitochondrial membrane potential and cleavage of caspase 3 and PARP. This induction of apoptosis was prevented by N-acetylcysteine. In conclusion, this study highlights the particular inflammatory response to a photooxidative drug and suggests that KP-photoinduced inflammatory responses are predominantly attributable to induction of ROS generation and directly impair DNA repair.
Related JoVE Video
p27-Associated G1 arrest induced by hinokitiol in human malignant melanoma cells is mediated via down-regulation of pRb, Skp2 ubiquitin ligase, and impairment of Cdk2 function.
Cancer Lett.
PUBLISHED: 04-30-2009
Show Abstract
Hide Abstract
Increasing evidence has confirmed that hinokitiol (beta-thujaplicin), a tropolone-related compound, exhibits anticancer activity in a variety of cancers through inhibition of cell proliferation. The present study indicates that hinokitiol selectively inhibits cell growth and DNA synthesis in FEM human melanoma cells. Hinokitiol-induced growth inhibition was associated with strong G1 cell cycle arrest. Consistent with blocking the G1-S-phase transition, hinokitiol markedly increased p27 protein levels, but caused only a moderate increase in p21, in addition to a decrease in Cdk2, cyclin E, and phosphorylated Rb. In addition, hinokitiol increased the stability of the p27 protein by inhibiting p27 phosphorylation at Thr(187) and by down-regulating Skp2 expression. siRNA knockdown of p27 abrogated hinokitiol-mediated growth inhibition, while knockdown of Skp2 exacerbated the G1 arrest. In addition to increasing Cdk inhibitor levels and decreasing cyclin A expression, hinokitiol also impaired Cdk2 function by inhibiting Cdk2 kinase activity, impeding cyclin E or A/Cdk2 binding, and inducing translocation of the Cdk2 protein complex. Taken together, our data demonstrate that the novel anticancer mechanism of hinokitiol involves accumulation of p27, down-regulation of Skp2, and impairment of Cdk2 function in FEM human melanoma cells. The therapeutic potential of hinokitiol may lead to novel cell-cycle-based anticancer strategies for malignant melanoma.
Related JoVE Video
Cell-penetrating peptide-linked polymers as carriers for mucosal vaccine delivery.
Mol. Pharm.
Show Abstract
Hide Abstract
We evaluated the potential of poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, as a carrier for mucosal vaccine delivery. Mice were nasally inoculated four times every seventh day with PBS containing ovalbumin with or without the d-octaarginine-linked polymer. The polymer enhanced the production of ovalbumin-specific immunoglobulin G (IgG) and secreted immunoglobulin A (IgA) in the serum and the nasal cavity, respectively. Ovalbumin internalized into nasal epithelial cells appeared to stimulate IgA production. Ovalbumin transferred to systemic circulation possibly enhanced IgG production. An equivalent dose of the cholera toxin B subunit (CTB), which was used as a positive control, was superior to the polymer in enhancing antibody production; however, dose escalation of the polymer overcame this disadvantage. A similar immunization profile was also observed when ovalbumin was replaced with influenza virus HA vaccines. The polymer induced a vaccine-specific immune response identical to that induced by CTB, irrespective of the antibody type, when its dose was 10 times that of CTB. Our cell-penetrating peptide-linked polymer is a potential candidate for antigen carriers that induce humoral immunity on the mucosal surface and in systemic circulation when nasally coadministered with antigens.
Related JoVE Video
Performance of cell-penetrating peptide-linked polymers physically mixed with poorly membrane-permeable molecules on cell membranes.
Eur J Pharm Biopharm
Show Abstract
Hide Abstract
We are investigating a new class of penetration enhancers that enable poorly membrane-permeable molecules physically mixed with them to effectively penetrate cell membranes without their concomitant cellular uptake. Since we previously revealed that poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, significantly enhanced the nasal absorption of insulin, we examined the performance of the polymers on cell membranes. When Caco-2 cells were incubated with 5(6)-carboxyfluorescein (CF) for 30 min, approximately 0.1% of applied CF was internalized into the cells. This poor membrane permeability was dramatically enhanced by d-octaarginine-linked polymers; a 25-fold increase in the cellular uptake of CF was observed when the polymer concentration was adjusted to 0.2mg/mL. None of the individual components, for example, d-octaarginine, had any influence on CF uptake, demonstrating that only d-octaarginine anchored chemically to the polymeric platform enhanced the membrane permeation of CF. The polymer-induced CF uptake was consistently high even when the incubation time was extended to 120 min. Confocal laser scanning microphotographs of cells incubated with d-octaarginine-linked polymers bearing rhodamine red demonstrated that the cell outline was stained with red fluorescence. The polymer-induced CF uptake was significantly suppressed by 5-(N-ethyl-N-isopropyl)amiloride, which is an inhibitor of macropinocytosis. Results indicated that d-octaarginine-linked polymers remained on the cell membrane and poorly membrane-permeable CF was continuously internalized into cells mainly via macropinocytosis repeated for the individual peptidyl branches in the polymer backbone.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.