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.
IGF-1 gene expression is differentially regulated by estrogen receptors ? and ? in mouse endometrial stromal cells and ovarian granulosa cells.
J. Reprod. Dev.
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive functions in rats and mice. IGF-1 expression is regulated by estrogen in several reproductive organs including the uterus and ovary. Two types of estrogen receptor (ER? and ER?) are expressed in mouse uteri and ovaries, and it is unclear whether they differently mediate IGF-1 gene transcription. To clarify the roles of ER? and ER?, mouse endometrial stromal cells and ovarian granulosa cells were treated with ligands specific for individual estrogen receptors. In endometrial stromal cells, propyl-pyrazole-triol (PPT; ER?-selective agonist) increased Igf1 mRNA expression, which was suppressed by methyl-piperidino-pyrazole (MPP, ER?-selective antagonist), while diarylpropionitrile (DPN, ER?-potency selective agonist) increased Igf1 mRNA expression, which was inhibited by MPP but not by 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-?]pyrimidin-3-yl]phenol (PHTPP; ER? antagonist). PHTPP enhanced the DPN-induced increase in Igf1 mRNA expression. In ovarian granulosa cells, E2 and DPN decreased Igf1 mRNA expression, whereas PPT did not affect Igf1 mRNA levels. In these cells, PHTPP inhibited the DPN-induced decrease in Igf1 mRNA expression. These results suggest that ER? facilitates Igf1 transcription, whereas ER? appears to inhibit Igf1 gene transcription in mouse endometrial stromal cells and ovarian granulosa cells.
Related JoVE Video
Investigation of the safety of topical metronidazole from a pharmacokinetic perspective.
Biol. Pharm. Bull.
PUBLISHED: 01-11-2013
Show Abstract
Hide Abstract
Metronidazole (MTZ) ointment has been used widely as a hospital preparation against cancerous malodor. Although cancerous tissue with ulcer-like symptoms is likely to have a higher capacity to absorb drugs than normal skin, the extent to which MTZ is absorbed when a topical preparation is applied to cancerous tissue remains unclear. Furthermore, few studies have investigated the drug interactions involving MTZ despite its long use in clinical practice. In the present study, plasma concentration of MTZ was measured in a breast cancer patient using MTZ ointment for cancerous malodor and basic research was also conducted with the objective of investigating the safety of topical MTZ from a pharmacokinetic perspective. 4.75?µg/mL (27.8?µM) of MTZ was detected in the patients plasma, which was close to the plasma concentration after oral dosage of MTZ. In a metabolic inhibition study using human liver microsomes, cytochrome P450 (CYP) 2C9-mediated hydroxylation of S-warfarin was almost unaffected by MTZ at the corresponding concentrations. In addition, 3-d repeated oral administration of MTZ (200?mg/kg/d) to rats did not show any significant effects on the hepatic mRNA levels of various CYP isozymes and CYP2C protein levels. These results suggest that the reported interaction of oral MTZ and S-warfarin was not due to CYP2C9 inhibition and that drug interactions via inhibition of CYP2C9 is unlikely to occur when MTZ ointment is applied to ulcerous skin. This information should be valuable for assessing the safety of MTZ ointment used for mitigating cancerous malodor.
Related JoVE Video
Bridging from preclinical to clinical studies for tyrosine kinase inhibitors based on pharmacokinetics/pharmacodynamics and toxicokinetics/toxicodynamics.
Drug Metab. Pharmacokinet.
PUBLISHED: 09-06-2011
Show Abstract
Hide Abstract
The purpose of this study was to provide a pharmacokinetics/pharmacodynamics and toxicokinetics/toxicodynamics bridging of kinase inhibitors by identifying the relationship between their clinical and preclinical (rat, dog, and monkey) data on exposure and efficacy/toxicity. For the eight kinase inhibitors approved in Japan (imatinib, gefitinib, erlotinib, sorafenib, sunitinib, nilotinib, dasatinib, and lapatinib), the human unbound area under the concentration-time curve at steady state (AUC(ss,u)) at the clinical dose correlated well with animal AUC(ss,u) at the no-observed-adverse-effect level (NOAEL) or maximum tolerated dose (MTD). The best correlation was observed for rat AUC(ss,u) at the MTD (p < 0.001). E(max) model analysis was performed using the efficacy of each drug in xenograft mice, and the efficacy at the human AUC of the clinical dose was evaluated. The predicted efficacy at the human AUC of the clinical dose varied from far below E(max) to around E(max) even in the tumor for which use of the drugs had been accepted. These results suggest that rat AUC(ss,u) at the MTD, but not the efficacy in xenograft mice, may be a useful parameter to estimate the human clinical dose of kinase inhibitors, which seems to be currently determined by toxicity rather than efficacy.
Related JoVE Video
Identification of mammalian Pit-1w, possibly involved in spermatogenesis in mice.
Gen. Comp. Endocrinol.
PUBLISHED: 04-06-2011
Show Abstract
Hide Abstract
Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Alternative splicing of Pit-1 gene transcripts has been shown to give rise to several variants with discrete transactivation properties; however, those arising from alternative promoters such as avian Pit-1 w have not yet been identified in mammals. Here, comparative genomics analysis followed by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of 5 cDNA ends (5RACE) were used in identifying Pit-1 w mRNA in the mouse pituitary. The mouse Pit-1 w mRNA is generated by using an alternative promoter located in the first intron, as with chicken Pit-1 w, and is expressed in a wide variety of tissues besides the pituitary. In the testis, Pit-1 w is expressed as the predominant variant and a protein of 33 kDa. During the first wave of spermatogenesis, expression of Pit-1 w mRNA at substantial levels was observed from 3 weeks, but not at 1 or 2 weeks after birth. A combination of immunohistochemistry and in situ hybridization detected Pit-1 mRNA and Pit-1 immunoreactivity in the spermatogonia, spermatocytes, and spermatids in the testis of adult mice. Because secondary spermatocytes and haploid spermatids increase in number between 18 and 20 days after birth in mice, it is possible that mouse Pit-1 w plays a role in spermatogenesis. This is the first report demonstrating the expression of Pit-1 variants arising from alternative promoters in mammals.
Related JoVE Video
Effects of magnesium sulphate administration on aquaporin 3 in rat gastrointestinal tract.
Biol. Pharm. Bull.
PUBLISHED: 03-19-2011
Show Abstract
Hide Abstract
Aquaporin (AQP) 3 plays an important role in regulating faecal water content in the colon. We investigated the role of AQP3 in the colon in the laxative effect of magnesium sulphate (MgSO(4)), a widely used osmotic laxative. Rats were administered MgSO(4), after which faecal water content, the colon mRNA expression levels of sodium myo-inositol transporter (SMIT) and taurine transporter (TauT), the colon protein expression levels of AQP3 were examined. Faecal water content increased over time after MgSO(4) administration, and severe diarrhoea was observed between 4 and 8 h after administration. The mRNA expression levels of SMIT and TauT, which are indicators of variations in osmotic pressure, were highest at 2 h after the administration of MgSO(4) and were still elevated at 8 h after administration when compared to immediately after the administration. The immunostaining analysis showed that AQP3 is a dominant AQP in the rat colon. The protein expression levels of AQP3 in the colon increased over time following the administration of MgSO(4) and at 8 h after administration were approximately 8 times higher than baseline levels. Previously, osmotic laxatives were believed to induce diarrhoea by elevating the osmotic pressure in the intestinal tract. The results of the present study suggest that the laxative effect of MgSO(4) is not simply caused by a change in the osmotic pressure in the intestinal tract, but could be a response to increased expression of AQP3.
Related JoVE Video
A mechanism by which the osmotic laxative magnesium sulphate increases the intestinal aquaporin 3 expression in HT-29 cells.
Life Sci.
PUBLISHED: 05-25-2010
Show Abstract
Hide Abstract
We have suggested that an osmotic laxative, magnesium sulphate (MgSO(4)), may act as a cathartic in a very rational manner by increasing the aquaporin 3 (AQP3) expression level and by changing osmotic pressure in the colon. In this study, we examined the mechanism by which MgSO(4) increases the intestinal AQP3 expression level by using the human colon cancer HT-29 cell line.
Related JoVE Video
Ciprofloxacin suppresses Cyp3a in mouse liver by reducing lithocholic acid-producing intestinal flora.
Drug Metab. Pharmacokinet.
PUBLISHED: 07-03-2009
Show Abstract
Hide Abstract
Ciprofloxacin (CPX), a new quinolone antibiotic, is reported to reduce CYP3A expression in the liver when administered to rats. The present study investigates whether the reduction in intestinal flora is involved in this reduction of CYP3A. While hepatic Cyp3a11 expression and triazolam metabolic activity were significantly reduced by CPX treatment of SPF mice, no significant changes were seen by CPX treatment of germ-free (GF) mice. Lithocholic acid (LCA)-producing bacteria in the feces as well as hepatic level of taurine conjugate of LCA were significantly reduced in CPX-treated SPF mice. Cyp3a11 expression in GF mice was significantly elevated when treated with LCA, known as an activator of fernesoid X receptor and pregnane X receptor. These results indicate that antibiotics such as CPX, having antimicrobial spectrums against LCA-producing bacteria, possibly cause decrease in LCA in the liver, resulting in lower CYP3A expression. The intestinal flora is reported to be altered also by stress, disease and age etc. The findings of the present study suggest that these changes in intestinal flora may modify CYP expression and contribute to individual differences in pharmacokinetics.
Related JoVE Video
Antibiotics suppress Cyp3a in the mouse liver by reducing lithocholic acid-producing intestinal flora.
Yakugaku Zasshi
PUBLISHED: 05-08-2009
Show Abstract
Hide Abstract
We previously demonstrated that ciprofloxacin (CPX), a new quinolone antibiotic, suppresses Cyp3a in the mouse liver by reducing the hepatic level of lithocholic acid (LCA) produced by intestinal flora. The present study investigated the possibility that other antibiotics with antibacterial activity against LCA-producing bacteria also cause a decrease in the LCA level in the liver, leading to reduced expression of Cyp3a11. While the mRNA expression of Cyp3a11 in the liver was significantly reduced when SPF mice were administered antibiotics such as ampicillin, CPX, levofloxacin, or a combination of vancomycin and imipenem, no significant changes were observed after antibiotic treatment of GF mice lacking intestinal flora. LCA-producing bacteria in the feces as well as the hepatic level of the taurine conjugate of LCA were significantly reduced in the antibiotic-treated SPF mice, suggesting that the decrease in Cyp3a11 expression can be attributed to the reduction in LCA-producing intestinal flora following antibiotic administration. These results suggest that the administration of antibiotics with activity against LCA-producing bacteria can also cause a decrease in the LCA level in humans, which may lower CYP3A4 expression. The intestinal flora are reported to be altered not only by drugs, such as antibiotics, but also by stress, disease, and age. The findings of the present study suggest that these changes in intestinal flora could modify CYP expression and contribute to the individual differences in pharmacokinetics.
Related JoVE Video
Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes.
Drug Metab. Dispos.
Show Abstract
Hide Abstract
The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil. The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition. Firstly, the plasma concentration profiles of inhibitors (itraconazole, gemfibrozil, and gemfibrozil glucuronide) were reproduced by a PBPK model to obtain their pharmacokinetic parameters. The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by itraconazole, mechanism-based inhibition of CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting polypeptide (OATP) 1B1 by gemfibrozil and its glucuronide. The plasma concentration profiles of repaglinide were well reproduced by the PBPK model based on the above assumptions, and the optimized values for the inhibition constants (0.0676 nM for itraconazole against CYP3A4; 14.2 ?M for gemfibrozil against OATP1B1; and 5.48 ?M for gemfibrozil glucuronide against OATP1B1) and the fraction of repaglinide metabolized by CYP2C8 (0.801) were consistent with the reported values. The validity of the obtained parameters was further confirmed by sensitivity analyses and by reproducing the repaglinide concentration increase produced by concomitant gemfibrozil administration at various timings/doses. The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the coadministered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide.
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.