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Sample records for carbamazepine affects embryonic

  1. Carbamazepine

    Science.gov (United States)

    ... Adasuve); certain medications to treat malaria such as chloroquine (Aralen) and mefloquine ; medications for anxiety or mental ... pills, patches, rings, injections, implants, or intrauterine devices). Use another form of birth control while taking carbamazepine. ...

  2. Carbamazepine (Tegretol) and Pregnancy

    Science.gov (United States)

    ... take. Can taking carbamazepine during pregnancy affect my baby’s development? More studies are needed before we can be ... taking carbamazepine monotherapy does not appear to affect infant growth or development. Some healthcare providers can measure levels of carbamazepine ...

  3. Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring.

    Science.gov (United States)

    Andretta, Rhayza Roberta; Okada, Fatima Kazue; Paccola, Camila Cicconi; Stumpp, Taiza; de Oliva, Samara Urban; Miraglia, Sandra M

    2014-04-01

    Carbamazepine (CBZ) is an anti-epileptic drug that acts on Leydig cells, affecting steroidogenesis and causes fetal malformation. The aim of this study was to investigate the effects of CBZ on male sexual maturation and other male parameters. Rat dams were treated with CBZ during pregnancy and breastfeeding. The anogenital distance (AGD) and the anogenital index (AGI) were obtained. Testicular descent and preputial separation were also evaluated. The offspring was euthanized at PND 41 and 63. The accessory glands were weighed and the testes were collected for histopathological, morphometric and sterological analyses. The numerical density of Leydig cells and hormone dosage were obtained. CBZ caused an increase of AGI and a delay of testicular descent and of preputial separation. CBZ also caused a decrease of testosterone level and of sperm count and an increase of abnormal sperm. These results indicate that CBZ delays puberty onset and affects steroidogenesis and sperm quality. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Cadmium affects retinogenesis during zebrafish embryonic development

    International Nuclear Information System (INIS)

    Hen Chow, Elly Suk; Yu Hui, Michelle Nga; Cheng, Chi Wa; Cheng, Shuk Han

    2009-01-01

    Ocular malformations are commonly observed in embryos of aquatic species after exposure to toxicants. Using zebrafish embryos as the model organism, we showed that cadmium exposure from sphere stage (4 hpf) to end of segmentation stage (24 hpf) induced microphthalmia in cadmium-treated embryos. Embryos with eye defects were then assessed for visual abilities. Cadmium-exposed embryos were behaviorally blind, showing hyperpigmentation and loss of camouflage response to light. We investigated the cellular basis of the formation of the small eyes phenotype and the induction of blindness by studying retina development and retinotectal projections. Retinal progenitors were found in cadmium-treated embryos albeit in smaller numbers. The number of retinal ganglion cells (RGC), the first class of retinal cells to differentiate during retinogenesis, was reduced, while photoreceptor cells, the last batch of retinal neurons to differentiate, were absent. Cadmium also affected the propagation of neurons in neurogenic waves. The neurons remained in the ventronasal area and failed to spread across the retina. Drastically reduced RGC axons and disrupted optic stalk showed that the optic nerves did not extend from the retina beyond the chiasm into the tectum. Our data suggested that impairment in neuronal differentiation of the retina, disruption in RGC axon formation and absence of cone photoreceptors were the causes of microphthalmia and visual impairment in cadmium-treated embryos

  5. Nail changes after carbamazepine

    Directory of Open Access Journals (Sweden)

    Chopra Adarsh

    2000-01-01

    Full Text Available Antiepileptics are known to produce different types of side effects including nail changes. A 20-year-old epileptic man had yellowish discolouration followed by dystrophy and onycholysis of his 15 nails after taking carbamazepine for 3 months which cleared within six months after discontinuation of the drug. This type of change has not been reported earlier with carbamazepine

  6. High-throughput identification of small molecules that affect human embryonic vascular development

    NARCIS (Netherlands)

    Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R.; Honório, Inês; De Vries, Margreet R.; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H.A.; Pereira, Carlos F.; Mercader, Nadia; Fernandes, Hugo; Ferreira, Lino

    2017-01-01

    Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach

  7. How does blastomere removal affect embryonic development? : A time-lapse analysis

    DEFF Research Database (Denmark)

    Kirkegaard, Kirstine; Hindkjær, Johnny Juhl; Ingerslev, Hans Jakob

    of the 6-10 cell embryo. It has been argued that blastomere removal does not affect embryonic development, but few studies have focussed on safety of the procedure. Recently, time-lapse studies on mice have suggested that blastomere removal affects embryonic development. The present study was conducted...... to evaluate the effect of blastomere biopsy on early human embryonic development using time-lapse analysis. Materials and methods: Couples undergoing IVF treatment or PGD were requested permission to include embryos in the project. The diagnosis healthy/diseased was made by analysis of a single blastomere....... For PGD 56 human embryos were biopsied 68 hours after fertilisation, the majority at the eight cell stage. As controls 43 non-biopsied embryos at the 6-8 cell stage were selected. All embryos were cultured until 5 days after fertilisation in a time-lapse incubator (EmbryoScope™). Key events such as time...

  8. Laser fusion of mouse embryonic cells and intra-embryonic fusion of blastomeres without affecting the embryo integrity.

    Science.gov (United States)

    Krivokharchenko, Alexander; Karmenyan, Artashes; Sarkisov, Oleg; Bader, Michael; Chiou, Arthur; Shakhbazyan, Avetik

    2012-01-01

    Manipulation with early mammalian embryos is the one of the most important approach to study preimplantation development. Artificial cell fusion is a research tool for various biotechnological experiments. However, the existing methods have various disadvantages, first of them impossibility to fuse selected cells within multicellular structures like mammalian preimplantation embryos. In our experiments we have successfully used high repetition rate picosecond near infrared laser beam for fusion of pairs of oocytes and oocytes with blastomeres. Fused cells looked morphologically normal and keep their ability for further divisions in vitro. We also fused two or three blastomeres inside four-cell mouse embryos. The presence of one, two or three nuclei in different blastomeres of the same early preimplantation mouse embryo was confirmed under UV-light after staining of DNA with the vital dye Hoechst-33342. The most of established embryos demonstrated high viability and developed in vitro to the blastocyst stage. We demonstrated for the first time the use of laser beam for the fusion of various embryonic cells of different size and of two or three blastomeres inside of four-cell mouse embryos without affecting the embryo's integrity and viability. These embryos with blastomeres of various ploidy maybe unique model for numerous purposes. Thus, we propose laser optical manipulation as a new tool for investigation of fundamental mechanisms of mammalian development.

  9. Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion

    Directory of Open Access Journals (Sweden)

    Jason L. Russell

    2015-01-01

    Full Text Available Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity.

  10. Mental disorders induced by carbamazepine.

    Science.gov (United States)

    Mizukami, K; Naito, Y; Yoshida, M; Nakanishi, T; Koizumi, J

    1990-03-01

    We present here a case with various physical and neuropsychiatric symptoms caused by the administration of carbamazepine. The patient suffering from right ophthalmic neuralgia showed fever, eczema, erythema, lymphoadenopathy, eosinophilia, vomiting, headache, dizziness, nystagmus, and various mental disorders which consisted of emotional instability, personality change, delusions of reference and persecution, depressive state, and hyperventilation syndrome during the administration of carbamazepine. The physical symptoms in the present case were conformable to the side effect of carbamazepine. The mental disorders appeared in a few days from the start of carbamazepine administration and disappeared after the discontinuation of the administration of this drug without antipsychotic therapy and have never relapsed until now. The mental disorders and the physical symptoms were in parallel with their clinical course. This kind of mental disorders induced by carbamazepine has not yet been reported.

  11. FMR1 epigenetic silencing commonly occurs in undifferentiated fragile X-affected embryonic stem cells.

    Science.gov (United States)

    Avitzour, Michal; Mor-Shaked, Hagar; Yanovsky-Dagan, Shira; Aharoni, Shira; Altarescu, Gheona; Renbaum, Paul; Eldar-Geva, Talia; Schonberger, Oshrat; Levy-Lahad, Ephrat; Epsztejn-Litman, Silvina; Eiges, Rachel

    2014-11-11

    Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from epigenetic silencing of the X-linked FMR1 gene by a CGG expansion in its 5'-untranslated region. Taking advantage of a large set of FXS-affected human embryonic stem cell (HESC) lines and isogenic subclones derived from them, we show that FMR1 hypermethylation commonly occurs in the undifferentiated state (six of nine lines, ranging from 24% to 65%). In addition, we demonstrate that hypermethylation is tightly linked with FMR1 transcriptional inactivation in undifferentiated cells, coincides with loss of H3K4me2 and gain of H3K9me3, and is unrelated to CTCF binding. Taken together, these results demonstrate that FMR1 epigenetic gene silencing takes place in FXS HESCs and clearly highlights the importance of examining multiple cell lines when investigating FXS and most likely other epigenetically regulated diseases.

  12. FMR1 Epigenetic Silencing Commonly Occurs in Undifferentiated Fragile X-Affected Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Michal Avitzour

    2014-11-01

    Full Text Available Fragile X syndrome (FXS is the most common heritable form of cognitive impairment. It results from epigenetic silencing of the X-linked FMR1 gene by a CGG expansion in its 5′-untranslated region. Taking advantage of a large set of FXS-affected human embryonic stem cell (HESC lines and isogenic subclones derived from them, we show that FMR1 hypermethylation commonly occurs in the undifferentiated state (six of nine lines, ranging from 24% to 65%. In addition, we demonstrate that hypermethylation is tightly linked with FMR1 transcriptional inactivation in undifferentiated cells, coincides with loss of H3K4me2 and gain of H3K9me3, and is unrelated to CTCF binding. Taken together, these results demonstrate that FMR1 epigenetic gene silencing takes place in FXS HESCs and clearly highlights the importance of examining multiple cell lines when investigating FXS and most likely other epigenetically regulated diseases.

  13. Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty

    Directory of Open Access Journals (Sweden)

    Saenko Suzanne V

    2010-08-01

    Full Text Available Abstract Background The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity. Results We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling. Conclusions This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling. Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a

  14. Stevens-Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2011-01-01

    Full Text Available Carbamazepine and other anticonvulsants are commoner cause of severe adverse cutaneous drug reactions such as erythema multiforme, toxic epidermal necrolysis (TEN, and Stevens-Johnson syndrome (SJS. We report a case of SJS rapidly progressing to TEN with a combination of haloperidol and carbamazepine in a patient with bipolar affective disorder. The pathophysiological mechanism underlying this reaction is discussed.

  15. A genetic screen for mutations affecting embryonic development in medaka fish (Oryzias latipes).

    Science.gov (United States)

    Loosli, F; Köster, R W; Carl, M; Kühnlein, R; Henrich, T; Mücke, M; Krone, A; Wittbrodt, J

    2000-10-01

    In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.

  16. Inhibition of chondroitin sulfate glycosaminoglycans incorporation affected odontoblast differentiation in cultured embryonic mouse molars.

    Science.gov (United States)

    Liu, Lipei; Chen, Weiting; Li, Lefeng; Xu, Fangfang; Jiang, Beizhan

    2017-12-01

    Chondroitin sulfate proteoglycan (CSPG) is an important component of extracellular matrix (ECM), it is composed of a core protein and one or more chondroitin sulfate glycosaminoglycan side chains (CS-GAGs). To investigate the roles of its CS-GAGs in dentinogenesis, the mouse mandibular first molar tooth germs at early bell stage were cultivated with or without β-xyloside. As expected, the CS-GAGs were inhibited on their incorporation to CSPGs by β-xyloside, accompanied by the change of morphology of the cultured tooth germs. The histological results and the transmission electron microscopy (TEM) investigation indicated that β-xyloside exhibited obvious inhibiting effects on odontoblasts differentiation compared with the control group. Meanwhile the results of immunohistochemistry, in situ hybridization and quantitative RT-PCR for type I collagen, dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein, the products of differentiated odontoblasts, further proved that odontoblasts differentiation was inhibited. Collagen fibers detected in TEM decreased and arranged in disorder as well. Thus we conclude that the inhibition of CS-GAGs incorporation to CSPGs can affect odontoblast differentiation in cultured embryonic mouse molars.

  17. Extracorporeal treatment for carbamazepine poisoning

    DEFF Research Database (Denmark)

    Ghannoum, Marc; Yates, Christopher; Galvao, Tais F

    2014-01-01

    in carbamazepine poisoning. METHODS: After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness......-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR...... is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D...

  18. Compound list: carbamazepine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available carbamazepine CBZ 00018 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Huma...n/in_vitro/carbamazepine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vitro/carbamazepine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vivo/Liver/Single/carbamazepine.Rat.in_vivo.Liver.Single.zip ftp://ftp.bioscienc

  19. Parental and embryonic experiences with predation risk affect prey offspring behaviour and performance.

    Science.gov (United States)

    Donelan, Sarah C; Trussell, Geoffrey C

    2018-03-14

    Because phenotypic plasticity can operate both within and between generations, phenotypic outcomes are often shaped by a complex history of environmental signals. For example, parental and embryonic experiences with predation risk can both independently and interactively influence prey offspring traits early in their life. Parental and embryonic risk experiences can also independently shape offspring phenotypes throughout an offspring's ontogeny, but the persistence of their interactive effects throughout offspring ontogeny is unknown. We examined the effects of parental and embryonic experiences with predation risk on the response of 1-year-old prey (the carnivorous snail, Nucella lapillus ) offspring to current predation risk. We found that parental and embryonic risk experiences had largely independent effects on offspring performance and that these effects were context dependent. Parental experience with risk had strong impacts on multiple offspring traits in the presence of current risk that generally improved offspring performance under risk, but embryonic risk experience had relatively weaker effects and only operated in the absence of current risk to reduce offspring growth. These results illustrate that past environmental experiences can dynamically shape organism phenotypes across ontogeny and that attention to these effects is key to a better understanding of predator/prey dynamics in natural systems. © 2018 The Author(s).

  20. WITHDRAWN: Carbamazepine for cocaine dependence.

    Science.gov (United States)

    Lima Reisser, Anelise A R L; Silva de Lima, Mauricio; Soares, Bernardo Garcia de Oliveira; Farrell, Michael

    2009-01-21

    Cocaine dependence has become a public health problem, developing a significant number of medical, psychological and social problems. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorders, has been used for treatment of cocaine dependence, although its effectiveness has not been established. To determine whether carbamazepine is effective for the treatment of cocaine dependence. We searched: Cochrane Controlled Trials Register (Cochrane Library issue 1, 1999), MEDLINE (f1966 - October 1997), EMBASE (1980 - October 1997), PsycLIT (1974 - July 1997), Biological Abstracts and LILACS (1982 - 1997); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. The specialised register of trials of Cochrane Group on Drugs and Alcohol until February 2003. All randomised controlled trials focused on the use of carbamazepine versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. The reviewers extracted the data independently, Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. 5 studies were included (455 participants). No differences regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety

  1. Intravenous Carbamazepine for Adults With Seizures.

    Science.gov (United States)

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

    2018-03-01

    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  2. Adsorption of carbamazepine by carbon nanotubes: Effects of DOM introduction and competition with phenanthrene and bisphenol A

    International Nuclear Information System (INIS)

    Lerman, Ilya; Chen, Yona; Xing, Baoshan; Chefetz, Benny

    2013-01-01

    Carbon nanotubes, organic contaminants and dissolved organic matter (DOM) are co-introduced into the environment. Thus, the interactions between these components have to be evaluated to better understand their environmental behavior. In this study, single-walled carbon nanotubes (SWCNTs) were used as sorbent, carbamazepine was the primary adsorbate, and bisphenol A and phenanthrene were used as competitors. Strong competition with bisphenol A and no effect of phenanthrene on adsorption of carbamazepine was obtained. The hydrophobic neutral fraction of the DOM exhibited the strongest reductive effect on carbamazepine adsorption, most probably due to interactions in solution. In contrast, the hydrophobic acid fraction decreased carbamazepine adsorption mainly via direct competition. When DOM and bisphenol A were co-introduced, the adsorption of carbamazepine was significantly reduced. This study suggests that the chemical nature of DOM can significantly affect the sorptive behavior of polar organic pollutants with carbon nanotubes when all are introduced to the aquatic system. Highlights: •Bisphenol A is an efficient competitor for carbamazepine. •Phenanthrene does not compete with carbamazepine. •DOM exhibited strong reductive effect on carbamazepine adsorption by SWCNTs. •HoN fraction decreased carbamazepine adsorption due to interactions in solution. •HoA fraction decreased carbamazepine adsorption via direct competition. -- In multi-component system including the main adsorbate and competitor, DOM exhibited significant effect on adsorption of contaminants by carbon nanotubes

  3. Non-recurrence of carbamazepine induced vitiligo after rechallenge with carbamazepine.

    Directory of Open Access Journals (Sweden)

    Masoomeh Saeedloo

    2013-12-01

    Full Text Available Vitiligo is a rare side effect of carbamazepine whose exact mechanism is unknown. The aim of this report is to describe a single case of vitiligo induced by carbamazepine.The case was a patient with Bipolar I disorder whose medications were changed from valproate to carbamazepine and who developed vitiligo after a short while. We followed the case for about four years when he was rechallenged with carbamazepine.When depigmentation occurred, we immediately discontinued carbamazepine after which the depigmented areas improved gradually. About three years later, he received carbamazepine again, but depigmentation did not recur.Carbamazepine-induced vitiligo is not an absolute contraindication for the prescription of carbamazepine if other choices fail to respond or are not tolerated. The case has implications for the mechanism of medication induced vitiligo.

  4. Embryonation of Ostertagia ostertagi eggs affects the outcome of real-time quantitative PCR

    DEFF Research Database (Denmark)

    Drag, Markus; Höglund, Johan; Nejsum, Peter

    prior to detection and quantification by real-time quantitative polymerase chain reaction (qPCR). Fresh O. ostertagi eggs were isolated from cattle faeces and stored at 4°C or 25°C under aerobic or anaerobic conditions. Embryonation was monitored by microscopy and the ITS2 copies were determined by q...... the outcome of qPCR analysis for the quantitative determination of O. ostertagi eggs in cattle faeces. Cold storage at 4°C for up to 3 days or anaerobicvacuum packing at 25°C for up to 336 h will entail no undesirable effects on ITS2 copies....

  5. Embryonation of Ostertagia ostertagi eggs affects the outcome of real-time quantitative PCR

    DEFF Research Database (Denmark)

    Drag, Markus; Höglund, Johan; Nejsum, Peter

    prior to detection and quantification by real-time quantitative polymerase chain reaction (qPCR) . Fresh O. ostertagi eggs were isolated from cattle faeces and stored at 4°C or 25°C under aerobic or anaerobic conditions. Embryonation was monitored by microscopy and the ITS2 copies were determined by q...... the outcome of qPCR analysis for the quantitative determination of O. ostertagi eggs in cattle faeces. Cold storage at 4°C for up to 3 days or anaerobic vacuum packing at 25°C for up to 336 h will entail no undesirable effects on ITS2 copies....

  6. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1–60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  7. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.

    2009-01-01

    Background Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. Objectives To compare efficacy and tolerability of carbamazepine and oxcarbazepine

  8. Derivation of NEM2 affected human embryonic stem cell line Genea079

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea079 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 86% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 98% SSEA4 and gave a PluriTest Pluripotency score of 30.25, Novelty of 1.21. The cell line was negative for Mycoplasma and visible contamination.

  9. A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012.

    Science.gov (United States)

    Tolou-Ghamari, Zahra; Zare, Mohammad; Habibabadi, Jafar Mehvari; Najafi, Mohammad Reza

    2013-03-01

    Carbamazepine has been used as AEDs since 1965, and is most effective against partial seizures. Two basic mechanisms of action have been proposed: 1) enhancement of sodium channel inactivation by reducing high-frequency repetitive firing of action potentials, 2) and action on synaptic transmission. The aim of this study was to provide a review of carbamazepine pharmacokinetics and its management guidelines in Iranian epileptic population. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO), Web of Science were searched; 1600, 722 and 167 research and review articles relevant to the topics; carbamazepine pharmacokinetics, carbamazepine pharmacokinetics in epilepsy and review on carbamazepine pharmacokinetics in epilepsy were found, respectively. Carbamazepine is highly bound to plasma proteins. In patients the protein-bound fraction ranged from 75-80% of the total plasma concentration. Bioavailability ranges from 75-85%. The rate or extent of absorption was not be affected by food. It is completely metabolized and the main metabolite is carbamazepine-epoxide (CBZ-E). Carbamazepine induces its own metabolism, leading to increased clearance, shortened serum half-life, and progressive decrease in serum levels. Increases in daily dosage are necessary to maintain plasma concentration. Severe liver dysfunction may cause disordered pharmacokinetics. In cardiac failure, congestion of major vital organs, including kidneys, may result in abnormally slow absorption and metabolism. Carbamazepine shows variability due to its narrow therapeutic window. Therefore clinical management in a3n Iranian epileptic population should focus on results derived from therapeutic drug monitoring in order to reduce inter and intra- individual variability in plasma drug concentrations.

  10. A Low Ethanol Dose Affects all Types of Cells in Mixed Long-Term Embryonic Cultures of the Cerebellum

    DEFF Research Database (Denmark)

    Pickering, Chris; Wicher, Grzegorz; Rosendahl, Sofi

    2010-01-01

    of this ethanol dose, cultures were exposed for 30 days. After this period, virtually no neurons or myelinating oligodendrocytes were present in the ethanol-treated cultures. In conclusion, chronic exposure to ethanol, even at small doses, dramatically and persistently affects normal development........ We exposed a primary culture of rat cerebellum from embryonic day 17 (corresponding to second trimester in humans) to ethanol at a concentration of 17.6 mM which is roughly equivalent to one glass of wine. Acutely, there was no change in cell viability after 5 or 8 days of exposure relative...... to control. By 11 days, a reduction in the number of viable cells was observed without an accompanying change in caspase-3 activity (marker of apoptotic cell death), suggesting changes in cell proliferation. As the proportion of nestin-positive cells was higher in the ethanol-treated cultures after 5 days...

  11. Characterization of Carbamazepine-Loaded Solid Lipid ...

    African Journals Online (AJOL)

    loaded solid lipid nanoparticles by RESS as well as their characterization has been achieved in this study. Keywords: Rapid expansion of supercritical fluid, Stearic acid, Solid lipid nanoparticles, Carbamazepine, Co-precipitation ...

  12. Carbamazepine - hematologic effects of the use

    Directory of Open Access Journals (Sweden)

    Kamil Leis

    2018-06-01

    Full Text Available Carbamazepine is an antiepileptic drug which exhibits a number of side effects, namely including a headache, abdominal pain, increased blood pressure, but also hematologic disorders. Thrombocytopenia, hypogammaglobulinemia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, pure red cell aplasia, leukemia or eosinophilia with DRESS syndrome belong to the latter. There is a low incidence of carbamazepine pharmacotherapy related symptoms and their exact mechanisms of action are still unknown.

  13. Affect of Bioglass {sup trademark} repeat dosage on mineralisation of embryonic bone 'in vitro'

    Energy Technology Data Exchange (ETDEWEB)

    Maroothynaden, J. [Imperial Coll. of Medicine, London (United Kingdom). Microgravity Tissue Engineering Lab.; Hench, L.L. [Imperial Coll. of Science, Technology and Medicine, London (United Kingdom). Dept. of Materials

    2001-07-01

    Utilising 45S5 Bioglass {sup trademark} extracts, as described previously, 16-day gestation embryonic mouse long-bones were cultured for 4-days while exposed to the same Bioglass{sup circledR} soluble extract solution for two different exposure times. In the first culture, all embryonic femurs were exposed to fresh 45S5 Bioglass {sup trademark} extract every 98 hours. In the second, the long-bones were exposed to fresh 45S5 Bioglass {sup trademark} extract solution every 48 hours. A simultaneous control culture was performed. All embryonic long-bone cultures mineralised after 4-days culture. Increasing the frequency of 45S5 Bioglass {sup trademark} exposure, from one exposure every 96 hrs to fresh exposures every 48 hrs, significantly increased the length and mineral content of the embryonic long-bones. (orig.)

  14. Fate of Carbamazepine during Water Treatment

    DEFF Research Database (Denmark)

    Kosjek, T.; Andersen, Henrik Rasmus; Kompare, Boris

    2009-01-01

    of acridone, hydroxy-(9H,10H)-acridine-9-carbaldehyde, acridone-N-carbaldehyde, and 1-(2-benzaldehyde)-(1H,3H-quinazoline-2,4-dione, while biological breakdown of acridine yielded acridone. In parallel, the transformation product iminostilbene was observed during sample analysis. In addition,this study...... compared the treatment technologies according to the removal of carbamazepine and the production and decay of its transformation products. The most successful method for the removal of carbamazepine was UV treatment, while acridine and acridone were more susceptible to biological treatment. Therefore...

  15. Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

    Science.gov (United States)

    Mixcoatl-Zecuatl, Teresa; Quinonez-Bastidas, Geovanna N; Caram-Salas, Nadia L; Ambriz-Tututi, Monica; Araiza-Saldana, Claudia I; Rocha-Gonzalez, Hector I; Medina-Santillan, Roberto; Reyes-Garcia, Gerardo; Granados-Soto, Vinicio

    2008-01-01

    Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

  16. Stevens-Johnson Syndrome Induced by Carbamazepine Treatment in a Patient Who Previously Had Carbamazepine Induced Pruritus - A Case Report -

    OpenAIRE

    Bae, Hyun Min; Park, Yoo Jung; Kim, Young Hoon; Moon, Dong Eon

    2013-01-01

    Stevens-Johnson syndrome (SJS) is a rare but life-threatening skin reaction disease and carbamazepine is one of its most common causes. We report a case of SJS secondary to carbamazepine in a patient with previous pruritus due to carbamazepine which was given for treatment of trigeminal neuralgia. We would like to caution all providers that carbamazepine readministration should be avoided in the patient with a previous history of SJS or adverse skin reaction. In addition, we strongly recommen...

  17. Carbamazepine overdose after exposure to simethicone: a case report

    Directory of Open Access Journals (Sweden)

    Guneysel Ozlem

    2008-07-01

    Full Text Available Abstract Introduction Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine. Case presentation We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twice daily, and experienced carbamazepine overdose after exposure to simethicone. After cessation of simethicone therapy normal drug levels of carbamazepine were obtained again with the standard dose of the drug. The mechanism of interaction is unknown but the risk of overdose should be considered when prescribing simethicone to a patient who is using carbamazepine. Conclusion Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.

  18. Carbamazepine degradation by gamma irradiation coupled to biological treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shizong [Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084 (China); Wang, Jianlong, E-mail: wangjl@tsinghua.edu.cn [Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory of Radioactive Wastes Treatment, Tsinghua University, Beijing 100084 (China)

    2017-01-05

    Highlights: • Carbamazepine was removed by the combined gamma radiation and biodegradation. • The removal efficiency of carbamazepine increased with dose. • Irradiation could enhance the mineralization of carbamazepine significantly. • The combined irradiation and biodegradation was effective for carbamazepine removal. - Abstract: Carbamazepine is an emerging contaminant and resistant to biodegradation, which cannot be effectively removed by the conventional biological wastewater treatment processes. In this study, the combined gamma irradiation and biodegradation was employed to remove carbamazepine from wastewater. The effect of dose on the removal of carbamazepine was studied at different doses (300, 600 and 800 Gy). The results showed that the removal efficiency of carbamazepine increased with dose increasing during the irradiation process. The maximum removal efficiency was 99.8% at 800 Gy, while the removal efficiency of total organic carbon (TOC) was only 26.5%. The removal efficiency of TOC increased to 79.3% after the sequent biological treatment. In addition, several intermediates and organic acids were detected. The possible degradation pathway of carbamazepine during the integrated irradiation and biodegradation was proposed. Based on the overall analysis, the combined gamma irradiation and biological treatment process can be an alternative for removing the recalcitrant organic pollutants such as carbamazepine from wastewater.

  19. Eighteen-Year Cryopreservation Does Not Negatively Affect the Pluripotency of Human Embryos: Evidence from Embryonic Stem Cell Derivation

    Science.gov (United States)

    Rungsiwiwut, Ruttachuk; Numchaisrika, Pranee; Ahnonkitpanit, Vichuda; Isarasena, Nipan; Virutamasen, Pramuan

    2012-01-01

    Abstract Human embryonic stem (hES) cells are considered to be a potential source for the therapy of human diseases, drug screening, and the study of developmental biology. In the present study, we successfully derived hES cell lines from blastocysts developed from frozen and fresh embryos. Seventeen- to eighteen-year-old frozen embryos were thawed, cultured to the blastocyst stage, and induced to form hES cells using human foreskin fibroblasts. The Chula2.hES cell line and the Chula4.hES and Chula5.hES cell lines were derived from blastocysts developed from frozen and fresh embryos, respectively. The cell lines expressed pluripotent markers, including alkaline phosphatase (AP), Oct3/4, stage-specific embryonic antigen (SSEA)-4, and tumor recognition antigen (TRA)-1-60 and TRA-1-81 as detected with immunocytochemistry. The real-time polymerase chain reaction (RT-PCR) results showed that the cell lines expressed pluripotent genes, including OCT3/4, SOX2, NANOG, UTF, LIN28, REX1, NODAL, and E-Cadherin. In addition, the telomerase activities of the cell lines were higher than in the fibroblast cells. Moreover, the cell lines differentiated into all three germ layers both in vitro and in vivo. The cell lines had distinct identities, as revealed with DNA fingerprinting, and maintained their normal karyotype after a long-term culture. This study is the first to report the successful derivation of hES cell lines in Thailand and that frozen embryos maintained their pluripotency similar to fresh embryos, as shown by the success of hES cell derivation, even after years of cryopreservation. Therefore, embryos from prolonged cryopreservation could be an alternative source for embryonic stem cell research. PMID:23514952

  20. Sorption and desorption of carbamazepine from water by smectite clays.

    Science.gov (United States)

    Zhang, Weihao; Ding, Yunjie; Boyd, Stephen A; Teppen, Brian J; Li, Hui

    2010-11-01

    Carbamazepine is a prescription anticonvulsant and mood stabilizing pharmaceutical administered to humans. Carbamazepine is persistent in the environment and frequently detected in water systems. In this study, sorption and desorption of carbamazepine from water was measured for smectite clays with the surface negative charges compensated with K+, Ca2+, NH4+, tetramethylammonium (TMA), trimethylphenylammonium (TMPA) and hexadecyltrimethylammonium (HDTMA) cations. The magnitude of sorption followed the order: TMPA-smectite≥HDTMA-smectite>NH4-smectite>K-smectite>Ca-smectite⩾TMA-smectite. The greatest sorption of carbamazepine by TMPA-smectite is attributed to the interaction of conjugate aromatic moiety in carbamazepine with the phenyl ring in TMPA through π-π interaction. Partitioning process is the primary mechanism for carbamazepine uptake by HDTMA-smectite. For NH4-smectite the urea moiety in carbamazepine interacts with exchanged cation NH4+ by H-bonding hence demonstrating relatively higher adsorption. Sorption by K-, Ca- and TMA-smectites from water occurs on aluminosilicate mineral surfaces. These results implicate that carbamazepine sorption by soils occurs primarily in soil organic matter, and soil mineral fractions play a secondary role. Desorption of carbamazepine from the sorbents manifested an apparent hysteresis. Increasing irreversibility of desorption vs. sorption was observed for K-, Ca-, TMA-, TMPA- and HDTMA-clays as aqueous carbamazepine concentrations increased. Desorption hysteresis of carbamazepine from K-, Ca-, NH4-smectites was greater than that from TMPA- and HDTMA-clays, suggesting that the sequestrated carbamazepine molecules in smectite interlayers are more resistant to desorption compared to those sorbed by organic phases in smectite clays. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response.

    Directory of Open Access Journals (Sweden)

    Anirban Chakraborty

    Full Text Available Ribosome is responsible for protein synthesis in all organisms and ribosomal proteins (RPs play important roles in the formation of a functional ribosome. L11 was recently shown to regulate p53 activity through a direct binding with MDM2 and abrogating the MDM2-induced p53 degradation in response to ribosomal stress. However, the studies were performed in cell lines and the significance of this tumor suppressor function of L11 has yet to be explored in animal models. To investigate the effects of the deletion of L11 and its physiological relevance to p53 activity, we knocked down the rpl11 gene in zebrafish and analyzed the p53 response. Contrary to the cell line-based results, our data indicate that an L11 deficiency in a model organism activates the p53 pathway. The L11-deficient embryos (morphants displayed developmental abnormalities primarily in the brain, leading to embryonic lethality within 6-7 days post fertilization. Extensive apoptosis was observed in the head region of the morphants, thus correlating the morphological defects with apparent cell death. A decrease in total abundance of genes involved in neural patterning of the brain was observed in the morphants, suggesting a reduction in neural progenitor cells. Upregulation of the genes involved in the p53 pathway were observed in the morphants. Simultaneous knockdown of the p53 gene rescued the developmental defects and apoptosis in the morphants. These results suggest that ribosomal dysfunction due to the loss of L11 activates a p53-dependent checkpoint response to prevent improper embryonic development.

  2. A comparison of carbamazepine Divitabs and a normal carbamazepine preparation in psychiatric and oligophrenic patients

    NARCIS (Netherlands)

    Nijdam, J.R.; Doorschot, C.H.; Van Bavel, L.P.; Loonen, A.J.M.

    1992-01-01

    Twenty patients who had become accustomed to a stable oral carbamazepine dose participated in an open, randomized, two-centre, cross-over study, in which ordinary tablets and Divitabs (a new sustained release preparation) were compared. Pharmacokinetic parameters, seizure control, effects on the

  3. Studies on improving ostrich egg hatch ability and its relation with some factors affecting embryonic development during artificial incubation

    International Nuclear Information System (INIS)

    Amer, N.S.I.

    2012-01-01

    The present study was carried out in co-operation between the Ostrich Production Farm, Nuclear Research Center, Atomic Energy Authority, Cairo, Egypt and the Faculty of Agriculture, AL-Azhar University, Nasr City, Cairo, Egypt. Ostrich eggs were obtained from Resk Company for Ostrich Production and set for incubation at ElShfie Farm, Belbas, Sharkia, Egypt. The objectives are:1- To follow up changes in some vital physiological parameters and blood components associated with ostrich embryonic development during incubation and to provide reference blood biochemical baseline values for future studies of avian species and to document novel information on some normal changes associated with growth of the developing ostrich embryo during the incubation, as no similar and complete data could be found on this aspect in the literature. 2- In an effort to improve the hatch ability and hatching performance of ostrich eggs by testing the effect of in ovo injection of several nutrients. Two trials were carried out: 1-First trial To follow up changes in some vital physiological parameters and blood components associated with ostrich embryonic development during incubation. A total number of 60 ostrich eggs weighed between 1300 and 1500 g were obtained from from Resk Company for Ostrich Production. Eggs were collected weekly in patches of 25 eggs and Egg incubation was performed in ElShfie Farm, Belbas, Egypt. Egg weight and egg weight loss during incubation were determined on each eggs.2- Second Trial In vivo injection In an effort to improve the hatch ability and hatching performance of ostrich eggs by testing the effect of in ovo injection of several nutrients. A total of 100 fertile ostrich eggs weighed between 1300 and 1500 g were obtained from from Resk Company for Ostrich Production. Eggs were collected weekly in patches of 25 eggs and egg incubation was performed in ElShfie Farm, Belbas, Egypt. Eggs were injected at the 7 th day of incubation to deposit test material in

  4. Hippocampal agenesis in an individual who engaged in violent criminal behaviors after discontinuing carbamazepine and paroxetine treatment.

    Science.gov (United States)

    Hanada, Hiroaki; Akiyoshi, Jotaro; Kanehisa, Masayuki; Ishitobi, Yoshinobu; Tsuru, Jusen; Tanaka, Yoshihiro; Shimomura, Tsuyoshi; Kawano, Yoshihisa

    2013-01-01

    Antidepressant discontinuation syndrome (ADS) occurs after abrupt discontinuation of an antidepressant medication. A 23-year-old man with right hippocampal agenesis demonstrated sexual crime (hypersexuality) since the age of eight and had been successfully treated with carbamazepine since the age of 13. He had required increased doses of paroxetine and carbamazepine owing to the development of an unstable affect after quitting his job. He abruptly stopped taking his medication for 3 days and his criminal behaviors re-emerged. We examined changes in brain structure and activity before and after medication cessation, using MRI and functional MRI (fMRI). The image of a girl in a swimsuit increased activity in the thalamus only after medication discontinuation. The alteration in thalamic activity might induce hypersexuality. We conclude that a primary hypersexuality had been suppressed with carbamazepine and paroxetine treatment, and the discontinuation of the medication caused the hypersexuality. © 2012 American Academy of Forensic Sciences.

  5. High levels of maternally transferred mercury do not affect reproductive output or embryonic survival of northern watersnakes (Nerodia sipedon).

    Science.gov (United States)

    Chin, Stephanie Y; Willson, John D; Cristol, Daniel A; Drewett, David V V; Hopkins, William A

    2013-03-01

    Maternal transfer is an important exposure pathway for contaminants because it can directly influence offspring development. Few studies have examined maternal transfer of contaminants, such as mercury (Hg), in snakes, despite their abundance and high trophic position in many ecosystems where Hg is prevalent. The objectives of the present study were to determine if Hg is maternally transferred in northern watersnakes (Nerodia sipedon) and to evaluate the effects of maternal Hg on reproduction. The authors captured gravid female watersnakes (n = 31) along the South River in Waynesboro, Virginia, USA, where an extensive Hg-contamination gradient exists. The authors measured maternal tissue and litter Hg concentrations and, following birth, assessed (1) reproductive parameters (i.e., litter size and mass, neonate mass); (2) rates of infertility, death during development, stillbirths, malformations, and runts; and (3) the overall viability of offspring. Mercury concentrations in females were strongly and positively correlated with concentrations in litters, suggesting that N. sipedon maternally transfer Hg in proportion to their tissue residues. Maternal transfer resulted in high concentrations (up to 10.10 mg/kg dry wt total Hg) of Hg in offspring. The authors found little evidence of adverse effects of Hg on these measures of reproductive output and embryonic survival, suggesting that N. sipedon may be more tolerant of Hg than other vertebrate species. Given that this is the first study to examine the effects of maternally transferred contaminants in snakes and that the authors did not measure all reproductive endpoints, further research is needed to better understand factors that influence maternal transfer and associated sublethal effects on offspring. Copyright © 2013 SETAC.

  6. Replacing carbamazepine slow-release tablets with carbamazepine suppositories: a pharmacokinetic and clinical study in children with epilepsy.

    Science.gov (United States)

    Arvidsson, J; Nilsson, H L; Sandstedt, P; Steinwall, G; Tonnby, B; Flesch, G

    1995-03-01

    A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration.

  7. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain. Sinan Mohammed Abdullah AL-Mahmood, Shahrin Tarmizi Bin Che Abdullah, Nik Nur Fatnoon Nik Ahmad, Abdul Hadi Bin Mohamed, Tariq Abdul Razak ...

  8. Carbamazepine induces mitotic arrest in mammalian Vero cells

    International Nuclear Information System (INIS)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V.; Hazen, M.J.

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells

  9. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Hazen, M.J. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)], E-mail: mariajose.hazen@uam.es

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells.

  10. Simultaneous Quantification of Three Polymorphic Forms of Carbamazepine in the Presence of Excipients Using Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Marco Farias

    2014-09-01

    Full Text Available The occurrence of polymorphic transitions is a serious problem for pharmaceutical companies, because it can affect the bioavailability of the final product. With several known polymorphic forms carbamazepine is one of the most problematic drugs in this respect. Raman spectroscopy is a vibrational technique that is becoming very important in the pharmaceutical field, mainly due to its highly specific molecular fingerprint capabilities and easy use as a process analytical tool. However, multivariate methods are necessary both for identification and quantification. In this work an analytical methodology using Raman spectroscopy and interval Partial Least Squares Regression (iPLS, was developed in order to quantify mixtures of carbamazepine polymorphs in the presence of the most common excipients. The three polymorphs CBZ I, CBZ III and CBZ DH (which is a dihydrate were synthesized and characterized by PXRD and DSC. Subsequently, tablets were manufactured using excipients and 15 different mixtures of carbamazepine polymorphs. The iPLS model presented average prediction validation errors of 1.58%, 1.04% and 0.22% wt/wt, for CBZ I, CBZ III and CBZ DH, respectively, considering the whole mass of the tablet. The model presents a good prediction capacity and the proposed methodology could be used to perform quality control in final products.

  11. Molecular toxicity of triclosan and carbamazepine to green algae Chlorococcum sp.: A single cell view using synchrotron-based Fourier transform infrared spectromicroscopy.

    Science.gov (United States)

    Xin, Xiaying; Huang, Guohe; Liu, Xia; An, Chunjiang; Yao, Yao; Weger, Harold; Zhang, Peng; Chen, Xiujuan

    2017-07-01

    Although pharmaceuticals and personal care products have been used and introduced into the environment in large quantities, little information on potential ecological risks is currently available considering their effects on living organisms. We verified the feasibility of using synchrotron-based Fourier Transform Infrared (SR-FTIR) spectromicroscopy to explore in vivo toxic effects on single living Chlorococcum sp. cells. The study provided important information to achieve a better understanding of the toxic mechanism of triclosan and carbamazepine on living algae Chlorococcum sp.. Triclosan and carbamazepine had distinctive toxic effects on unicellular living algae. Most strikingly, triclosan had more dramatic toxic effects on biochemical components than carbamazepine. Triclosan can affect algae primarily by inhibiting fatty acid synthesis and causing protein aggregation. The toxicity response was irreversible at higher concentration (100.000 μM), but attenuated at lower concentration (0.391 μM) as time extended. Carbamazepine can produce hydrophobic interactions to affect the phospholipid bilayer and work on specific proteins to disfunction the cell membrane. Carbamazepine-exposed cells developed a resistance while extending exposure time. This is the first demonstration from an ecological standpoint that SR-FTIR can provide an innovative approach to reveal the toxicity of emerging pollutants in aquatic environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study

    DEFF Research Database (Denmark)

    Jentink, Janneke; Dolk, Helen; Loane, Maria A

    2010-01-01

    To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy.......To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy....

  13. Impairment of the in vitro Release of Carbamazepine from Tablets

    Directory of Open Access Journals (Sweden)

    Alija Uzunović

    2010-08-01

    Full Text Available Carbamazepine belongs to the class II biopharmaceutical classification system (BCS which is characterized by a high per-oral dose, a low aqueous solubility and a high membrane permeability. The bioavailability of such a drug is limited by the dissolution rate. The present study deals with the formulations of immediate release tablets of poorly soluble carbamazepine. As model tablets for this investigation, two formulations (named “A” and “B” formulations of carbamazepine tablets labeled to contain 200 mg were evaluated. The aim of this study was to establish possible differences in dissolution profile of these two formulations purchased from the local market.The increased crystallinity together with enlarged particle size, enhanced aggregation and decreased wettability of the drug, resulted in insufficient dissolution rate for formulation “B’.’ From the dissolution point of view, this formulation was inferior to the formulation “A, due to the solubilization effect.

  14. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures.

    Science.gov (United States)

    Koch, Marcus W; Polman, Susanne Kl

    2009-10-07

    Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. To compare efficacy and tolerability of carbamazepine and oxcarbazepine monotherapy for partial onset seizures. We searched the Cochrane Epilepsy Group Specialised Register (4 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 3, 2009), MEDLINE (January 1966 to May 2008), reference lists of relevant articles and conference proceedings. We also contacted manufacturers and researchers in the field for published or unpublished data. Blinded and unblinded randomised controlled trials of carbamazepine versus oxcarbazepine monotherapy for partial onset seizures. Both authors independently assessed trial quality, according to the guidelines in the Cochrane Reviewer's Handbook, and extracted information about study population, type of intervention, outcome measures and study design. All analyses in this review are by intention-to-treat. We tested for statistical heterogeneity among the identified studies using the chi-squared test. Three trials (723 participants) were included. Only one trial used adequate outcome measures of efficacy; therefore, the results pertaining to efficacy are based on a single trial, whereas the results pertaining to adverse events are based on all three included trials. There was no overall difference in time to treatment withdrawal between the two drugs (hazard ratio (HR) of oxcarbazepine (OXC) versus carbamazepine (CBZ): 1.04, 95% confidence interval (CI) 0.78 to 1.39). Further analyses showed no significant difference in treatment withdrawal for unacceptable side effects (HR of OXC versus CBZ: 0.85, 95% CI 0.59 to 1.24) and in treatment withdrawal for inadequate seizure control (HR of OXC versus CBZ: 1.33, 95% CI 0.82 to 2.15). Oxcarbazepine and carbamazepine appeared to be similarly effective

  15. Efficiency of haplotype-based methods to fine-map QTLs and embryonic lethals variants affecting fertility: illustration with a deletion segregating in Nordic Red cattle Corresponding

    DEFF Research Database (Denmark)

    Kadri, Naveen Kumar; Sahana, Goutam; Guldbrandtsen, Bernt

    2014-01-01

    Despite its importance, fertility has been declining in many cattle populations. In dairy cattle, this decline is often attributed to the negative correlation between fertility and productions traits. Recent studies showed that embryonic lethal variants might also account for a non-negligible fra...

  16. Influence of carbamazepin and diclofenac on the radio-T3/T4-distribution and the maximal binding capacity of thyroid hormone binding proteins

    International Nuclear Information System (INIS)

    Sternad, H.; Albrecher, B.; Langsteger, W.; Eber, O.

    1993-01-01

    Marked changes in plasma thyroid function parameters due to medication have been described in literature. We, therefore, studied the influence of routine administration of carbamazepine and diclofenac upon the radio T3/T4 distribution to specific thyroid transport proteins as well as their maximal binding capacity (MBC) for T4. Both drugs have been found to lead to changes in T3 and T4 distribution but not to any influence upon MBC. The parameters of thyroid function mostly revealed reduced FT3 and FT4 values while bTSH was affected only by carbamazepine administration. (authors)

  17. Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

    Directory of Open Access Journals (Sweden)

    Jasmina Tonic – Ribarska

    2012-03-01

    Full Text Available Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

  18. Neuroleptic Malignant Syndrome Caused by a Combination of Carbamazepine and Amitriptyline

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2012-01-01

    Full Text Available A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.

  19. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    GBP and CBZ, which may be applied in the treatment of pain in diabetic neuropathy. Keywords: Diabetic neuropathy, Carbamazepine, .... manifested at two levels: the peripheral and central levels. On the peripheral level, there is an ... It is an antiepileptic drug with a structure similar to GABA, which is a neurotransmitter that.

  20. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

    NARCIS (Netherlands)

    Berghuis, Bianca; van der Palen, Job; de Haan, Gerrit-Jan; Lindhout, Dick; Koeleman, Bobby P.C.; Sander, Josemir W.; Møller, Rikke S.; Nikanorova, Marina; Ingason, Andrés; Depondt, Chantal; Johnson, Michael R.; Langley, Sarah R; Klein, Karl Martin; McCormack, Mark; Delanty, Norman; Cavalleri, Gianpiero L.; van Zijl, Janic; Muhle, Hiltrud; Borghei, Mojgansadat; Donatello, Simona; Willis, Joseph; Leu, Costin; Heggeli, Kristin; Avbersek, Andreja; Sisodiya, Sanjay M.; Gamberdella, Antonio; Weckhuysen, Sarah; Kunz, Wolfram S.; Striano, Pasquale; Zara, Federico; Brodie, Martin J.; Stefánsson, Kári; Marson, Anthony G.; Jorgensen, Andrea; Auce, Pauls; Francis, Ben; Srivastava, Prashant; Sills, Graeme J.; Primec, Zvonka Rener; Krause, Roland; Wolking, Stefan; Weber, Yvonne G.; Rau, Sarah; Hengsbach, Christian; Lerche, Holger; Sonsma, Anja; Krenn, Martin; Zimprich, Fritz; Pataraia, Ekaterina

    2017-01-01

    Objective: To ascertain possible determinants of carbamazepine (CBZ)– and oxcarbazepine (OXC)–induced hyponatremia in a large cohort of people with epilepsy. Methods: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment

  1. Lichenoid reaction to carbamazepine in the oral mucosa: case report.

    Science.gov (United States)

    Artico, Gabriela; Bruno, Ingrid S; Seo, Juliana; Hirota, Silvio K; Acay, Renata; Migliari, Dante A

    2011-01-01

    Lichenoid drug reactions are more common in skin, but they may also occur in the oral mucosa. It is difficult to diagnose these lesions due to their clinical similarity to the idiopathic oral lichen planus lesions. The present article reports a case of lichenoid reaction in oral mucosa associated to the use of carbamazepine, emphasizing the diagnostic process.

  2. The effects of carbamazepine on thyroid functions in childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Mehmet İbrahim Turan

    2013-12-01

    Full Text Available Objective: To investigate the effects of carbamazepinetherapy on thyroid function tests in childrenMethods: The carbamazepine group consisted of 58 childrenunder observation for epilepsy, and the control groupof 54 healthy children. Age of onset, length of drug use,drug dosage and laboratory parameters including free triiodothyronine(FT3, free thyroxin (FT4 and thyrotropin(TSH were recorded. These data were then comparedagainst those from the control group.Results: In the carbamazepine group, FT3 was 3.86 ±0.43 pg/mL, FT4 was 1.15 ± 0.18 mg/dL and TSH: 2.58 ±1.33 ml U/L. In the control group, FT3 was 4.13 ± 0.59 pg/mL, FT4 1.34 ± 0.13 mg/dL and TSH was 2.06 ± 0.89 mlU/L. No statistically significant difference between rates ofsubclinical hypothyroidism was determined between thetwo groups (p=0.196.Conclusion: Although, carbamazepine reduces thyroidhormone concentrations, rarely causes hypothyroidism.Key words: Child, carbamazepine, thyroid function tests

  3. Pure red-cell aplasia associated with carbamazepine

    African Journals Online (AJOL)

    1990-08-18

    Aug 18, 1990 ... phenobarbitone and clonazepam without success. On 1. February 1988 medication was changed to carbamazepine (50 mg in the morning and 100 mg at night), which controlled the seizures satisfactorily. She received no other drugs. A full blood count done on 23 March 1988 was within normal limits.

  4. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

    DEFF Research Database (Denmark)

    Berghuis, Bianca; van der Palen, Job; de Haan, Gerrit-Jan

    2017-01-01

    OBJECTIVE: To ascertain possible determinants of carbamazepine (CBZ)- and oxcarbazepine (OXC)-induced hyponatremia in a large cohort of people with epilepsy. METHODS: We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment...

  5. Exfoliative Dermatitis Due To Carbamazepine In An Epileptic Patient

    Directory of Open Access Journals (Sweden)

    Ghosh Sadhan Kr

    1995-01-01

    Full Text Available A young epileptic girl of 17 years who was being treated with carbamazepine suddenly developed exanthematous skin eruption all over the body resulting in exfoliative dermatitis within 2 days of onset. The drug was withdrawn and the patient responded well with symptomatic treatment.

  6. Comparative evaluation of carbamazepine release from single and ...

    African Journals Online (AJOL)

    In the present study the release rate and kinetics of carbamazepine as a model drug from various single and bi-polymeric matrices were studied. Matrices containing different percentages of hydroxylpropyl methylcellulose (HPMC), ethylcellulose (EC), Eudragit RS (EuRS) or various ratios of polymer blends based on HPMC ...

  7. Ecotoxicity of carbamazepine and its UV photolysis transformation products

    DEFF Research Database (Denmark)

    Donner, E.; Kosjek, T.; Qualmann, Signe

    2013-01-01

    the treatment period, together with concurrent increases in acridine and acridone concentrations. Ecotoxicity was shown to increase in parallel with carbamazepine degradation indicating that the mixture of degradation products formed was more toxic than the parent compound, and all three ecotoxicity endpoints...

  8. Vitamin B6 and homocysteine levels in carbamazepine treated ...

    African Journals Online (AJOL)

    Objectives: The study focused on the plasma levels of vitamin B6 and homocysteine in ... ed with carbamazepine were selected at out-patient De- .... Patients' demographic data and types of seizures are ex- .... morphisms that may alter the individual response to a .... genotype, homocysteine, and stroke risk: a meta-analy-.

  9. Carbamazepine in the treatment of Lyme disease-induced hyperacusis.

    Science.gov (United States)

    Nields, J A; Fallon, B A; Jastreboff, P J

    1999-01-01

    Lyme disease-induced hyperacusis can be an intensely disabling, chronic condition that is accompanied by posttraumatic stress disorder-like psychobehavioral sequelae. The authors describe effective treatment of 2 patients with carbamazepine. Speculations regarding a mode of action are offered.

  10. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    International Nuclear Information System (INIS)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N.

    1999-01-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au)

  11. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N. [Psychiatric Hospital, Dept. of Biological Psychiatry, Risskov (Denmark)

    1999-02-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au) 46 refs.

  12. Composted biosolids and treated wastewater as sources of pharmaceuticals and personal care products for plant uptake: A case study with carbamazepine

    International Nuclear Information System (INIS)

    Ben Mordechay, Evyatar; Tarchitzky, Jorge; Chen, Yona; Shenker, Moshe; Chefetz, Benny

    2018-01-01

    Irrigation with treated wastewater (TWW) and application of biosolids to arable land expose the agro-environment to pharmaceuticals and personal care products (PPCPs) which can be taken up by crops. In this project, we studied the effect of a carrier medium (e.g., biosolids and TWW) on plant (tomato, wheat and lettuce) uptake, translocation and metabolism of carbamazepine as a model for non-ionic PPCPs. Plant uptake and bioconcentration factors were significantly lower in soils amended with biosolids compared to soils irrigated with TWW. In soils amended with biosolids and irrigated with TWW, the bioavailability of carbamazepine for plant uptake was moderately decreased as compared to plants grown in soils irrigated with TWW alone. While TWW acts as a continuous source of PPCPs, biosolids act both as a source and a sink for these compounds. Moreover, it appears that decomposition of the biosolids in the soil after amendment enhances their adsorptive properties, which in turn reduces the bioavailability of PPCPs in the soil environment. In-plant metabolism of carbamazepine was found to be independent of environmental factors, such as soil type, carrier medium, and absolute amount implemented to the soil, but was controlled by the total amount taken up by the plant. - Highlights: • Bioaccumulation of carbamazepine is higher in plants irrigated with TWW than in plants grown in soils applied with biosolids. • Application of composted biosolids reduces the bioavailability of carbamazepine originated from TWW irrigation. • Plant metabolism of carbamazepine is affected by the total amount taken-up by the plant. - Bioavailability of PPCPs originated from biosolids amendment is lower than the bioavailability of those introduced by irrigation with treated wastewater.

  13. Amelioration of erectile dysfunction following a switch from carbamazepine to oxcarbazepine: recent clinical experience.

    Science.gov (United States)

    Sachdeo, Rajesh; Sathyan, Revathi R

    2005-07-01

    Oxcarbazepine is an antiepileptic drug (AED) indicated for use as monotherapy and add-on therapy in adults and children 4 years of age and older. Despite being structurally related to carbamazepine, oxcarbazepine differs substantially in its pharmacokinetic and safety profile; oxcarbazepine has a much lower risk of pharmacokinetic drug-drug interactions than carbamazepine. Carbamazepine has also been shown to induce the hepatic synthesis of sex hormone-binding globulin, thus reducing free serum testosterone levels and possibly causing erectile dysfunction (ED) in some men; these effects have not been observed with oxcarbazepine. This paper provides a discussion of recent clinical experience with men who presented in private clinical practice with complaints of ED while being treated with carbamazepine for seizure disorders. The four illustrative case studies presented in this report suggest that switching AED treatment from carbamazepine to oxcarbazepine in men with epilepsy can reduce the ED side effects observed with carbamazepine.

  14. ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells

    DEFF Research Database (Denmark)

    Riso, Vincenzo; Cammisa, Marco; Kukreja, Harpreet

    2016-01-01

    ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi......-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS...... the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet...

  15. How life history influences the responses of the clam Scrobicularia plana to the combined impacts of carbamazepine and pH decrease

    International Nuclear Information System (INIS)

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J.; Esteves, Valdemar I.; Wrona, Frederick J.; Soares, Amadeu M.V. M.; Figueira, Etelvina

    2015-01-01

    In the present study, the bivalve Scrobicularia plana, collected from two contrasting areas (pristine location and mercury contaminated area), was selected to assess the biochemical alterations imposed by pH decrease, carbamazepine (an antiepileptic) and the combined effect of both stressors. The effects on oxidative stress related biomarkers after 96 h exposure revealed that pH decrease and carbamazepine induced alterations on clams, with greater impacts on individuals from the contaminated area which presented higher mortality, higher lipid peroxidation and higher glutathione S-transferase activity. These results emphasize the risk of extrapolating results from one area to another, since the same species inhabiting different areas may be affected differently when exposed to the same stressors. Furthermore, the results obtained showed that, when combined, the impact of pH decrease and carbamazepine was lower than each stressor acting alone, which could be related to the defence mechanism of valves closure when bivalves are under higher stressful conditions. - Highlights: • Environmentally relevant concentrations of CBZ and pH 7.1 impacted the performance of Scrobicularia plana. • The combination of CBZ and pH 7.1 did not induce higher impacts compared with stressors acting alone. • Clams from a polluted area showed greater alterations than clams collected from an unpolluted area. - pH decrease and carbamazepine induced biochemical alterations on clams (Scrobicularia plana), with greater impacts on individuals from the contaminated area

  16. Half pitch lower sound perception caused by carbamazepine.

    Science.gov (United States)

    Konno, Shyu; Yamazaki, Etsuko; Kudoh, Masako; Abe, Takashi; Tohgi, Hideo

    2003-09-01

    We report a 16-year-old woman with secondary generalization of partial seizure, who complained of an auditory disturbance after carbamazepine (CBZ) administration. She had been taking sodium valproate (VPA) from the age of 15. However, her seizures remained poorly controlled. We changed her antiepileptic drug from VPA to CBZ. At 1 week after CBZ administration, she noticed that electone musical performances were heard as a semitone lower. When oral administration of CBZ was stopped, her pitch perception returned to normal. If she had not been able to discern absolute pitch, she might have been unable to recognize her lowered pitch perception. Auditory disturbance caused by CBZ is reversible and very rare.

  17. Erythema multiforme as the result of taking carbamazepine

    Directory of Open Access Journals (Sweden)

    Maharani Laillyza Apriasari

    2010-06-01

    Full Text Available Background: Erythema multiforme is an acute mucocutaneus disease which is caused by the hypersensitivity reaction. It is characterized by target lesions on the skin or ulcerative oral lesion. Etiology of the disease is unknown, it is currently considered as immunologic disease. The triggering factors is the use of certain type of drugs like antibiotics, anticonvulsant, and NSAID. Most of the dentists do not know about it is mechanism, so a lot of people consider it as a malpractice. Purpose: This paper reported a case of a man, 46 years old which had ulcerative oral mucous, peeled and pain lips after taking carbamazepine drugs. Case: The clinical diagnosis of this case was erythema multiforme because of the hypersensitivity reaction as the result of taking carbamazepine. Case management: The final diagnosis based on anamnesis history of taking systemic drugs and clinical manifestation of erythema multiforme in the oral cavity. The drugs therapy that had been given were antihistamine, oral corticosteroid, gargle liquid contained of topical anesthetic, corticosteroid, and antibiotic. Conclusion: In this case, it can be concluded that erythema multiforme appeared was triggered by taking carbamazepine as the drug of choice for trigeminal neuralgia therapy. These drugs can cause type III hypersensitivity reaction. The final diagnosis based on anamnesis history of taking carbamazepine before lesions erupted and the characterized clinical manifestation.Latar belakang: Erythema multiforme adalah penyakit mukokutaneus akut yang menyerang kulit dan mukosa sebagai akibat dari reaksi hipersensitivitas. Secara karakteristik ditandai oleh lesi target pada kulit atau lesi ulserasi pada mukosa rongga mulut. Etiologi penyakit ini belum jelas, diduga karena adanya reaksi imunologi. Pencetusnya dikarenakan adanya pemakaian obat-obatan tertentu seperti antibiotik, antikonvulsan dan NSAID. Banyak dokter gigi kurang memahami mekanisme timbulnya penyakit ini, sehingga

  18. Secondary hypogammaglobilinemia after use of carbamazepine: case report and review

    Directory of Open Access Journals (Sweden)

    Castro Ana Paula B Moschione

    2001-01-01

    Full Text Available Immunologic disorders related to anticonvulsant therapy have been described in the last three decades, including cellular and humoral alterations that result in recurrent infections; however, the physiopathologic mechanisms are not completely understood. This report describes a patient with complex partial epilepsy and hypogammaglobulinemia while in treatment with carbamazepine, with significant improvement in clinical signs and laboratory tests after substitution to sodium valproate. The authors stress the importance of clinical and laboratory evaluation of patients in continuous anticonvulsant therapy, including immunoglobulins levels and peripheral blood evaluations.

  19. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2011-03-24

    Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.

  20. Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

    Science.gov (United States)

    Malhotra, S; Dixit, R K; Garg, S K

    2002-01-01

    The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

  1. Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac.

    Science.gov (United States)

    Ferrari, Benoît; Paxéus, Nicklas; Lo Giudice, Roberto; Pollio, Antonino; Garric, Jeanne

    2003-07-01

    In four countries (France, Greece, Italy, and Sweden) occurrence in sewage treatment plant (STP) effluents and ecotoxicity of the pharmaceuticals carbamazepine, clofibric acid, and diclofenac were investigated. Bioassays were performed on bacteria, algae, microcrustaceans, and fishes in order to calculate their predicted no-effect concentrations (PNEC) and to perform a first approach of risk characterization. For this aim, risk has been estimated by the predicted environmental concentration/PNEC ratio and the measured environmental concentration/PNEC ratio. First, regarding the PNEC, carbamazepine appears to be the more hazardous compound. Second, even though it is demonstrated that carbamazepine, clofibric acid, and diclofenac have been detected in effluents, only carbamazepine have been detected in all sewage treatment plants with the greatest concentrations. Third, risk quotients greater than unity were calculated only for carbamazepine, suggesting that risk for the water compartment is expected.

  2. Structure and barrier properties of human embryonic stem cell-derived retinal pigment epithelial cells are affected by extracellular matrix protein coating.

    Science.gov (United States)

    Sorkio, Anni; Hongisto, Heidi; Kaarniranta, Kai; Uusitalo, Hannu; Juuti-Uusitalo, Kati; Skottman, Heli

    2014-02-01

    Extracellular matrix (ECM) interactions play a vital role in cell morphology, migration, proliferation, and differentiation of cells. We investigated the role of ECM proteins on the structure and function of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells during their differentiation and maturation from hESCs into RPE cells in adherent differentiation cultures on several human ECM proteins found in native human Bruch's membrane, namely, collagen I, collagen IV, laminin, fibronectin, and vitronectin, as well as on commercial substrates of xeno-free CELLstart™ and Matrigel™. Cell pigmentation, expression of RPE-specific proteins, fine structure, as well as the production of basal lamina by hESC-RPE on different protein coatings were evaluated after 140 days of differentiation. The integrity of hESC-RPE epithelium and barrier properties on different coatings were investigated by measuring transepithelial resistance. All coatings supported the differentiation of hESC-RPE cells as demonstrated by early onset of cell pigmentation and further maturation to RPE monolayers after enrichment. Mature RPE phenotype was verified by RPE-specific gene and protein expression, correct epithelial polarization, and phagocytic activity. Significant differences were found in the degree of RPE cell pigmentation and tightness of epithelial barrier between different coatings. Further, the thickness of self-assembled basal lamina and secretion of the key ECM proteins found in the basement membrane of the native RPE varied between hESC-RPE cultured on compared protein coatings. In conclusion, this study shows that the cell culture substrate has a major effect on the structure and basal lamina production during the differentiation and maturation of hESC-RPE potentially influencing the success of cell integrations and survival after cell transplantation.

  3. Intracellular ice and cell survival in cryo-exposed embryonic axes of recalcitrant seeds of Acer saccharinum: an ultrastructural study of factors affecting cell and ice structures.

    Science.gov (United States)

    Wesley-Smith, James; Berjak, Patricia; Pammenter, N W; Walters, Christina

    2014-03-01

    Cryopreservation is the only long-term conservation strategy available for germplasm of recalcitrant-seeded species. Efforts to cryopreserve this form of germplasm are hampered by potentially lethal intracellular freezing events; thus, it is important to understand the relationships among cryo-exposure techniques, water content, structure and survival. Undried embryonic axes of Acer saccharinum and those rapidly dried to two different water contents were cooled at three rates and re-warmed at two rates. Ultrastructural observations were carried out on radicle and shoot tips prepared by freeze-fracture and freeze-substitution to assess immediate (i.e. pre-thaw) responses to cooling treatments. Survival of axes was assessed in vitro. Intracellular ice formation was not necessarily lethal. Embryo cells survived when crystal diameter was between 0·2 and 0·4 µm and fewer than 20 crystals were distributed per μm(2) in the cytoplasm. Ice was not uniformly distributed within the cells. In fully hydrated axes cooled at an intermediate rate, the interiors of many organelles were apparently ice-free; this may have prevented the disruption of vital intracellular machinery. Intracytoplasmic ice formation did not apparently impact the integrity of the plasmalemma. The maximum number of ice crystals was far greater in shoot apices, which were more sensitive than radicles to cryo-exposure. The findings challenge the accepted paradigm that intracellular ice formation is always lethal, as the results show that cells can survive intracellular ice if crystals are small and localized in the cytoplasm. Further understanding of the interactions among water content, cooling rate, cell structure and ice structure is required to optimize cryopreservation treatments without undue reliance on empirical approaches.

  4. PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres in murine embryonic stem cells.

    Science.gov (United States)

    Reynolds, Gloria E; Gao, Qing; Miller, Douglas; Snow, Bryan E; Harrington, Lea A; Murnane, John P

    2011-11-10

    Telomerase serves to maintain telomeric repeat sequences at the ends of chromosomes. However, telomerase can also add telomeric repeat sequences at DNA double-strand breaks (DSBs), a process called chromosome healing. Here, we employed a method of inducing DSBs near telomeres to query the role of two proteins, PIF1 and NBS1, in chromosome healing in mammalian cells. PIF1 was investigated because the PIF1 homolog in Saccharomyces cerevisiae inhibits chromosome healing, as shown by a 1000-fold increase in chromosome in PIF1-deficient cells. NBS1 was investigated because the functional homolog of NBS1 in S. cerevisiae, Xrs2, is part of the Mre11/Rad50/Xrs2 complex that is required for chromosome healing due to its role in the processing of DSBs and recruitment of telomerase. We found that disruption of mPif1 had no detectable effect on the frequency of chromosome healing at DSBs near telomeres in murine embryonic stem cells. Moreover, the Nbs1(ΔB) hypomorph, which is defective in the processing of DSBs, also had no detectable effect on the frequency of chromosome healing, DNA degradation, or gross chromosome rearrangements (GCRs) that result from telomeric DSBs. Although we cannot rule out small changes in chromosome healing using this system, it is clear from our results that knockout of PIF1 or the Nbs1(ΔB) hypomorph does not result in large differences in chromosome healing in murine cells. These results represent the first genetic assessment of the role of these proteins in chromosome healing in mammals, and suggest that murine cells have evolved mechanisms to ensure the functional redundancy of Pif1 or Nbs1 in the regulation of chromosome healing. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2012-01-01

    Full Text Available Background/Aim. Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. Methods. Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatographyultraviolet (HPLC-UV method. Results. A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43 was similar to the mean ratio after its administration in therapeutic doses (0.39, but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. Conclusion. Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine.

  6. Physicochemical and mechanical properties of carbamazepine cocrystals with saccharin.

    Science.gov (United States)

    Rahman, Ziyaur; Samy, Raghu; Sayeed, Vilayat A; Khan, Mansoor A

    2012-01-01

    The aim of present research was to investigate the physicochemical, mechanical properties, and stability characteristics of cocrystal of carbamazepine (CBZ) using saccharin (SAC) as a coformer. The cocrystals were prepared by solubility method and characterized by pH-solubility profile, intrinsic dissolution by static disk method, and surface morphology by scanning electron microscopy (SEM), crystallinity by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), and mechanical properties by Heckel analysis. Stability of the cocrystals were assessed by storing them at 60 (°)C for two weeks, 25 (°)C/60%RH, 40 (°)C/75%RH and 40 (°)C/94%RH for one month and compared with the stability of CBZ. The solubility profile of cocrystal was similar to CBZ. The cocrystal and CBZ have shown the same stability profile at all the conditions of studies except at 40 (°)C/94%RH. Unlike the CBZ, cocrystal was stable against dihydrate transformation. The compacts of cocrystal have a greater tensile strength and more compressibility. The Heckel analysis suggested that plastic deformation started at low compression pressure in the cocrystal than CBZ. In summary, the cocrystal form of carbamazepine provides another avenue for product development which is more stable than the parent drug.

  7. Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

    Directory of Open Access Journals (Sweden)

    Massimo Calderazzo

    2015-06-01

    Full Text Available We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6. The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml.

  8. Influence of kinnow juice on the bioavailability of carbamazepine in healthy male volunteers.

    Science.gov (United States)

    Garg, S K; Bhargava, V K; James, H; KuJan-Mar, N; Prabhakar, S; Naresh, Ku

    1998-01-01

    Kinnow juice produces a marked and variable increase in carbamazepine bioavailability. The pharmacokinetics of carbamazepine was studied after drug administration with 300 ml water or kinnow juice in a randomized cross over trial on nine healthy male volunteers. With kinnow juice peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) was significantly (P kinnow juice enhances carbamazepine bioavailability could be due to inhibition of cytochrome P-450 enzyme, since kinnow juice contains naringin which is considered to be inhibitor of liver microsomal dihydropyridine oxidation.

  9. Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data.

    Science.gov (United States)

    Akiskal, Hagop S; Fuller, Matthew A; Hirschfeld, Robert M A; Keck, Paul E; Ketter, Terence A; Weisler, Richard H

    2005-06-01

    This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on

  10. Palatal tremor after lithium and carbamazepine use: a case report

    Directory of Open Access Journals (Sweden)

    Kuruvilla Anju

    2010-06-01

    Full Text Available Abstract Introduction Palatal tremor, characterized by rhythmic contractions of the soft palate, can occur secondary to pathology in the dentato-rubro-olivary pathway, or in the absence of such structural lesions. Its pathogenesis is only partially understood. We describe a case of probable drug-induced palatal tremor. Case presentation A 27-year-old Indian man had taken carbamazepine and lithium for 7 years for the treatment of a manic episode. He presented with a one-year history of bilateral rhythmic oscillations of his soft palate and tremors of his tongue. There were no other abnormalities detected from his examination or after detailed investigation. Conclusion Palatal tremors may result from medication used in the treatment of psychiatric disorders.

  11. Carbamazepine and carbamazepine-10,11-epoxide clearance measurements during continuous venovenous hemofiltration in a massive overdose.

    Science.gov (United States)

    Smollin, Craig Geoffrey; Petrie, Matthew S; Kearney, Thomas

    2016-06-01

    Carbamazepine (CBZ) overdose can result in significant neurologic and cardiovascular toxicity, and is compounded by the presence of an active metabolite, carbamazepine-10,11-epoxide (CBZE). Existing publications describing continuous venovenous hemofiltration (CVVH) in CBZ overdose are limited in their ability to calculate accurate clearances. We report a case of CBZ overdose treated with CVVH with detailed measurement of CBZ, CBZE and their respective clearances calculated utilizing serial effluent measurements. This was coupled with serum level determinations comparing two analytical methodologies, time-of-flight mass spectroscopy and an immunoassay. A 41-year-old woman presented unresponsive after an overdose of CBZ. Initial CBZ serum levels were markedly elevated (57.8 μg/mL) and continued to rise. Due to continued hemodynamic instability, extracorporeal removal was initiated using CVVH. During the first 30 h of CVVH, interval serum samples and all ultrafiltrate bags were collected and analyzed. Serum and effluent levels of CBZ and CBZE were measured using an Agilent 6230 time-of-flight high-resolution mass spectrometer (TOF-MS). CBZ levels were also obtained utilizing the Microgenics CEDIA Carbamazepine Immunoassay (Thermo Fisher, Waltham, MA) for serum and effluent samples. Immunoassay analysis was performed using Siemens ADVIA 1800 instrument. The clearances achieved for CBZE (mean = 25.2, range 17.7-42.6 mL/min) exceeded that for CBZ (mean = 18.1, range 12.7-28.7 mL/min). CVVH removed a total of 1293 and 1261 mg of CBZ and CBZE, respectively. Serum levels of CBZ measured by immunoassay when compared with TOF-MS indicated cross reactivity of CBZE with the immunoassay. CVVH removed CBZE with higher clearances than CBZ. However, CVVH clearance rates for both CBZ and CBZE were lower than published clearances of CBZ and CBZE by intermittent hemodialysis. Our methodology allowed for a precise pharmacokinetic assessment of clearance based on

  12. Cysteamine supplementation during in vitro maturation of slaughterhouse- and opu-derived bovine oocytes improves embryonic development without affecting cryotolerance, pregnancy rate, and calf characteristics.

    Science.gov (United States)

    Merton, J S; Knijn, H M; Flapper, H; Dotinga, F; Roelen, B A J; Vos, P L A M; Mullaart, E

    2013-09-01

    Optimization of ovum pick up (OPU) followed by in vitro embryo production (IVP) is strongly driven by the needs of both beef and dairy cattle breeders to enhance genetic improvement. The rapidly growing use of genomic selection in cattle has increased the interest in using OPU-IVP technology to increase the number of embryos and offspring per donor, thus allowing enhanced selection intensity for the next generation. The aim of this study was to optimize embryo production through supplementation of cysteamine during in vitro maturation (IVM) and in vitro culture (IVC) of both slaughterhouse- and OPU-derived oocytes. The effects on embryo production and on embryo cryotolerance, post-transfer embryo survival, and calf characteristics, including gestation length, birth weight, perinatal mortality, and sex ratio were studied. In study 1, immature slaughterhouse-derived cumulus-oocyte complexes (COCs) were matured in IVM medium supplemented with or without 0.1 mM cysteamine, fertilized and cultured for 7 days in 0.5 ml SOFaaBSA. In study 2, cysteamine was present during both IVM (0.1 mM) and IVC (0.01, 0.05, 0.1 mM) from Days 1 to 4. In study 3, OPU-derived COCs were matured in medium supplemented with or without 0.1 mM cysteamine in a 2 × 2 factorial design (OPU week and cysteamine treatment). Embryos were evaluated for stage and grade on Day 7 and, depending on the number of transferable embryos and recipients available, the embryos were transferred either fresh or frozen-thawed at a later date. The presence of cysteamine during IVM significantly increased the embryo production rate with slaughterhouse-derived COCs (24.0% vs. 19.4%). The higher number of embryos at Day 7 was due to an increased number of blastocysts, whereas the distribution of embryos among different quality grades and cryotolerance was not affected. Embryo production rate was negatively affected when cysteamine was present during both the processes of IVM and IVC during Days 1 to 4 of culture (13

  13. Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

    Science.gov (United States)

    Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

    2007-04-01

    The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

  14. Relation between serum vitamin B12 level and duration of treatment with carbamazepine in epilepsy patients

    Directory of Open Access Journals (Sweden)

    Mohammad Tariqul Islam

    2016-12-01

    Full Text Available Vitamin B12 levels in the serum of 58 epileptic patients receiving only carbamazepine for at least 6 months were measured. Same number of epilepsy patients with no history of taking antiepileptic medicine were taken as control. The mean level of vitamin B12 in carbamazepine-treated epileptic patients was 265.5 pg/mL whereas it was 478.3 pg/mL in control. Increased duration of treatment of carbamazepine in epilepsy caused significantly decreased level of serum vitamin B12 (Pearson correlation coefficient, r = -0.9, p<0.0001. In conclusion, serum vitamin B12 level significantly decreased in relation to duration of carbamazepine treatment in epileptic patients.

  15. Parkinsonisme na toevoeging van fluoxetine aan behandeling met neuroleptica of carbamazepine

    NARCIS (Netherlands)

    Touw, D J; Gernaat, H B; van der Woude, J

    1992-01-01

    This article describes three patients who developed parkinsonism when fluoxetine was added to their existing medication (neuroleptics or carbamazepine). Based on published pharmacological and neuroanatomical research we postulate a serotonin-dopamine antagonism to be operative in the development of

  16. Study of efficacy of the combination of carbamazepine with nootropics on cognitive processes in epilepsy

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    Ivanov A.V.

    2013-03-01

    Full Text Available The authors studied the efficacy of combination of carbamazepine with nootropic drugs on cognitive processes in patients with epilepsy in experiment in order to reduce the side effects of anticonvulsant therapy. Analysis of anticonvulsant effect of the combination of drugs was carried out on 36 white nonlinear rats of both sexes weighing 160-180 g by the method of maximum electroshock, and the analysis of antiamnestic effect - using a model of retrograde amnesia on 80 white adult male rats weighing 160 - 200 g. For studying the mnemotropic activity of drug, the method of the conditioned reflex of active avoidance was used. The authors discovered that the isolated use of carbamazepine has the most negative influence on cognitive processes in animals, namely the formation of skill, memory engrams and consolidating memory trace as compared with the combined use of carbamazepine with neuroprotective drugs. It was found that the use of combinations of carbamazepine and nootropics in the experiment does not prevent the development of seizures completely, however, these combination can significantly reduce the duration of seizures (p <0.0001. Study of the effectiveness of the combined use of carbamazepine with nootropic drugs, revealed, that the tested drug combinations have a positive effect on cognitive processes and show neuroprotective effect on the brain structures of animals. The revealed effects of combined use of carbamazepine with nootropic drugs by the strength and intensity of the impact is much higher than isolated, while using carbamazepine. It was found, that the most effective combination is a combination of carbamazepine with Gliatilin.

  17. Solid-vapor interactions: Influence of environmental conditions on the dehydration of carbamazepine dihydrate

    OpenAIRE

    Surana, Rahul; Pyne, Abira; Suryanarayanan, Raj

    2003-01-01

    The goal of this research was a phenomenological study of the effect of environmental factors on the dehydration behavior of carbamazepine dihydrate. Dehydration experiments were performed in an automated vapor sorption apparatus under a variety of conditions, and weight loss was monitored as a function of time. In addition to lattice water, carbamazepine dihydrate contained a significant amount of physically bound water. Based on the kinetics of water loss, it was possible to differentiate b...

  18. The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures.

    Science.gov (United States)

    Donati, Filippo; Gobbi, Giuseppe; Campistol, Jaume; Rapatz, Guenter; Daehler, Maja; Sturm, Yvonne; Aldenkamp, Albert P

    2007-12-01

    To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

  19. CNS embryonal tumours: WHO 2016 and beyond.

    Science.gov (United States)

    Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

    2018-02-01

    Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

  20. Porcine embryonic stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2008-01-01

    The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences...

  1. Carbamazepine-Induced Acute Generalized Exanthematous Pustulosis: A Case Report

    Science.gov (United States)

    Skalli, Saadia; Barret, Pierre; Villier, Céline; Bussières, Jean-François

    2011-01-01

    A 15-year-old adolescent was admitted to the hospital for management of a generalized pruritic skin rash, which had appeared 10 days prior to admission. Carbamazepine (CBZ) and insulin were initiated 44 and 23 days prior to the onset of the skin rash (day 44), respectively. Clinical examination showed bluish lesions on the tongue and bilateral keratoconjunctivitis. His skin was very erythematous and pruritic without edema and covered with hundreds of nonfollicular pustules mainly on the trunk and skin folds. Laboratory assessment revealed leukocytosis, hypereosinophilia, and thrombocytopenia. A sample of superficial pus from a pustule on the trunk showed a significant number of leukocytes as well as a significant number of Staphylococcus aureus and Lancefield Group B β-hemolytic streptococci strains. An abdominal skin biopsy revealed acute to subacute folliculocentric spongiotic dermatitis with subcorneal pustules. All of these observations were consistent with a diagnosis of acute generalized exanthematous pustulosis (AGEP). Although we could not exclude with certainty the role of insulin initiated on day 21 and discontinued on day 55 with substitution to oral metformin and repaglinide, no cases of AGEP have ever been published with insulin, and skin lesions were not related to injection sites. This article describes a probable case of CBZ-induced acute generalized exanthematous pustulosis in a 15-year-old adolescent. PMID:22477826

  2. Pulsed corona discharge oxidation of aqueous carbamazepine micropollutant.

    Science.gov (United States)

    Ajo, Petri; Krzymyk, Ewelina; Preis, Sergei; Kornev, Iakov; Kronberg, Leif; Louhi-Kultanen, Marjatta

    2016-08-01

    The anti-epileptic drug carbamazepine (CBZ) receives growing attention due to slow biodegradation and inherent accumulation in the aquatic environment. The application of a gas-phase pulsed corona discharge (PCD) was investigated to remove CBZ from synthetic solutions and spiked wastewater effluent from a municipal wastewater treatment facility. The treated water was showered between high voltage (HV) wires and grounded plate electrodes, to which ultra-short HV pulses were applied. CBZ was readily oxidized and 1-(2-benzaldehyde)-4-hydroquinazoline-2-one (BQM) and 1-(2-benzaldehyde)-4-hydro-quinazoline-2,4-dione (BQD) were identified as the most abundant primary transformation products, which, contrary to CBZ ozonation data available in the literature, were further easily oxidized with PCD: BQM and BQD attributed to only a minor portion of the target compound oxidized. In concentrations commonly found in wastewater treatment plant effluents (around 5 µg L(-1)), up to 97% reduction in CBZ concentration was achieved at mere 0.3 kW h m(-3) energy consumption, and over 99.9% was removed at 1 kW h m(-3). The PCD application proved to be efficient in the removal of both the parent substance and its known transformation products, even with the competing reactions in the complex composition of wastewater.

  3. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.

    2017-01-01

    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  4. Assessment of the effects of the carbamazepine on the endogenous endocrine system of Daphnia magna.

    Science.gov (United States)

    Oropesa, A L; Floro, A M; Palma, P

    2016-09-01

    In the present study, the endocrine activity of the antiepileptic pharmaceutical carbamazepine (CBZ) in the crustacean Daphnia magna was assessed. To assess the hormonal activity of the drug, we exposed maternal daphnids and embryos to environmental relevant concentrations of CBZ (ranging from 10 to 200 μg/L) and to mixtures of CBZ with fenoxycarb (FEN; 1 μg/L). Chronic exposure to CBZ significantly decreased the reproductive output and the number of molts of D. magna at 200 μg/L. This compound induced the production of male offspring (12 ± 1.7 %), in a non-concentration-dependent manner, acting as a weak juvenile hormone analog. Results showed that this substance, at tested concentrations, did not antagonize the juvenoid action of FEN. Further, CBZ has shown to be toxic to daphnid embryos through maternal exposure interfering with their normal gastrulation and organogenesis stages but not producing direct embryo toxicity. These findings suggest that CBZ could act as an endocrine disruptor in D. magna as it decreases the reproductive output, interferes with sex determination, and causes development abnormality in offspring. Therefore, CBZ could directly affect the population sustainability.

  5. Effects of carbamazepine on dexamethasone suppression and sleep electroencephalography in borderline personality disorder.

    Science.gov (United States)

    De la Fuente, José M; Bobes, Julio; Vizuete, Coro; Mendlewicz, Julien

    2002-01-01

    The pathophysiology of borderline personality disorder (BPD) remains obscure, but there is mounting evidence of brain dysfunction without focal abnormality. The dexamethasone suppression test (DST) and sleep electroencephalography (sleep EEG) have been studied in BPD, but the findings seem to be related to a concomitant axis I diagnosis of major depression (MD) rather than to BPD itself. There is no effective treatment for BPD. Carbamazepine (CBZ) has shown contradictory results and in a previous study, our results were negative. In this study, we investigated the effects of CBZ versus placebo on the DST and sleep EEG in a sample of 20 BPD patients without concomitant MD. CBZ given at doses that are therapeutic for epilepsy and affective disorders may have an effect on the DST and sleep EEG in BPD. CBZ significantly increased the postdexamethasone plasma cortisol values. This did not parallel MD or an increase in the Hamilton depression rating scores. CBZ also increased slow wave sleep (SWS). The mechanisms by which CBZ increased postdexamethasone plasma cortisol levels and SWS in BPD are discussed. Copyright 2002 S. Karger AG, Basel

  6. Uptake of Carbamazepine by rhizomes and endophytic bacteria of Phragmites australis

    Directory of Open Access Journals (Sweden)

    Andres eSauvetre

    2015-02-01

    Full Text Available Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely in Europe and North America. In the environment, it is found as a persistent and recalcitrant conta¬mi-nant, being one of the most prominent hazardous pharmaceuticals and personal care products (PPCPs in effluents of wastewater treatment plants (WWTPs. Phragmites australis is one of the species with both, the highest potential of detoxification and phytoremediation. It has been used successfully in the treatment of industrial and municipal wastewater. Recently, the identification of endophytic micro¬organisms from different plant species growing in contaminated sites has provided a list of candidates which could be used as bio-inoculants for bioremediation of difficult compounds. In this study, Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days the plants had removed 90% of the initial concentration. Endophytic bacteria were isolated from these plants and further characterized. Phylogenetic analysis based on 16S rDNA sequencing revealed that the majority of these isolates belong to three groups: Proteobacteria, Actinobacteria and Bacteroidetes. Carbamazepine uptake and plant growth promoting (PGP traits were analyzed among the isolates. Ninety percent of the isolates produce indole acetic acid (IAA and all of them possess at least one of the PGP traits tested. One isolate identified as Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP traits. Rhizobium daejeonense can remove carbamazepine and produces 23 µg/mL of IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show high siderophore production and phosphate solubilization. Alone or in combination, these isolates might be applied as inoculates in constructed wetlands in order to enhance the phyto-remediation of carbamazepine during wastewater

  7. Phenytoin and carbamazepine in trigeminal neuralgia: marketing-based versus evidence-based treatment

    Directory of Open Access Journals (Sweden)

    Keppel Hesselink JM

    2017-07-01

    Full Text Available Jan M Keppel Hesselink,1 Michael E Schatman2,31Institute for Neuropathic Pain, Bosch en Duin, the Netherlands; 2Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 3Boston Pain Care, Waltham, MA, USAIntroductionMost review articles support carbamazepine as a first-line pharmacotherapy for idiopathic trigeminal neuralgia.1–3 However, the empirical support for this recommendation is somewhat suspect. Phenytoin, as the prototype for all anticonvulsants, was already positioned as an analgesic compound 70 years ago. Since these initial findings, the data that have been gathered have supported the use of anticonvulsants as painkillers – from phenytoin up to and including more recent anticonvulsants such as gabapentin and pregabalin. Since 1942, a number of papers supported phenytoin’s therapeutic effects in trigeminal neuralgia (Table 1. The introduction of carbamazepine in 1962 by Geigy shifted the interest of neurologists from phenytoin as a treatment for trigeminal neuralgia to carbamazepine, without sound scientific evidence. To date, no convincing randomized controlled trials (RCTs have been published supporting the role of carbamazepine in trigeminal neuralgia, and we could not identify a single study comparing the effects of phenytoin with those of carbamazepine. Accordingly, phenytoin should probably be considered more often as a viable therapy for (treatmentresistant trigeminal neuralgia.

  8. Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy.

    Science.gov (United States)

    Berghuis, Bianca; van der Palen, Job; de Haan, Gerrit-Jan; Lindhout, Dick; Koeleman, Bobby P C; Sander, Josemir W

    2017-07-01

    To ascertain possible determinants of carbamazepine (CBZ)- and oxcarbazepine (OXC)-induced hyponatremia in a large cohort of people with epilepsy. We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L. We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively. Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  9. Sirenomelia after phenobarbital and carbamazepine therapy in pregnancy.

    Science.gov (United States)

    Tica, Oana Sorina; Tica, Andrei Adrian; Brailoiu, Cristina Gabriela; Cernea, Nicolae; Tica, Vlad Iustin

    2013-06-01

    Epilepsy still remains a serious challenge for any obstetrician due to the potential teratogenicity of all antiepileptics. However, without appropriate maternal therapy the seizures can reappear, with direct negative impact on fetus. Currently, sirenomelia is the most severe caudal pole dysgenesis, consequent to an abnormal vascular supply development in the fetal lower body. We report a stillborn, GA/LMP = 37 weeks, delivered by an epileptic woman, who received in the first four months of pregnancy phenobarbital (PH) 0.1 g/day and carbamazepine (CMZ) 0.4 g/day, followed only by PH 0.1 g/day, until delivery. The stillborn, weighing 2200 g, presented sirenomelia type II, with some of its "classic" features: oligohydramnios, absence of kidneys, bladder, rectum, uterus, and a single umbilical artery. Some other "particularities" included: no Potter's facies and no significant cardio-pulmonary abnormalities. Since PH and CMZ alone are responsible, commonly, for mild abnormalities, we hypothesized that combined therapy with PH and CMZ (both strong enzyme-inductors, especially PH) potentiated their teratogenicity, by producing supplementary quantities of epoxides and/or other oxides, which accumulated in the fetal tissues. Except for sirenomelia, all other mild abnormalities, theoretically associated with "fetal CMZ and/or PH syndrome," are rarely observed, fact which demonstrates the drug-drug interactions between the two antiepileptics. This report highlights the possibility that PH/CBZ therapy during fetal organogenesis can induce sirenomelia, by a synergistic teratogenic effect and support the recommendation to use only one drug in pregnant epileptic women. A careful ultrasound monitoring of these patients is mandatory due to the teratogenic risk of both seizures and therapy. Copyright © 2013 Wiley Periodicals, Inc.

  10. Anti-solvent co-crystallization of carbamazepine and saccharin.

    Science.gov (United States)

    Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

    2013-06-25

    The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Pharmacokinetics: time-dependent changes--autoinduction of carbamazepine epoxidation

    International Nuclear Information System (INIS)

    Bertilsson, L.; Tomson, T.; Tybring, G.

    1986-01-01

    Drugs labeled with stable isotopes have been useful to study time-dependent changes in kinetics. Early studies suggested that carbamazepine (CBZ) may induce its own metabolism, but this could not be proved until tetradeuterium-labeled CBZ (CBZ-D4) was synthesized and then given to patients. CBZ-D4 was administered to three children during long-term treatment of epilepsy with CBZ. After 17 to 32 days of treatment, the plasma clearance of CBZ-D4 was doubled, but during the next four months, there was no further increase, indicating that autoinduction was complete within one month. Two patients with chronic alcoholism were treated with CBZ for five days. Half of the first dose of 600 mg was comprised of CBZ-D4. The half-life of this CBZ-D4 dose in the two patients (20 and 26 hr, respectively) was similar to the post-steady-state half-life of CBZ (23 hr in both patients) measured later. A single dose of CBZ given one week after the last maintenance dose had a longer half-life (46 and 45 hr, respectively), which probably is close to the disposition of the drug before starting the treatment with CBZ. This shows that autoinduction of CBZ metabolism was completed during the very first doses of CBZ. Autoinduction also disappeared rapidly after stopping the treatment. We have shown that it is mainly the epoxide-diol pathway that is induced, both during autoinduction and after induction with other antiepileptic agents

  12. Comparative efficacy of phenytoin, steroid and carbamazepine in herpes zoster and post herpetic neuralgia

    Directory of Open Access Journals (Sweden)

    Agarwal S

    1991-01-01

    Full Text Available Three hundred patients of different ages were sequentially assigned three therapy groups (100 in each group viz. phenytoin, steroid (prednisolone and carbamazepine. Effect of these drugs on herpes zoster neuralgia and in prevention of post herpetic neuralgia was studied. Phenytoin was found to be superior to both steroid and carbamazepine in relieving the pain of herpes zoster and in reducing the incidence of post herpetic neuralgia. Only 16.1% of the patients in phenytoin treated group developed post herpetic neuralgia lasting for 2-4 weeks while 22.7% and 29.6% of the steroid and carbamazepine treated patients respectively developed post herpetic neuralgia and that too lasting for longer duration. No patient under 40 years developed post herpetic neuralgia.

  13. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

    Directory of Open Access Journals (Sweden)

    Prasanna A. Datar

    2015-08-01

    Full Text Available Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application. Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quantitative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enumerates metabolites, and impurities reported so far. Keywords: Carbamazepine, HPLC, LC–MS/MS, HPTLC, RP-UFLC, Micellar electrokinetic chromatography

  14. Degradation of orange dyes and carbamazepine by soybean peroxidase immobilized on silica monoliths and titanium dioxide.

    Science.gov (United States)

    Calza, Paola; Zacchigna, Dario; Laurenti, Enzo

    2016-12-01

    In this paper, the removal of three common dyes (orange I, orange II, and methylorange) and of the anticonvulsant drug carbamazepine from aqueous solutions by means of enzymatic and photocatalytic treatment was studied. Soybean peroxidase (SBP) was used as biocatalyst, both free in solution and immobilized on silica monoliths, and titanium dioxide as photocatalyst. The combination of the two catalysts led to a faster (about two to four times) removal of all the orange dyes compared to the single systems. All the dyes were completely removed within 2 h, also in the presence of immobilized SBP. As for carbamazepine, photocatalytic treatment prevails on the enzymatic degradation, but the synergistic effect of two catalysts led to a more efficient degradation; carbamazepine's complete disappearance was achieved within 60 min with combined system, while up to 2 h is required with TiO 2 only.

  15. Association of HLA-BFNx011502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians

    Directory of Open Access Journals (Sweden)

    Mehta Timir

    2009-01-01

    Full Text Available Background: Stevens-Johnson Syndrome (SJS and toxic epidermal necrolysis are severe cutaneous reactions caused by certain drugs, including antiepileptic carbamazepine. A strong association has been reported between human leucocyte antigen (HLA-BFNx011502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-BFNx011502 is not a universal marker but is ethnicity-specific for Asians. Aim: To study the association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients. Methods: Eight individuals who fulfilled the diagnostic criteria of SJS induced by carbamazepine were identified and HLA-B molecular typing was performed. HLA-B genotyping was carried out by polymerase chain reaction using sequence-specific primers. Results: Out of eight patients studied for genotype, six patients were found to have the HLA-BFNx011502 allele. Conclusion: This study suggests an association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients.

  16. CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

    Directory of Open Access Journals (Sweden)

    Milovanovic Dragana Dragas

    2015-06-01

    Full Text Available Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08, indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26, higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47 and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79 of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

  17. Biomimetic oxidation of carbamazepine with hydrogen peroxide catalyzed by a manganese porphyrin

    Directory of Open Access Journals (Sweden)

    Cláudia M. B. Neves

    2012-01-01

    Full Text Available This laboratory project is planned for an undergraduate chemistry laboratory in which students prepare a manganese porphyrin able to mimic the oxidative metabolism of carbamazepine, one of the most frequently prescribed drugs in the treatment of epilepsy. The in vitro oxidation of carbamazepine results in the formation of the corresponding 10,11-epoxide, the main in vivo metabolite. The reaction is catalyzed by manganese porphyrin in the presence of H2O2, an environmentally-friendly oxidant. Through this project students will develop their skills in organic synthesis, coordination chemistry, chromatographic techniques such as TLC and HPLC, UV-visible spectrophotometry, and NMR spectroscopy.

  18. Biomimetic oxidation of carbamazepine with hydrogen peroxide catalyzed by a manganese porphyrin

    Energy Technology Data Exchange (ETDEWEB)

    Neves, Claudia M.B.; Simoes, Mario M.Q.; Domingues, Fernando M.J.; Neves, M. Graca P.M.S.; Cavaleiro, Jose A.S., E-mail: msimoes@ua.pt [Dept. de Quimica, QOPNA, Universidade de Aveiro (Portugal)

    2012-07-01

    This laboratory project is planned for an undergraduate chemistry laboratory in which students prepare a manganese porphyrin able to mimic the oxidative metabolism of carbamazepine, one of the most frequently prescribed drugs in the treatment of epilepsy. The in vitro oxidation of carbamazepine results in the formation of the corresponding 10,11-epoxide, the main in vivo metabolite. The reaction is catalyzed by manganese porphyrin in the presence of H{sub 2}O{sub 2}, an environmentally-friendly oxidant. Through this project students will develop their skills in organic synthesis, coordination chemistry, chromatographic techniques such as TLC and HPLC, UV-visible spectrophotometry, and NMR spectroscopy. (author)

  19. Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine.

    Science.gov (United States)

    Pirmohamed, M; Graham, A; Roberts, P; Smith, D; Chadwick, D; Breckenridge, A M; Park, B K

    1991-01-01

    1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1768568

  20. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Akute, O.

    1999-02-01

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  1. A retrospective study of carbamazepine therapy in the treatment of idiopathic generalised epilepsy

    LENUS (Irish Health Repository)

    O'Connor, G

    2011-05-01

    Objective: The exacerbation of idiopathic generalised epilepsy (IGE) by some anti-epileptic drugs (AEDs) such as carbamazepine (CBZ) has been well documented. However, it is unclear whether IGE is always worsened by the use of CBZ, or whether some patients with IGE benefit from its use. \\r\

  2. Relaxation and crystallization of amorphous carbamazepine studied by terahertz pulsed spectroscopy

    DEFF Research Database (Denmark)

    Zeitler, J Axel; Taday, Philip F; Pepper, Michael

    2007-01-01

    At the example of carbamazepine the crystallization of a small organic molecule from its amorphous phase was studied using in situ variable temperature terahertz pulsed spectroscopy (TPS). Even though terahertz spectra of disordered materials in the glassy state exhibit no distinct spectral featu...

  3. Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study

    Directory of Open Access Journals (Sweden)

    Thaiana Aragão Santana

    Full Text Available CONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV.DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life.RESULTS:None of the ten patients (0% presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life.CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population.

  4. Visualizing solvent mediated phase transformation behavior of carbamazepine polymorphs by principal component analysis

    DEFF Research Database (Denmark)

    Tian, Fang; Rades, Thomas; Sandler, Niklas

    2008-01-01

    The purpose of this research is to gain a greater insight into the hydrate formation processes of different carbamazepine (CBZ) anhydrate forms in aqueous suspension, where principal component analysis (PCA) was applied for data analysis. The capability of PCA to visualize and to reveal simplified...

  5. Intrauterine exposure to carbamazepine and specific congenital malformations : systematic review and case-control study

    NARCIS (Netherlands)

    Jentink, Janneke; Dolk, Helen; Loane, Maria A.; Morris, Joan K.; Wellesley, Diana; Garne, Ester; de Jong-van den Berg, Lolkje

    2010-01-01

    Objective To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. Design A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. Setting Review of

  6. Effect of pomegranate juice pre-treatment on the transport of carbamazepine across rat intestine

    Directory of Open Access Journals (Sweden)

    D Adukondalu

    2010-12-01

    Full Text Available "n  "nBackground and the purpose of the study: Many drug substances along with a variety of naturally occurring dietary or herbal components interact with the CYP enzyme system.The present study was aimed to investigate the effect of pomegranate juice pre-treatment on the transport of carbamazepine across the rat intestine "nMethods: The transport of carbamazepine across different parts of rat intestine was studied by everted and non-everted sac methods. The control and pomegranate juice (10 ml Kg-1 for 7 days pre-treated rats were sacrificed and isolated the intestine. The sacs of intestine were prepared, treated with carbamazepine solution and then placed in dulbeccos buffer. Samples were collected periodically and the drug content was estimated using HPLC. Results and conclusion: The results show that there was a significant (p<0.05 difference in the transport of carbamazepine from the intestinal sacs of pretreated with pomegranate juice and control. It seems that pomegranatejuice might have induced CYP3A4enzymes and hence drug is extensively metabolized.

  7. Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup

    Science.gov (United States)

    Ghannoum, Marc; Yates, Christopher; Galvao, Tais F.; Sowinski, Kevin M.; Vo, Thi Hai Vân; Coogan, Andrew; Gosselin, Sophie; Lavergne, Valery; Nolin, Thomas D.; Hoffman, Robert S.

    2014-01-01

    Abstract Context. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Objectives. To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning. Methods. After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results. Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous

  8. Few-Layer MoS2 Nanodomains Decorating TiO2 Nanoparticles: A Case Study for the Photodegradation of Carbamazepine

    Directory of Open Access Journals (Sweden)

    Sara Cravanzola

    2018-03-01

    Full Text Available S-doped TiO2 and hybrid MoS2/TiO2 systems have been synthesized, via the sulfidation with H2S of the bare TiO2 and of MoOx supported on TiO2 systems, with the aim of enhancing the photocatalytic properties of TiO2 for the degradation of carbamazepine, an anticonvulsant drug, whose residues and metabolites are usually inefficiently removed in wastewater treatment plants. The focus of this study is to find a relationship between the morphology/structure/surface properties and photoactivity. The full characterization of samples reveals the strong effects of the H2S action on the properties of TiO2, with the formation of defects at the surface, as shown by transmission electron microscopy (TEM and infrared spectroscopy (IR, while also the optical properties are strongly affected by the sulfidation treatment, with changes in the electronic states of TiO2. Meanwhile, the formation of small and thin few-layer MoS2 domains, decorating the TiO2 surface, is evidenced by both high-resolution transmission electron microscopy (HRTEM and UV-Vis/Raman spectroscopies, while Fourier-transform infrared (FTIR spectra give insights into the nature of Ti and Mo surface sites. The most interesting findings of our research are the enhanced photoactivity of the MoS2/TiO2 hybrid photocatalyst toward the carbamazepine mineralization. Surprisingly, the formation of hazardous compounds (i.e., acridine derivatives, usually obtained from carbamazepine, is precluded when treated with MoS2/TiO2 systems.

  9. Embryonic vaccines against cancer: an early history.

    Science.gov (United States)

    Brewer, Bradley G; Mitchell, Robert A; Harandi, Amir; Eaton, John W

    2009-06-01

    Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

  10. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

    Energy Technology Data Exchange (ETDEWEB)

    Kaushik, Gaurav, E-mail: kausgaur@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Department of Medical Pathology and Laboratory Medicine, University of California at Davis, Davis, CA 95817 (United States); Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817 (United States); Huber, David P., E-mail: hubedavi@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Aho, Ken, E-mail: ahoken@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Finney, Bruce, E-mail: finney@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Bearden, Shawn, E-mail: bearshaw@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States); Zarbalis, Konstantinos S., E-mail: kzarbalis@ucdavis.edu [Department of Medical Pathology and Laboratory Medicine, University of California at Davis, Davis, CA 95817 (United States); Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817 (United States); Thomas, Michael A., E-mail: mthomas@isu.edu [Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave, Pocatello, ID 83209-8007 (United States)

    2016-05-27

    Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding {sup 2}H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post–conception days), and quantifying {sup 2}H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of {sup 2}H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at

  11. Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2009-01-01

    Full Text Available Background/Aim. Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Methods. Separation of the drug from matrix is achieved by reversedphase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1 at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10 using chlorophorm. Results. Calibration curves were in the range 0.1-5 μg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD of carbamazepine in serum and saliva were 0.166 and 0.178 μg/mL, respectively. Limits of quantification (LOQ in the serum and saliva were 0.237 and 0.226 μg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001. Conclusion. The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

  12. Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection.

    Science.gov (United States)

    Dordević, Snezana; Kilibarda, Vesna; Stojanović, Tomislav

    2009-05-01

    Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Separation of the drug from matrix is achieved by reversed-phase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1) at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10) using chlorophorm. Calibration curves were in the range 0.1-5 microg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD) of carbamazepine in serum and saliva were 0.166 and 0.178 microg/mL, respectively. Limits of quantification (LOQ) in the serum and saliva were 0.237 and 0.226 microg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001). The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

  13. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

    International Nuclear Information System (INIS)

    Kaushik, Gaurav; Huber, David P.; Aho, Ken; Finney, Bruce; Bearden, Shawn; Zarbalis, Konstantinos S.; Thomas, Michael A.

    2016-01-01

    Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding "2H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post–conception days), and quantifying "2H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of "2H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at typical

  14. A toolbox to explore the mechanics of living embryonic tissues

    Science.gov (United States)

    Campàs, Otger

    2016-01-01

    The sculpting of embryonic tissues and organs into their functional morphologies involves the spatial and temporal regulation of mechanics at cell and tissue scales. Decades of in vitro work, complemented by some in vivo studies, have shown the relevance of mechanical cues in the control of cell behaviors that are central to developmental processes, but the lack of methodologies enabling precise, quantitative measurements of mechanical cues in vivo have hindered our understanding of the role of mechanics in embryonic development. Several methodologies are starting to enable quantitative studies of mechanics in vivo and in situ, opening new avenues to explore how mechanics contributes to shaping embryonic tissues and how it affects cell behavior within developing embryos. Here we review the present methodologies to study the role of mechanics in living embryonic tissues, considering their strengths and drawbacks as well as the conditions in which they are most suitable. PMID:27061360

  15. Function of JARID2 in bovines during early embryonic development

    Directory of Open Access Journals (Sweden)

    Yao Fu

    2017-12-01

    Full Text Available Histone lysine modifications are important epigenetic modifications in early embryonic development. JARID2, which is a member of the jumonji demethylase protein family, is a regulator of early embryonic development and can regulate mouse development and embryonic stem cell (ESC differentiation by modifying histone lysines. JARID2 can affect early embryonic development by regulating the methylation level of H3K27me3, which is closely related to normal early embryonic development. To investigate the expression pattern of JARID2 and the effect of JARID2-induced H3K27 methylation in bovine oocytes and early embryonic stages, JARID2 mRNA expression and localization were detected in bovine oocytes and early embryos via qRT-PCR and immunofluorescence in the present study. The results showed that JARID2 is highly expressed in the germinal vesicle (GV, MII, 2-cell, 4-cell, 8-cell, 16-cell and blastocyst stages, but the relative expression level of JARID2 in bovine GV oocytes is significantly lower than that at other oocyte/embryonic stages (p < 0.05, and JARID2 is expressed primarily in the nucleus. We next detected the mRNA expression levels of embryonic development-related genes (OCT4, SOX2 and c-myc after JARID2 knockdown through JARID2-2830-siRNA microinjection to investigate the molecularpathwayunderlying the regulation of H3K27me3 by JARID2 during early embryonic development. The results showed that the relative expression levels of these genes in 2-cell embryos weresignificantly higher than those in the blastocyst stage, and expression levels were significantly increased after JARID2 knockdown. In summary, the present study identified the expression pattern of JARID2 in bovine oocytes and at each early embryonic stage, and the results suggest that JARID2 plays a key role in early embryonic development by regulating the expression of OCT4, SOX2 and c-myc via modification of H3K27me3 expression. This work provides new data for improvements in the

  16. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine

    International Nuclear Information System (INIS)

    Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

    2011-01-01

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  17. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Werickson Fortunato de Carvalho [Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); National Institute of Metrology, Standardization and Industrial Quality, Inmetro, Dimci/Dquim - Directorate of Metrology, Science and Industry/Division of Chemical Metrology, Av. Nossa Senhora das Gracas 50, Building 6, 25250-020, Xerem, Duque de Caxias, RJ (Brazil); Poppi, Ronei Jesus, E-mail: ronei@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); National Institute of Science and Technology (INCT) for Bioanalytics, 13083-970 Campinas, SP (Brazil)

    2011-10-31

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  18. Effect of carbamazepine (Tegretol) on seizure and EEG patterns in monkeys with alumina-induced focal motor and hippocampal foci.

    Science.gov (United States)

    David, J; Grewal, R S

    1976-12-01

    Qualitative and quantitative aspects of chronic carbamazepine (Tegretol) medication on focal seizures and associated interictal EEG abnormalities in Rhesus monkeys with alumina-induced foci in either the sensorimotor cortex or the hipocampus was investigated. In both groups of animals, carbamazepine produced qualitative control of visible seizures and reduced intracortical spike propagation, but did not cause complete normalization of the background EEG; quantitative indices, such as spike density and amount of paroxysmal discharge representative of abnormal EEG activity, were significantly reduced with respect to predrug values during medication and after cessation as well. Threshold to pentylenetetrazol was elevated by carbamazepine in both groups of epileptic monkeys. Aggressivity and other clinical manifestations in monekys with hippocampal foci were markedly reduced by carbamazepine.

  19. Embryonic duplications in sheep.

    Science.gov (United States)

    Dennis, S M

    1975-02-01

    Twenty-seven embryonic duplications were examined during a 3-year investigation into the causes of perinatal lamb mortality. Twenty of the 27 were anomalous twins with 19 being conjoined (diplopagus 9 and heteropagus 10). The various duplications were: haloacardius acephalus 1, diprosopus 2, dicephalus 2, dipypus 3, diprosopus dipygus 1, syncephalus dipygus 1, pygopagus parasiticus 1, heteropagus dipygus 3, melodidymus 6, polyury 4, penile duplication 2, and bilateral otognathia 1. Four lambs were living and the time of death of the others was: parturient 8, and post-parturient 15. Average dry weight of the lambs was 3.35 kg (range 1.59 to 5.45 kg). Breed distribution was: Merino 77.8%, Crossbred 14.8%, Dorset Horn 3.7%, and Corriedale 3.7%. The caudal region was involved in 10 of the conjoined twins (52.6%), anterior region in 7 (36.9%), and both anterior and caudal regions in 2 (10.5%). Associated defects were present in 70.4% of the 27 lambs, the most common being atresia ani.

  20. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

    Science.gov (United States)

    Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2008-01-01

    The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

  1. Patently controversial: markets, morals, and the President's proposal for embryonic stem cell research.

    Science.gov (United States)

    Fins, Joseph J; Schachter, Madeleine

    2002-09-01

    This essay considers the implications of President George W. Bush's proposal for human embryonic stem cell research. Through the perspective of patent law, privacy, and informed consent, we elucidate the ongoing controversy about the moral standing of human embryonic stem cells and their derivatives and consider how the inconsistencies in the president's proposal will affect clinical practice and research.

  2. A PLS-based extractive spectrophotometric method for simultaneous determination of carbamazepine and carbamazepine-10,11-epoxide in plasma and comparison with HPLC

    Science.gov (United States)

    Hemmateenejad, Bahram; Rezaei, Zahra; Khabnadideh, Soghra; Saffari, Maryam

    2007-11-01

    Carbamazepine (CBZ) undergoes enzyme biotransformation through epoxidation with the formation of its metabolite, carbamazepine-10,11-epoxide (CBZE). A simple chemometrics-assisted spectrophotometric method has been proposed for simultaneous determination of CBZ and CBZE in plasma. A liquid extraction procedure was operated to separate the analytes from plasma, and the UV absorbance spectra of the resultant solutions were subjected to partial least squares (PLS) regression. The optimum number of PLS latent variables was selected according to the PRESS values of leave-one-out cross-validation. A HPLC method was also employed for comparison. The respective mean recoveries for analysis of CBZ and CBZE in synthetic mixtures were 102.57 (±0.25)% and 103.00 (±0.09)% for PLS and 99.40 (±0.15)% and 102.20 (±0.02)%. The concentrations of CBZ and CBZE were also determined in five patients using the PLS and HPLC methods. The results showed that the data obtained by PLS were comparable with those obtained by HPLC method.

  3. Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine epoxide in human plasma by high-performance liquid chromatography with ultraviolet detection.

    Science.gov (United States)

    Bhatti, M M; Hanson, G D; Schultz, L

    1998-03-01

    The Bioanalytical Chemistry Department at the Madison facility of Covance Laboratories, has developed and validated a simple and sensitive method for the simultaneous determination of phenytoin (PHT), carbamazepine (CBZ) and 10,11-carbamazepine epoxide (CBZ-E) in human plasma by high-performance liquid chromatography with 10,11 dihydrocarbamazepine as the internal standard. Acetonitrile was added to plasma samples containing PHT, CBZ and CBZ-E to precipitate the plasma proteins. After centrifugation, the acetonitrile supernatant was transferred to a clean tube and evaporated under N2. The dried sample extract was reconstituted in 0.4 ml of mobile phase and injected for analysis by high-performance liquid chromatography. Separation was achieved on a Spherisorb ODS2 analytical column with a mobile phase of 18:18:70 acetonitrile:methanol:potassium phosphate buffer. Detection was at 210 nm using an ultraviolet detector. The mean retention times of CBZ-E, PHT and CBZ were 5.8, 9.9 and 11.8 min, respectively. Peak height ratios were fit to a least squares linear regression algorithm with a 1/(concentration)2 weighting. The method produces acceptable linearity, precision and accuracy to a minimum concentration of 0.050 micrograms ml-1 in human plasma. It is also simple and convenient, with no observable matrix interferences.

  4. Fatal Toxic Epidermal Necrolysis Induced by Carbamazepine Treatment in a Patient Who Previously had Carbamazepine-induced Stevens-Johnson Syndrome

    Directory of Open Access Journals (Sweden)

    Li-Yen Huang

    2007-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a rare but life-threatening skin disease that is most commonly drug-induced. It has recently been suggested that Stevens-Johnson syndrome (SJS belongs to the same group of skin disorders, although it has a lower mortality rate than TEN. We report the case of a 26-year-old male schizophrenic patient with a history of carbamazepine-induced SJS 5 years earlier. At the time of his current admission, he was admitted to our psychiatry department with acute agitation due to schizophrenia. However, the patient and his family denied history of drug allergy. After 3 days of carbamazepine treatment, the patient developed TEN (body surface area > 90%. He was transferred to the burn center, but despite appropriate treatment, including intravenous hydrocortisone 200 mg q6h and being covered with sterile biological material, he died. It is important to note that re-administration of a drug that previously caused SJS may lead to TEN, which has a very high mortality rate.

  5. Monitoring of carbamazepine concentrations in wastewater and groundwater to quantify sewer leakage.

    Science.gov (United States)

    Fenz, R; Blaschke, A P; Clara, M; Kroiss, H; Mascher, D; Zessner, M

    2005-01-01

    Monitoring of carbamazepine concentrations in wastewater and groundwater enables us to identify and quantify sewer exfiltration. The antiepileptic drug carbamazepine is hardly removed in wastewater treatment plants and not or just slightly attenuated during bank infiltration and subsoil flow. Concentrations in wastewater are generally 1000 times higher than the limit of quantification. In contrast to . many other wastewater tracers carbamazepine is discharged to the environment only via domestic wastewater. The results from this study carried out in Linz, Austria indicate an average exfiltration rate of 1%, expressed as percentage of the dry weather flow that is lost to the groundwater on the city-wide scale. This rate is lower than sewage losses reported in most other studies which attempted to quantify exfiltration on the basis of groundwater pollution. However, it was also possible to identify one area with significantly higher sewage losses. This method seems to be very suitable for the verification of leakage models used to assess sewer exfiltration on a regional scale.

  6. Amorphous is not always better—A dissolution study on solid state forms of carbamazepine

    DEFF Research Database (Denmark)

    Jensen, Linda G.; Skautrup, Frederik B.; Müllertz, Anette

    2017-01-01

    state forms of carbamazepine, crystalline or amorphous drug, with or without either polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) and glass solutions of the drug with both polymers (2:1, 4:1 and 10:1 (w/w) drug-to-polymer ratio) were tested with respect to their dissolution behaviour...... in a biorelevant gastric medium (for 30 min) and subsequently in intestinal conditions (for 2 h). Carbamazepine form III in the absence of polymer dissolved to a drug concentration of 540 μg/ml, but the concentration decreased after around 70 min due to precipitation of the dihydrate form, and reached 436 μg....../ml after 2.5 h dissolution testing. The presence of PVP led to a similar dissolution profile with a slightly earlier onset of decrease in drug concentration, while in the presence of HPMC no decline in dissolved drug concentration was observed. Surprisingly, amorphous carbamazepine did not result in any...

  7. Mass balance analysis of triclosan, diethyltoluamide, crotamiton and carbamazepine in sewage treatment plants.

    Science.gov (United States)

    Nakada, N; Yasojima, M; Okayasu, Y; Komori, K; Suzuki, Y

    2010-01-01

    The behavior of antibacterial triclosan, insect-repellent diethyltoluamide (DEET), anticonvulsant carbamazepine, and antipruritic crotamiton was investigated at two sewage treatment plants (STPs) to clarify their complete mass balance. Twenty-four-hour flow-proportional composite samples were collected from the influent and effluent of primary and final sedimentation tanks, a biofiltration tank and disinfection tanks. Sludge samples (i.e., activated and excess sludge) and samples of the return flow from the sludge treatment process were collected in the same manner. The analytes in both the dissolved and particulate phases were individually determined by a gas chromatograph equipped with mass spectrometer. Triclosan was dominantly detected in the particulate phase especially in the early stage of treatment (up to 83%) and was efficiently removed (over 90%) in STPs, mainly by sorption to sewage sludge. Limited removal was observed for DEET (55+/-24%), while no significant removal was demonstrated for crotamiton or carbamazepine. The solid-water distribution coefficients (K(d), n=4) for triclosan (log K(d): 3.7-5.1), DEET (1.3-1.9) and crotamiton (1.1-1.6) in the sludge samples are also determined in this study. These findings indicate the limitations of current sewage treatment techniques for the removal of these water-soluble drugs (i.e. DEET, carbamazepine, and crotamiton).

  8. Mechanobiology of embryonic limb development.

    Science.gov (United States)

    Nowlan, Niamh C; Murphy, Paula; Prendergast, Patrick J

    2007-04-01

    Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo, particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: (a) experimental alteration of the mechanical environment, (b) mechanical properties of embryonic tissues, and (c) the use of computational models. Then we analyze the main issues, and suggest how experimental and computational fields could work closer together to enhance our understanding of mechanobiology of the embryonic skeleton.

  9. Biodegradation of carbamazepine using freshwater microalgae Chlamydomonas mexicana and Scenedesmus obliquus and the determination of its metabolic fate.

    Science.gov (United States)

    Xiong, Jiu-Qiang; Kurade, Mayur B; Abou-Shanab, Reda A I; Ji, Min-Kyu; Choi, Jaeyoung; Kim, Jong Oh; Jeon, Byong-Hun

    2016-04-01

    This study evaluated the toxicity and cellular stresses of carbamazepine (CBZ) on Chlamydomonas mexicana and Scenedesmus obliquus, and its biodegradation by both microalgal species. The growth of both microalgal species decreased with increase of CBZ concentration. The growth of S. obliquus was significantly inhibited (97%) at 200 mg CBZ L(-1), as compared to the control after 10days; whereas, C. mexicana showed 30% inhibition at the same experimental conditions. Biochemical characteristics including total chlorophyll, carotenoid contents and enzyme activities (SOD and CAT) for both species were affected by CBZ at relatively high concentration. C. mexicana and S. obliquus could achieve a maximum of 35% and 28% biodegradation of CBZ, respectively. Two metabolites (10,11-dihydro-10,11-expoxycarbamazepine and n-hydroxy-CBZ) were identified by UPLC-MS, as a result of CBZ biodegradation by C. mexicana. This study demonstrated that C. mexicana was more tolerant to CBZ and could be used for treatment of CBZ contaminated wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Alterations to embryonic serotonin change aggression and fearfulness

    Science.gov (United States)

    Prenatal environment, including maternal hormones, affects the development of the serotonin (5-HT) system, with long-lasting effects on mood and behavioral exhibition in children and adults. The chicken provides a unique animal model to study the effects of embryonic development on childhood and ado...

  11. Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

    2012-01-01

    It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. In a randomized double-blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8(th) and 12(th) weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity.

  12. Carbamazepine behaviour and effects in an urban wastewater MBR working with high sludge and hydraulic retention time.

    Science.gov (United States)

    González-Pérez, Daniel María; Pérez, Jorge Ignacio; Nieto, Miguel Ángel Gómez

    2016-08-23

    The behaviour and fate of carbamazepine (CBZ) in urban wastewater treatment by a membrane bioreactor (MBR) and its possible effects on the system's efficiency, and on mixed microbial communities, has been studied. The experimental microfiltration MBR system, with capacity to treat 10.8 m(3) d(-1) of urban wastewater, operated with a pre-denitrification configuration with high sludge and hydraulic retention time. The CBZ concentration assayed was higher than in the usual urban wastewater, in order to provoke a strong biomass reaction. Influent, effluent, and all bioreactors of the MBR system were analysed in order to calculate a CBZ balance. Bench-scale experiments and respirometric analyses were performed, with and without the presence of CBZ, to evaluate its influence on the bacterial activity. The respirometric assays showed variations in the oxygen uptake rate (OUR) in the presence of CBZ. Negative effects were detected in the MBR bacterial community during the initial period of dosing. However, the effects were not permanent and the biomass spiked with CBZ had behaviour similar to that of the biomass without CBZ after a few hours. Biodegradation was not detected during the MBR treatment. The system showed an inefficient elimination of CBZ (less than 10%) with a high concentration in the effluent. The small percentage of CBZ removal was associated with the sludge retention and eliminated by the purge. All CBZ present in the influent was accounted for, and even an increase in the total amount of CBZ was registered in the permeate. During and after the experimental process, CBZ did not significantly affect the efficiency of the MBR system, and the quality of the effluent was not affected by the dosing of CBZ in terms of COD and nitrogen removal.

  13. Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial

    OpenAIRE

    Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

    2012-01-01

    Background: It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus.Methods: In a randomized double–blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tin...

  14. Molecular structure and spectroscopic characterization of Carbamazepine with experimental techniques and DFT quantum chemical calculations

    Science.gov (United States)

    Suhasini, M.; Sailatha, E.; Gunasekaran, S.; Ramkumaar, G. R.

    2015-04-01

    A systematic vibrational spectroscopic assignment and analysis of Carbamazepine has been carried out by using FT-IR, FT-Raman and UV spectral data. The vibrational analysis were aided by electronic structure calculations - ab initio (RHF) and hybrid density functional methods (B3LYP) performed with standard basis set 6-31G(d,p). Molecular equilibrium geometries, electronic energies, natural bond order analysis, harmonic vibrational frequencies and IR intensities have been computed. A detailed interpretation of the vibrational spectra of the molecule has been made on the basis of the calculated Potential Energy Distribution (PED) by VEDA program. UV-visible spectrum of the compound was also recorded and the electronic properties, such as HOMO and LUMO energies and λmax were determined by HF/6-311++G(d,p) Time-Dependent method. The thermodynamic functions of the title molecule were also performed using the RHF and DFT methods. The restricted Hartree-Fock and density functional theory-based nuclear magnetic resonance (NMR) calculation procedure was also performed, and it was used for assigning the 13C and 1H NMR chemical shifts of Carbamazepine.

  15. Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions

    Directory of Open Access Journals (Sweden)

    Mônia Aparecida Lemos Pinto

    2014-12-01

    Full Text Available Carbamazepine (CBZ, a widely used anticonvulsant drug, can crystallize and exhibits four polymorphic forms and one dihydrate. Anhydrous CBZ can spontaneously absorb water and convert to the hydrate form whose different crystallinity leads to lower biological activity. The present study was concerned to the possibility of recovering the hydrated form by heating. The thermal behavior of spontaneously hydrated carbamazepine was investigated by TG/DTG-DTA and DSC in dynamic atmospheres of air and nitrogen, which revealed that the spontaneous hydration of this pharmaceutical resulted in a Form III hydrate with 1.5 water molecules. After dehydration, this anhydrous Form III converted to Form I, which melted and decomposed in a single event, releasing isocyanic acid, as shown by evolved gas analysis using TG-FTIR. Differential scanning calorimetry analyses revealed that Form III melted and crystallized as Form I, and that subsequent cooling cycles only generated Form I by crystallization. Solid state decomposition kinetic studies showed that there was no change in the substance after the elimination of water by heating to 120 °C. Activation energies of 98 ± 2 and 93 ± 2 kJ mol-1 were found for the hydrated and dried samples, respectively, and similar profiles of activation energy as a function of conversion factor were observed for these samples.

  16. [Utilization of carbamazepine and oxcarbazepine in pediatric patients with partial epilepsy in Spain. An observational study].

    Science.gov (United States)

    Rufo Campos, M; Carreño, M

    2009-01-01

    It is important to conduct studies on the utilization of new antiepileptic drugs in order to improve their use. Our objective is to describe the use patterns of carbamazepine and oxcarbazepine. Observational, cross-sectional, national study with 58 investigators that included 185 pediatric patients with partial epilepsy. We recorded prescription patterns, quality of life (QoL) using the QoL scale in childhood epilepsy (CAVE) and use of resources. 134 patients were under treatment with oxcarbazepine (72.4 %), with a mean dose of 22.3 mg/kg/day; standard deviation (SD): 8.04; 95 % confidence interval (CI): 20.9 to 23.7, and 51 (27.6%) with carbamazepine, mean dose of 14 mg/kg/day; SD: 6.2; 95 % CI: 12.3 to 15.8. A total of 19.4% and 21.6 %, respectively, followed multiple drug treatment. The mean scores on functional dimensions of CAVE were (out of 5): school attendance: 4.5; SD: 0.7; social relationships: 4.1; SD: 0.9, and autonomy: 3.9; SD: 1.9. Patients receiving multiple drug therapy had worse results in quality of life (p used in lower doses than recommended and the dosing is not adjusted for weight. Underdosing may lead to regimes of multiple drug therapy that should be reviewed individually.

  17. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    Directory of Open Access Journals (Sweden)

    Okujava Michael

    2001-11-01

    Full Text Available Abstract Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry influences the blood oxygenation level dependent (BOLD contrast changes induced by neuronal activation and measured by functional MRI (fMRI. We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE. Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

  18. Metabolite profiling of carbamazepine and ibuprofen in Solea senegalensis bile using high-resolution mass spectrometry.

    Science.gov (United States)

    Aceña, Jaume; Pérez, Sandra; Eichhorn, Peter; Solé, Montserrat; Barceló, Damià

    2017-09-01

    The widespread occurrence of pharmaceuticals in the aquatic environment has raised concerns about potential adverse effects on exposed wildlife. Very little is currently known on exposure levels and clearance mechanisms of drugs in marine fish. Within this context, our research was focused on the identification of main metabolic reactions, generated metabolites, and caused effects after exposure of fish to carbamazepine (CBZ) and ibuprofen (IBU). To this end, juveniles of Solea senegalensis acclimated to two temperature regimes of 15 and 20 °C for 60 days received a single intraperitoneal dose of these drugs. A control group was administered the vehicle (sunflower oil). Bile samples were analyzed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry on a Q Exactive (Orbitrap) system, allowing to propose plausible identities for 11 metabolites of CBZ and 13 metabolites of IBU in fish bile. In case of CBZ metabolites originated from aromatic and benzylic hydroxylation, epoxidation, and ensuing O-glucuronidation, O-methylation of a catechol-like metabolite was also postulated. Ibuprofen, in turn, formed multiple hydroxyl metabolites, O-glucuronides, and (hydroxyl)-acyl glucuronides, in addition to several taurine conjugates. Enzymatic responses after drug exposures revealed a water temperature-dependent induction of microsomal carboxylesterases. The metabolite profiling in fish bile provides an important tool for pharmaceutical exposure assessment. Graphical abstract Studies of metabolism of carbamazepine and ibuprofen in fish.

  19. Generation of 1:1 Carbamazepine:Nicotinamide cocrystals by spray drying.

    Science.gov (United States)

    Patil, Shashank P; Modi, Sameer R; Bansal, Arvind K

    2014-10-01

    The present study investigates the potential of spray drying as a technique for generation of pharmaceutical cocrystals. Carbamazepine-Nicotinamide cocrystal (CNC) was chosen as model cocrystal system for this study. Firstly, CNC was generated using liquid assisted grinding and used for generation of phase solubility diagram (PSD) and ternary phase diagram (TPD). Both PSD and TPD were carefully evaluated for phase behavior of CNC when equilibrated with solvent. The undersaturated region with respect to CNC, as depicted by TPD, was selected as target region to initiate cocrystallization experiments. Various points in this region, representative of different compositions of Carbamazepine, Nicotinamide and CNC, were selected and spray drying was carried out. The spray dried product was characterized for solid state properties and was compared with CNC generated by liquid assisted grinding. Spray drying successfully generated CNC of similar quality as those generated by liquid assisted grinding. Moreover, there was no significant impact of process variables on formation of CNC. Spray drying, owing to its simplicity and industrial scalability, can be a promising method for large scale cocrystal generation. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Analytical method by high resolution liquid chromatography for the determination of carbamazepine in human plasma

    International Nuclear Information System (INIS)

    Jimenez Aleman, Narda M; Calero Carbonell, Jorge E; Padron Yaquis, Alejandro S; Izquierdo Lozano, Julio C

    2007-01-01

    One of the requirements to develop the studies of bioavailability and bioequivalence is to have analytic methodologies validated for the work with samples in biological fluids. A method was developed by high resolution liquid chromatography for the determination of carbamazepine in human plasma. A mixture of hydrogen phosphate of sodium: acetonitrile (65:35) adjusted to pH= 3.3 with phosphoric acid, flow of 1.2 mL/min and ultraviolet detection at 210 nm, was used as mobile phase. Propylparabene was used as an internal standard. According to the established regulations for the validation of the methods in biological fluids, the following parameters were studied: stability of the samples, lineality, specificity, precision, accuracy and limit of detection and quantification. The method proved to be specific and sensitive with a detection and quantification limit of 0.9 and 1.0 ng, respectively. The method was lineal, precise and exact in the range of concentrations of 1. 07 at 12.67 μg/mL. The mean recovery was not statistically different from 100.0 %. The analito in the proposed biological matrix remained in the studied period. The methodology described in this work is applied in our case to the study that evaluates the bioavailability and bioequivalence of a Cuban formulation of carbamazepine in healthy volunteers. (Author)

  1. Somatic donor cell type correlates with embryonic, but not extra-embryonic, gene expression in postimplantation cloned embryos.

    Directory of Open Access Journals (Sweden)

    Ryutaro Hirasawa

    Full Text Available The great majority of embryos generated by somatic cell nuclear transfer (SCNT display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts. The embryos retrieved from the uteri were separated into embryonic (epiblast and extraembryonic (extraembryonic ectoderm and ectoplacental cone tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs (>2-fold vs. controls than did the extraembryonic tissues (P<1.0 × 10(-26. In the embryonic tissues, one of the common abnormalities was upregulation of Dlk1, a paternally imprinted gene. This might be a potential cause of the occasional placenta-only conceptuses seen in SCNT-generated mouse embryos (1-5% per embryos transferred in our laboratory, because dysregulation of the same gene is known to cause developmental failure of embryos derived from induced pluripotent stem cells. There were also some DEGs in the extraembryonic tissues, which might explain the poor development of SCNT-derived placentas at early stages. These findings suggest that SCNT affects the embryonic and extraembryonic development differentially and might cause further deterioration in the embryonic lineage in a donor cell-specific manner. This could explain donor cell-dependent variations in cloning efficiency using SCNT.

  2. The use of quantum chemistry in pharmaceutical research as illustrated by case studies of indometacin and carbamazepine

    DEFF Research Database (Denmark)

    Gordon, Keith C; McGoverin, Cushla M; Strachan, Clare J

    2007-01-01

    A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed...

  3. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4

    DEFF Research Database (Denmark)

    Andreasen, Astrid-Helene; Brøsen, Kim; Damkier, Per

    2007-01-01

    PURPOSE: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. We...

  4. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    Science.gov (United States)

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

  5. Low oxygen levels slow embryonic development of Limulus polyphemus

    DEFF Research Database (Denmark)

    Funch, Peter; Wang, Tobias; Pertoldi, Cino

    2016-01-01

    The American horseshoe crab Limulus polyphemus typically spawns in the upper intertidal zone, where the developing embryos are exposed to large variations in abiotic factors such as temperature, humidity, salinity, and oxygen, which affect the rate of development. It has been shown that embryonic...... pronounced hypoxia in later embryonic developmental stages, but also in earlier, previously unexplored, developmental stages....... development is slowed at both high and low salinities and temperatures, and that late embryos close to hatching tolerate periodic hypoxia. In this study we investigated the influence of hypoxia on both early and late embryonic development in L. polyphemus under controlled laboratory conditions. Embryos were...

  6. Effects of Pulsed Electromagnetic Field on Differentiation of HUES-17 Human Embryonic Stem Cell Line

    Directory of Open Access Journals (Sweden)

    Yi-Lin Wu

    2014-08-01

    Full Text Available Electromagnetic fields are considered to potentially affect embryonic development, but the mechanism is still unknown. In this study, human embryonic stem cell (hESC line HUES-17 was applied to explore the mechanism of exposure on embryonic development to pulsed electromagnetic field (PEMF for 400 pulses at different electric field intensities and the differentiation of HUES-17 cells was observed after PEMF exposure. The expression of alkaline phosphatase (AP, stage-specific embryonic antigen-3 (SSEA-3, SSEA-4 and the mRNA level and protein level of Oct4, Sox2 and Nanog in HUES-17 cells remained unchanged after PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m. Four hundred pulses PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m did not affect the differentiation of HUES-17 cells. The reason why electromagnetic fields affect embryonic development may be due to other mechanisms rather than affecting the differentiation of embryonic stem cells.

  7. Do carbamazepine, gabapentin, or other anticonvulsants exert sufficient radioprotective effects to alter responses from trigeminal neuralgia radiosurgery?

    Science.gov (United States)

    Flickinger, John C; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S; Arai, Yoshio; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas; Flickinger, John C

    2012-07-15

    Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age ≤70 years, and Type 1 typical

  8. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  9. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    International Nuclear Information System (INIS)

    Flickinger, John C.; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S.; Arai, Yoshio; Niranjan, Ajay; Lunsford, L. Dade; Kondziolka, Douglas; Flickinger, John C.

    2012-01-01

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6–153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with

  10. Application of experimental design in examination of the dissolution rate of carbamazepine from formulations: Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

    Directory of Open Access Journals (Sweden)

    Krstić Marko

    2015-01-01

    Full Text Available Poor solubility is one of the key reasons for the poor bioavailability of these drugs. This paper displays a formulation of a solid surfactant system with carbamazepine, in order to increase its dissolution rate. Solid state surfactant systems are formed by application of fractal experimental design. Poloxamer 237 and Poloxamer 338 were used as surfactants and Brij® 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite and a synthetic adsorbent carrier (Neusiline UFL2 on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influence of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR, PXRD. It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions. [Projekat Ministarstva nauke Republike Srbije, br. TR34007

  11. How the embryonic chick brain twists

    OpenAIRE

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A.

    2016-01-01

    During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left–right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic m...

  12. Epidemiology, pathophysiology and putative genetic basis of carbamazepine- and oxcarbazepine-induced hyponatremia.

    Science.gov (United States)

    Berghuis, B; de Haan, G-J; van den Broek, M P H; Sander, J W; Lindhout, D; Koeleman, B P C

    2016-09-01

    The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ- and OXC-induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway. © 2016 EAN.

  13. Removal of carbamazepine and clofibric acid from water using double templates-molecularly imprinted polymers.

    Science.gov (United States)

    Dai, Chao-meng; Zhang, Juan; Zhang, Ya-lei; Zhou, Xue-fei; Duan, Yan-ping; Liu, Shu-guang

    2013-08-01

    A novel double templates-molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using carbamazepine (CBZ) and clofibric acid (CA) as the double templates molecular and 2-vinylpyridine as functional monomer. The equilibrium data of MIP was well described by the Freundlich isotherm model. Two kinetic models were adopted to describe the experimental data, and the pseudo second-order model well-described adsorption of CBZ and CA on the MIP. Adsorption experimental results showed that the MIP had good selectivity and adsorption capacity for CBZ and CA in the presence of competitive compounds compared with non-imprinted polymer, commercial powdered activated carbon, and C18 adsorbents. The feasibility of removing CBZ and CA from water by the MIP was demonstrated using tap water, lake water, and river water.

  14. Spray Drying as a Reliable Route to Produce Metastable Carbamazepine Form IV.

    Science.gov (United States)

    Halliwell, Rebecca A; Bhardwaj, Rajni M; Brown, Cameron J; Briggs, Naomi E B; Dunn, Jaclyn; Robertson, John; Nordon, Alison; Florence, Alastair J

    2017-07-01

    Carbamazepine (CBZ) is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least 5 polymorphic forms. Metastable form IV was originally discovered from crystallization with polymer additives; however, it has not been observed from subsequent solvent-only crystallization efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic CBZ solution. Characterization of the material was carried out using diffraction, scanning electron microscopy, and differential scanning calorimetry. In situ Raman spectroscopy was used to monitor the spray-dried product during the spray drying process. This work demonstrates that spray drying provides a robust method for the production of form IV CBZ, and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallization approaches to produce metastable crystalline forms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Photochemical degradation of atenolol, carbamazepine, meprobamate, phenytoin and primidone in wastewater effluents

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Mei Mei [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States); Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Trenholm, Rebecca [Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Rosario-Ortiz, Fernando L., E-mail: Fernando.rosario@colorado.edu [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States)

    2015-01-23

    Highlights: • The photochemical degradation of 5 compounds was evaluated in wastewater effluents. • Attenuation by sensitized photolysis was the most important degradation pathway. • Hydroxyl radical accounted for most of the degradation for aliphatic compounds. • Other transient oxidants could also significantly impact the degradation of the compounds. - Abstract: The photochemical degradation of five pharmaceuticals was examined in two secondary wastewater effluents. The compounds, which included atenolol, carbamazepine, meprobamate, phenytoin and primidone, were evaluated for both direct and sensitized photolysis. In the two wastewaters, direct photolysis did not lead to significant compound degradation; however, sensitized photolysis was an important removal pathway for the five pharmaceuticals. Upon solar irradiation, hydroxyl radical (HO·) was quantified using the hydroxylation of benzene and singlet oxygen ({sup 1}O{sub 2}) formation was monitored following the degradation of furfuryl alcohol. Degradation via sensitized photolysis was observed following five-day exposures for atenolol (69–91%), carbamazepine (67–98%), meprobamate (16–52%), phenytoin (44–85%), and primidone (34–88%). Varying removal is likely a result of the differences in reactivity with transient oxidants. Averaged steady state HO· concentrations ranged from 1.2 to 4.0 × 10{sup −16} M, whereas the concentrations of {sup 1}O{sub 2} were 6.0–7.6 × 10{sup −14} M. Partial removal due to presence of HO· indicates it was not the major sink for most compounds examined. Other transient oxidants, such as {sup 1}O{sub 2} and triplet state effluent organic matter, are likely to play important roles in fates of these compounds.

  16. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  17. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  18. Vertebrate Embryonic Cleavage Pattern Determination.

    Science.gov (United States)

    Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco

    2017-01-01

    The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.

  19. Anhydrate to hydrate solid-state transformations of carbamazepine and nitrofurantoin in biorelevant media studied in situ using time-resolved synchrotron X-ray diffraction

    DEFF Research Database (Denmark)

    Bøtker, Johan Peter; Rantanen, Jukka; Arnfast, Lærke

    2016-01-01

    with different biorelevant media, simulated fasted and fed state intestinal fluids containing bile salt and dioleoylphosphatidylcholine (DOPC) micelles, DOPC/sodium dodecyl sulfate (SDS) mixture, bile salt solution and water. Two anhydrate compounds (carbamazepine, CBZ and nitrofurantoin, NF) with different...

  20. Application of experimental design in examination of the dissolution rate of carbamazepine from formulations: Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

    OpenAIRE

    Krstić Marko; Ražić Slavica; Vasiljević Dragana; Spasojević Đurđija; Ibrić Svetlana

    2015-01-01

    Poor solubility is one of the key reasons for the poor bioavailability of these drugs. This paper displays a formulation of a solid surfactant system with carbamazepine, in order to increase its dissolution rate. Solid state surfactant systems are formed by application of fractal experimental design. Poloxamer 237 and Poloxamer 338 were used as surfactants and Brij® 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied...

  1. The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

    2006-11-01

    In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

  2. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  3. [Embryonic stem cells. Future perspectives].

    Science.gov (United States)

    Groebner, M; David, R; Franz, W M

    2006-05-01

    Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

  4. Maternal Embryonic Leucine Zipper Kinase (MELK: A Novel Regulator in Cell Cycle Control, Embryonic Development, and Cancer

    Directory of Open Access Journals (Sweden)

    Pengfei Jiang

    2013-10-01

    Full Text Available Maternal embryonic leucine zipper kinase (MELK functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis. In these cellular processes, MELK functions by binding to numerous proteins. In general, the effects of multiple protein interactions with MELK are oncogenic in nature, and the overexpression of MELK in kinds of cancer provides some evidence that it may be involved in tumorigenic process. In this review, our current knowledge of MELK function and recent discoveries in MELK signaling pathway were discussed. The regulation of MELK in cancers and its potential as a therapeutic target were also described.

  5. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine

    OpenAIRE

    Krstić Marko Z.; Ibrić Svetlana R.

    2016-01-01

    One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol® (1:...

  6. Chemometrics enhanced HPLC-DAD performance for rapid quantification of carbamazepine and phenobarbital in human serum samples.

    Science.gov (United States)

    Vosough, Maryam; Ghafghazi, Shiva; Sabetkasaei, Masoumeh

    2014-02-01

    This paper describes development and validation of a simple and efficient bioanalytical procedure for simultaneous determination of phenobarbital and carbamazepine in human serum samples using high performance liquid chromatography with photodiode-array detection (HPLC-DAD) regarding a fast elution methodology in less than 5 min. Briefly, this method consisted of a simple deproteinization step of serum samples followed by HPLC analysis on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH=7.5) buffer solution (45:55). Due to the presence of serum endogenous components as non-calibrated components in the sample, second-order calibration based on multivariate curve resolution-alternating least squares (MCR-ALS), has been applied on a set of absorbance matrices collected as a function of retention time and wavelengths. Acceptable resolution and quantification results were achieved in the presence of matrix interferences and the second-order advantage was fully exploited. The average recoveries for carbamazepine and phenobarbital were 89.7% and 86.1% and relative standard deviation values were lower than 9%. Additionally, computed elliptical joint confidence region (EJCR) confirmed the accuracy of the proposed method and indicated the absence of both constant and proportional errors in the predicted concentrations. The developed method enabled the determination of the analytes in different serum samples in the presence of overlapped profiles, while keeping experimental time and extraction steps at minimum. Finally, the serum concentration levels of carbamazepine in three time intervals were reported for morphine-dependents who had received carbamazepine for treating their neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

  7. Sensory abnormalities and masticatory function after microvascular decompression or balloon compression for trigeminal neuralgia compared with carbamazepine and healthy controls.

    Science.gov (United States)

    Ichida, Michelle Cristina; de Almeida, Antonio Nogueira; da Nobrega, Jose Claudio Marinho; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu Tesseroli; de Siqueira, Silvia R D T

    2015-06-01

    Idiopathic trigeminal neuralgia (iTN) is a neurological condition treated with pharmacotherapy or neurosurgery. There is a lack of comparative papers regarding the outcomes of neurosurgery in patients with iTN. The objective of this study was to investigate sensory thresholds and masticatory function in 78 patients with iTN who underwent microvascular decompression (MVD) or balloon compression (BC), and compare these treatments with carbamazepine and 30 untreated healthy controls. The authors conducted a case-controlled longitudinal study. Patients were referred to 1 of 3 groups: MVD, BC, or carbamazepine. All patients were evaluated before and after treatment with a systematic protocol composed of a clinical orofacial questionnaire, Research Diagnostic Criteria for temporomandibular disorders, Helkimo indices, and a quantitative sensory-testing protocol (gustative, olfactory, cold, warm, touch, vibration, superficial, and deep pain thresholds). Both MVD and BC were effective at reducing pain intensity (p = 0.012) and carbamazepine doses (p sweet (p = 0.014) and salty (p = 0.003) thresholds. The sour threshold decreased (p = 0.003) and cold and warm thresholds increased (p sensorial and motor deficits after BC need to be included as targets directly associated with the success of the surgery and need to be assessed and relieved as goals in the treatment of iTN.

  8. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    Science.gov (United States)

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  9. Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio).

    Science.gov (United States)

    Triebskorn, R; Casper, H; Scheil, V; Schwaiger, J

    2007-02-01

    In order to assess potential effects of human pharmaceuticals in aquatic wildlife, laboratory experiments were conducted with carbamazepine, clofibric acid, metoprolol, and diclofenac using fish as test organisms. For each substance, at least one environmentally relevant concentration was tested. In liver, kidney, and gills of trout and carp exposed to carbamazepine, clofibric acid, and metoprolol, ultrastructural effects were qualitatively described and semi-quantitatively assessed. The obtained assessment values were compared with previously published data for diclofenac-induced effects in rainbow trout tissues. Quantitative analyses of protein accumulated in kidneys of diclofenac-exposed trout corroborated previously published data which indicated that diclofenac induced a severe glomerulonephritis resulting in a hyaline droplet degeneration of proximal kidney tubules. The investigations provided information on the general health status of the pharmaceutical-exposed fish, and allowed a differential diagnosis of harmful effects caused by these human pharmaceuticals in non-target species. For the different cytological effects observed, lowest observed effect concentration (LOECs) for at least three of the test substances (diclofenac, carbamazepine, metoprolol) were in the range of environmentally relevant concentrations (1 microg/L).

  10. A new herb–drug interaction of Polygonum cuspidatum, a resveratrol‐rich nutraceutical, with carbamazepine in rats

    International Nuclear Information System (INIS)

    Chi, Ying-Chang; Lin, Shiuan-Pey; Hou, Yu-Chi

    2012-01-01

    Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE), an active metabolite. This study investigated the acute and chronic effects of Polygonum cuspidatum (PC), a resveratrol‐rich nutraceutical, on the pharmacokinetics of CBZ in rats and the underlying mechanisms. Rats were orally administered CBZ (200 mg/kg) alone and coadministered with a single dose and the 7th dose of PC (2 g/kg) in a crossover design. The concentrations of CBZ and CBZE in serum and various tissues were determined by HPLC method. The results showed that PC significantly increased the AUC 0-t of CBZ and CBZE, whereas the formation rate of CBZE was decreased. Tissue analysis showed that the concentrations of CBZ and CBZE in brain, liver and kidney were significantly increased by PC. Cell studies indicated that the efflux function of MRP 2 was inhibited by the serum metabolites of PC. In conclusion, PC markedly increased the systemic exposure and brain concentration of CBZ and CBZE through inhibiting the activities of CYP 3A and MRP 2. Highlights: ► Polygonum cuspidatum elevated brain carbamazepine (CBZ) levels. ► Polygonum cuspidatum inhibited the activities of CYP 3A and MRP 2. ► Coadministration of PC with CBZ may enhance efficacy or toxicity.

  11. A new herb–drug interaction of Polygonum cuspidatum, a resveratrol‐rich nutraceutical, with carbamazepine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Ying-Chang [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, 40402, Taiwan (China); Lin, Shiuan-Pey [School of Pharmacy, China Medical University, Taichung, 40402, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, 40402, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan (China)

    2012-09-15

    Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE), an active metabolite. This study investigated the acute and chronic effects of Polygonum cuspidatum (PC), a resveratrol‐rich nutraceutical, on the pharmacokinetics of CBZ in rats and the underlying mechanisms. Rats were orally administered CBZ (200 mg/kg) alone and coadministered with a single dose and the 7th dose of PC (2 g/kg) in a crossover design. The concentrations of CBZ and CBZE in serum and various tissues were determined by HPLC method. The results showed that PC significantly increased the AUC{sub 0-t} of CBZ and CBZE, whereas the formation rate of CBZE was decreased. Tissue analysis showed that the concentrations of CBZ and CBZE in brain, liver and kidney were significantly increased by PC. Cell studies indicated that the efflux function of MRP 2 was inhibited by the serum metabolites of PC. In conclusion, PC markedly increased the systemic exposure and brain concentration of CBZ and CBZE through inhibiting the activities of CYP 3A and MRP 2. Highlights: ► Polygonum cuspidatum elevated brain carbamazepine (CBZ) levels. ► Polygonum cuspidatum inhibited the activities of CYP 3A and MRP 2. ► Coadministration of PC with CBZ may enhance efficacy or toxicity.

  12. Sorption of carbamazepine by commercial graphene oxides: a comparative study with granular activated carbon and multiwalled carbon nanotubes.

    Science.gov (United States)

    Cai, Nan; Larese-Casanova, Philip

    2014-07-15

    Graphene nanosheet materials represent a potentially new high surface area sorbent for the treatment of endocrine disrupting compounds (EDCs) in water. However, sorption behavior has been reported only for laboratory graphene prepared by a laborious and hazardous graphite exfoliation process. A careful examination of commercially available, clean, high-volume produced graphene materials should reveal whether they are appropriate for sorbent technologies and which physicochemical properties most influence sorption performance. In this study, three commercially available graphene oxide powders of various particle sizes, specific surface areas, and surface chemistries were evaluated for their sorption performance using carbamazepine and nine other EDCs and were compared to that of conventional granular activated carbon (GAC) and multi-walled carbon nanotubes (MWCNTs). Sorption kinetics of carbamazepine on graphene oxide powders was rapid and reversible with alcohol washing, consistent with π-π interactions. The various sorption extents as described by Freundlich isotherms were best explained by available surface area, and only the highest surface area graphene oxide (771 m(2)/g) out-performed GAC and MWCNTs. Increasing pH caused more negative surface charge, a twofold decrease in sorption of anionic ibuprofen, a onefold increase in sorption of cationic atenolol, and no change for neutral carbamazepine, highlighting the role of electrostatic interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia

    Directory of Open Access Journals (Sweden)

    Xue H

    2018-04-01

    Full Text Available Hui Xue,1,2 Wenping Xiang,2 Yichuan Yu,3 Guorong Liu,2 Yi Chong,2 Jiying Zhou1 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Neurology, Baotou Central Hospital, Inner Mongolia, Baotou, China; 3Department of Emergency, Yongchuan Hospital of Chongqing Medical University, Chongqing, China Background: Vestibular paroxysmia (VP is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ plus betahistine mesilate tablets (BMT (CBZ+BMT and oxcarbazepine (OXC plus BMT (OXC+BMT in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT.Methods: VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed.Results: In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group (p=0.04. Subgroup analysis found that patients receiving BMT (18 mg had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg.Conclusion: These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ

  14. DIFFERENTIATION OF EMBRYONIC STEM CELLS: LESSONS FROM EMBRYONIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    EMOKE PALL

    2008-05-01

    Full Text Available Embryonic stem (ES cells, the undifferentiated cells of early embryos are established as permanent lines and are characterised by their self-renewal capacity and the ability to retain their developmental capacity in vivo and in vitro. The pluripotent properties of ES cells are the basis of gene targeting technologies used to create mutant mouse strains with inactivated genes by homologous recombination. There are several methods to induce the formation of EBs. One of them the formation by aggregating ES cells in hanging drops, using gravity as an aggregation force. This method presents the advantage of obtaining well-calibrated EBs almost identical in size. We used at our experiment the mouse ES cell line KA1/11/C3/C8 with a normal karyotype, at 14th passages. Immunohistochemical examination was aimed to identify tissue-restricted proteins for the two differentiated lineages: titin as a cell-specific antigen for cardiac and skeletal muscle, betaIII-tubulin for the neuronal differentiation, cytokeratin Endo-A (TROMA for the presence of mesenchymal progenitor cells, Oct-4 for the presence of the undifferentiated ES cells. The beating cardiac muscle clumps showed more synchronous rhythm than those seen in EBs obtained from suspension culture method, where the beating cardiac muscle clumps appeared later, had a lower frequency and were uneven. The synaptic networks of neuronal cells were best developed in EBs from suspension, compared to those observed in EBs from hanging-drop method.

  15. Effects of pharmaceutical micropollutants on the membrane fouling of a submerged MBR treating municipal wastewater: case of continuous pollution by carbamazepine.

    Science.gov (United States)

    Li, Chengcheng; Cabassud, Corinne; Reboul, Bernard; Guigui, Christelle

    2015-02-01

    Membrane bioreactor (MBR) is increasingly used for municipal wastewater treatment and reuse and great concerns have been raised to some emerging trace pollutants found in aquatic environment in the last decade, notably the pharmaceuticals. As a consequence the removal of pharmaceutical micropollutants by MBRs has been extensively investigated. But there is still a lack of knowledge on the effects of the current presence of pharmaceutical micropollutants in domestic wastewaters on MBR fouling. Among the different pharmaceuticals, it was decided to focus on carbamazepine (CBZ), an anti-epileptic drug, because of its occurrence in domestic wastewaters and persistency in biological processes including MBRs. This paper focuses on the effects of continuous carbamazepine pollution on MBR fouling. A continuous introduction of CBZ into the MBR via the feed (about 90 μg L(-1) CBZ in the feed) provoked a TMP jump. It occurred just 1 day after the addition of CBZ in MBR and a significantly higher increase rate of TMP was also observed after 1 day after addition of CBZ in MBR, as compared to that before addition of CBZ. This indicates that the pharmaceutical stress induced by CBZ causes more severe membrane fouling. Addition of CBZ was shown to induce a significant increase of the concentration of proteins in the supernatant at the beginning several days then stabilized to original level whereas no significant change was found for polysaccharides. HPLC-SEC analysis showed that addition of CBZ induced a decrease of 100-1000 kDa protein-like SMPs and a more significant increase of 10-100 kDa protein-like SMPs in the supernatant. Moreover it was found that addition of CBZ in the MBR affected the sludge microbial activities, as a slight inhibition (about 20%) of the exogenous respiration rate was observed. The increased membrane fouling could be related to the change in biomass characteristics and supernatant quality after addition of CBZ in MBR. This study allows also

  16. Microglia Modulate Wiring of the Embryonic Forebrain

    Directory of Open Access Journals (Sweden)

    Paola Squarzoni

    2014-09-01

    Full Text Available Dysfunction of microglia, the tissue macrophages of the brain, has been associated with the etiology of several neuropsychiatric disorders. Consistently, microglia have been shown to regulate neurogenesis and synaptic maturation at perinatal and postnatal stages. However, microglia invade the brain during mid-embryogenesis and thus could play an earlier prenatal role. Here, we show that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits. Using multiple mouse models, including cell-depletion approaches and cx3cr1−/−, CR3−/−, and DAP12−/− mutants, we find that perturbing microglial activity affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons. Since defects in both dopamine innervation and cortical networks have been linked to neuropsychiatric diseases, our study provides insights into how microglial dysfunction can impact forebrain connectivity and reveals roles for immune cells during normal assembly of brain circuits.

  17. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine

    Directory of Open Access Journals (Sweden)

    Krstić Marko Z.

    2016-01-01

    Full Text Available One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS. Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS consisting of oil phase (caprilic-capric triglycerides, a surfactant (Polisorbat 80 and Labrasol® (1:1 and cosurfactant (Transcutol® HP are formed by applying mixture design. 16 formulations were formulated, where proportion of lipids, surfactant and cosurfactant were varied (input parameters in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water, the droplet size and polydispersity index (PdI of the obtained emulsions (output parameters were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin® UFl2, Neusilin® FL2, Sylysia® 320, diatomite were used as the carriers. The ratio of SNEDDS:carrier varied (1:1, 2:1. Dissolution testing was carried out in the rotation paddles apparatus. Caracterization of solid SNEDDS was performed using the hot stage microscopy (HSM, thermogravimetric analysis (TGA, differential scanning calorimetry (DSC, infrared spectrophotometry with Fourier transformation (FT-IR, scanning electron microscopy (SEM and X-ray diffraction (PXRD. Selected SNEDDS consisting of lipids (21.12%, surfactant (42.24% and cosurfactant (36.64% had a droplet size 157.02±34.09 nm and PDI 0.184±0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia® 320. It can be concluded that in all

  18. Thermodynamic Solubility Profile of Carbamazepine-Cinnamic Acid Cocrystal at Different pH.

    Science.gov (United States)

    Keramatnia, Fatemeh; Shayanfar, Ali; Jouyban, Abolghasem

    2015-08-01

    Pharmaceutical cocrystal formation is a direct way to dramatically influence physicochemical properties of drug substances, especially their solubility and dissolution rate. Because of their instability in the solution, thermodynamic solubility of cocrystals could not be determined in the common way like other compounds; therefore, the thermodynamic solubility is calculated through concentration of their components in the eutectic point. The objective of this study is to investigate the effect of an ionizable coformer in cocrystal with a nonionizable drug at different pH. Carbamazepine (CBZ), a nonionizable drug with cinnamic acid (CIN), which is an acidic coformer, was selected to prepare CBZ-CIN cocrystal and its thermodynamic solubility was studied in pH range 2-7. Instead of HPLC that is a costly and time-consuming method, a chemometric-based approach, net analyte signal standard addition method, was selected for simultaneous determination of CBZ and CIN in solution. The result showed that, as pH increases, CIN ionization leads to change in CBZ-CIN cocrystal solubility and stability in solution. In addition, the results of this study indicated that there is no significant difference between intrinsic solubility of CBZ and cocrystal despite the higher ideal solubility of cocrystal. This verifies that ideal solubility is not good parameter to predict cocrystal solubility. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. Metabolism of carbamazepine in plant roots and endophytic rhizobacteria isolated from Phragmites australis.

    Science.gov (United States)

    Sauvêtre, Andrés; May, Robert; Harpaintner, Rudolf; Poschenrieder, Charlotte; Schröder, Peter

    2018-01-15

    Carbamazepine (CBZ) is a pharmaceutical frequently categorized as a recalcitrant pollutant in the aquatic environment. Endophytic bacteria previously isolated from reed plants have shown the ability to promote growth of their host and to contribute to CBZ metabolism. In this work, a horseradish (Armoracia rusticana) hairy root (HR) culture has been used as a plant model to study the interactions between roots and endophytic bacteria in response to CBZ exposure. HRs could remove up to 5% of the initial CBZ concentration when they were grown in spiked Murashige and Skoog (MS) medium. Higher removal rates were observed when HRs were inoculated with the endophytic bacteria Rhizobium radiobacter (21%) and Diaphorobacter nitroreducens (10%). Transformation products resulting from CBZ degradation were identified using liquid chromatography-ultra high-resolution quadrupole time of flight mass spectrometry (LC-UHR-QTOF-MS). CBZ metabolism could be divided in four pathways. Metabolites involving GSH conjugation and 2,3-dihydroxylation, as well as acridine related compounds are described in plants for the first time. This study presents strong evidence that xenobiotic metabolism and degradation pathways in plants can be modulated by the interaction with their endophytic community. Hence it points to plausible applications for the elimination of recalcitrant compounds such as CBZ from wastewater in CWs. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Carbamazepine and oxcarbazepine in adult patients with Dravet syndrome: Friend or foe?

    Science.gov (United States)

    Snoeijen-Schouwenaars, F M; Veendrick, M J B M; van Mierlo, P; van Erp, G; de Louw, A J A; Kleine, B U; Schelhaas, H J; Tan, I Y

    2015-07-01

    In newly diagnosed patients with Dravet syndrome sodium channel blockers are usually avoided. However, in many adult patients the diagnosis was made long after the initiation of therapy. The purpose of our study was to acquire information concerning the potential risks and benefits of (ox)carba(ma)zepine withdrawal in adult patients with genetically confirmed Dravet syndrome. We identified 16 adults with Dravet syndrome, living in a tertiary care facility for people with epilepsy and an intellectual disability. We reviewed clinical history, genetic findings, the type and duration of sodium channels blockers that were used, seizure types and frequency, and the effect of a change in these medications. The study population consisted of 9 men and 7 women. Median age was 35 years (range 20-61 years). An attempt to withdraw carbamazepine (CBZ) was made in 9 patients. In 3 of these patients an increase in tonic-clonic seizures was observed. An attempt to withdraw oxcarbazepine (OXC) was made in 3 patients, leading to a complete stop in 2 patients. 3 of the 4 deaths in the withdrawal-group were related to epilepsy. In adult patients with Dravet syndrome withdrawal of CBZ or OXC is not without risks. We suggest that (ox)carba(ma)zepine withdrawal should be considered in these patients but only if there is a good reason to do so and only if they are closely monitored. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. N-Doped TiO₂-Coated Ceramic Membrane for Carbamazepine Degradation in Different Water Qualities.

    Science.gov (United States)

    Luster, Enbal; Avisar, Dror; Horovitz, Inna; Lozzi, Luca; Baker, Mark A; Grilli, Rossana; Mamane, Hadas

    2017-07-31

    The photocatalytic degradation of the model pollutant carbamazepine (CBZ) was investigated under simulated solar irradiation with an N-doped TiO₂-coated Al₂O₃ photocatalytic membrane, using different water types. The photocatalytic membrane combines photocatalysis and membrane filtration in a single step. The impact of each individual constituent such as acidity, alkalinity, dissolved organic matter (DOM), divalent cations (Mg 2+ and Ca 2+ ), and Cl - on the degradation of CBZ was examined. CBZ in water was efficiently degraded by an N-doped TiO₂-coated Al₂O₃ membrane. However, elements added to the water, which simulate the constituents of natural water, had an impact on the CBZ degradation. Water alkalinity inhibited CBZ degradation mostly due to increase in pH while radical scavenging by carbonate was more dominant at higher values (>200 mg/L as CaCO₃). A negative effect of Ca 2+ addition on photocatalytic degradation was found only in combination with phosphate buffer, probably caused by deposition of CaHPO₄ or CaHPO₄·2H₂O on the catalyst surface. The presence of Cl - and Mg 2+ ions had no effect on CBZ degradation. DOM significantly inhibited CBZ degradation for all tested background organic compounds. The photocatalytic activity of N-doped TiO₂-coated Al₂O₃ membranes gradually decreased after continuous use; however, it was successfully regenerated by 0.1% HCl chemical cleaning. Nevertheless, dissolution of metals like Al and Ti should be monitored following acid cleaning.

  2. Inhibition of the solid state transformation of carbamazepine in aqueous solution: impact of polymeric properties.

    Science.gov (United States)

    Gift, Alan D; Hettenbaugh, Jacob A; Quandahl, Rachel A; Mapes, Madison

    2017-11-06

    The effects of polymers on the anhydrate-to-hydrate transformation of carbamazepine (CBZ) was investigated. The three types of polymers studied were polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and substituted celluloses which included hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC). Anhydrous CBZ was added to dilute aqueous polymer solutions and Raman spectroscopy measurements were collected to monitor the kinetics of the solution-mediated transformation to CBZ dihydrate. Polymers exhibiting the greatest inhibition were able to reduce the growth phase of the solution-mediated transformation and change the habit of the hydrate crystal indicating polymer adsorption to the hydrate crystal surface as the mechanism of inhibition. The results of the various polymers showed that short chain substituted celluloses (HPMC and MC) inhibited the CBZ transformation to a much greater extent than longer chains. The same trend was observed for PVP and PVA, but to a lesser extent. These chain length effects were attributed to changes in polymer confirmation when adsorbed on the crystal surface. Additionally, decreasing the percentage of hydroxyl groups on the PVA polymer backbone reduced the ability of the polymer to inhibit the transformation and changing the degree of substitutions of methyl and hydroxypropyl groups on the cellulosic polymer backbone had no effect on the transformation.

  3. Biosorption of clofibric acid and carbamazepine in aqueous solution by agricultural waste rice straw.

    Science.gov (United States)

    Liu, Zhanguang; Zhou, Xuefei; Chen, Xiaohua; Dai, Chaomeng; Zhang, Juan; Zhang, Yalei

    2013-12-01

    Due to their widespread use, clofibric acid (CA) and carbamazepine (CBZ) have been frequently detected simultaneously at relatively high concentrations in aquatic environments. In this study, agricultural waste rice straw was employed as a potentially low-cost, effective and easy-to-operate biosorbent (RSB) to remove CA and CBZ. The adsorption of both pharmaceuticals followed pseudo second-order kinetics, and intraparticle diffusion was an important rate-limiting step. The adsorption isotherms of both drugs were fit well with Freundlich model. The adsorption of CA onto RSB was exothermic and was more likely to be dominated by physical processes, while the adsorption of CBZ was endothermic. Solution pH was determined to be the most important factor for CA adsorption, such that the adsorption capacity of CA onto RSB increased with the decline of solution pH. In the lower range of solution pH below 3.1, the CA removal efficiency was enhanced with the increase of biosorbent dosage. The CBZ removal efficiency was enhanced with the increase of RSB dosage without pH control. The maximum adsorption capacities were 126.3 mg/g for CA and 40.0 mg/g for CBZ.

  4. Carbamazepine and diclofenac: removal in wastewater treatment plants and occurrence in water bodies.

    Science.gov (United States)

    Zhang, Yongjun; Geissen, Sven-Uwe; Gal, Carmen

    2008-11-01

    In the aquatic environment, pharmaceuticals have been widely found. Among them, carbamazepine and diclofenac were detected at the highest frequency. To evaluate the worldwide environmental impacts of both drugs, their global consumption volumes are estimated, based on the dose per capita. The metabolites of these pharmaceuticals are also of environmental concerns, especially trans-10,11-dihydro-10,11- dihydroxycarbamazepine (CBZ-diol) which probably has a similar concentration in water bodies to that of its parent drug. The removal efficiencies and mechanisms of both drugs in the wastewater treatment plants (WWTPs) are discussed with the actual state of knowledge. The occurrences of both drugs are examined in various water bodies including WWTP effluents, surface waters, groundwater and drinking water. Their chemical, physical and pharmacological properties are also addressed in context, which can largely influence their environmental behaviors. The ecotoxicological studies of both drugs imply that they do not easily cause acute toxic effects at their environmental concentrations. However their chronic effects need cautious attention.

  5. Carbamazepine-Fumaric Acid Co-Crystal Screening Using Solution Based Method

    Directory of Open Access Journals (Sweden)

    Abd Rahim Syarifah

    2016-01-01

    Full Text Available Co-crystals is a multi-component system which connected by non-covalent interactions, present physically as a solid form under ambient conditions. Nowadays, co-crystal has becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ and fumaric acid (FUM co-crystal former (CCF using non-stoichiometric method (addition of CBZ to CCF saturated solution and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD, Differential Scanning Calorimetry (DSC and Fourier Transform Infrared (FT-IR. The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method where no crystal was found precipitate. The findings from this study revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvent systems.

  6. Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain

    Directory of Open Access Journals (Sweden)

    Shanshan Liu

    2018-01-01

    Full Text Available Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs. The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm with high drug loading (around 35% and high entrapment efficiency (around 80%. The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.

  7. Application of nanofiltration for the removal of carbamazepine, diclofenac and ibuprofen from drinking water sources.

    Science.gov (United States)

    Vergili, I

    2013-09-30

    Pharmaceutical active compounds (PhACs) are persistent during the process used to treat drinking water and, because drinking water treatment plants are not specifically designed to remove PhACs, these compounds are found in drinking water. Although there are currently no regulations or drinking water directives for PhACs, precautionary principles suggest ensuring maximal removal of PhACs through improved or existing treatment techniques. This study was designed to investigate the performance of a nanofiltration membrane in cross-flow filtration equipment for the removal of three PhACs [carbamazepine (CBZ), diclofenac (DIC) and ibuprofen (IBU)] that were spiked in water taken from a drinking water treatment plant using surface water. Because of their low solubilities, high log Kow values, low dipole moments and negative charges, higher rejection values were obtained for DIC and IBU. Low to moderate rejection values were most likely due to the small molecular sizes of the PhACs (i.e., MW water. Flux declines obtained from DIC studies was attributed to the adsorption of DIC ions inside the membrane pores, which decreases the flux. The most evident change in the FT-IR spectrum after nanofiltration was the appearance of new intense bands at 1072 cm(-1) and 1011 cm(-1), indicating the deposition of calcium salts on the membrane surface. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A microbial electro-fenton cell for removing carbamazepine in wastewater with electricity output.

    Science.gov (United States)

    Wang, Wei; Lu, Yaobin; Luo, Haiping; Liu, Guangli; Zhang, Renduo; Jin, Song

    2018-03-27

    High electrical energy is required for the electro-Fenton process to remove pharmaceuticals and personal care products (PPCPs) in wastewater. The aim of this study was to develop a novel and more cost-effective process, specifically a microbial electro-Fenton cell (MeFC), for treating PPCPs in wastewater. Acetylene black was selected as the catalyst for H 2 O 2 electrogeneration and Fe-Mn binary oxide for hydroxyl radical production. In addition to lowering energy needs, the MeFC produced a maximum power density of 112 ± 11 mW/m 2 with 1 g/L acetate as a representative substrate and 10 mg/L carbamazepine (CBZ) as a typical PPCP. Comparing with electro-Fenton process, the CBZ removal in the MeFC was 38% higher within 24 h operation (90% vs. 62%). Furthermore, the CBZ removal rate in the MeFC was 10-100 times faster than that in other biological treatment processes. Such enhanced degradation of CBZ in the MeFC was attributed to the synergistic reactions between radical oxidation of CBZ and biodegradation of degradative intermediates. The MeFC provides a promising method to remove PPCPs from wastewater coupling with efficient removal of other biodegradable organics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Interaction of Carbamazepine with Herbs, Dietary Supplements, and Food: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Sophia Yui Kau Fong

    2013-01-01

    Full Text Available Background. Carbamazepine (CBZ is a first-line antiepileptic drug which may be prone to drug interactions. Systematic review of herb- and food-drug interactions on CBZ is warranted to provide guidance for medical professionals when prescribing CBZ. Method. A systematic review was conducted on six English databases and four Chinese databases. Results. 196 out of 3179 articles fulfilled inclusion criteria, of which 74 articles were reviewed and 33 herbal products/dietary supplement/food interacting with CBZ were identified. No fatal or severe interactions were documented. The majority of the interactions were pharmacokinetic-based (80%. Traditional Chinese medicine accounted for most of the interactions (n=17, followed by food (n=10, dietary supplements (n=3, and other herbs/botanicals (n=3. Coadministration of 11 and 12 of the studied herbal products/dietary supplement/food significantly decreased or increased the plasma concentrations of CBZ. Regarding pharmacodynamic interaction, Xiao-yao-san, melatonin, and alcohol increased the side effects of CBZ while caffeine lowered the antiepileptic efficacy of CBZ. Conclusion. This review provides a comprehensive summary of the documented interactions between CBZ and herbal products/food/dietary supplements which assists healthcare professionals to identify potential herb-drug and food-drug interactions, thereby preventing potential adverse events and improving patients’ therapeutic outcomes when prescribing CBZ.

  10. [Drug rash with eosinophilia and systemic symptoms syndrome induced by carbamazepine: Case report].

    Science.gov (United States)

    Marín, Jorge Alonso; Ortega, Mayra Alexandra; Sánchez, Isaura Pilar; Pacheco, José Armando

    2017-06-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases.We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient's condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.

  11. Human Embryonic Stem Cell Therapy in Crohn’s Disease: A Case Report

    Science.gov (United States)

    Shroff, Geeta

    2016-01-01

    Patient: Male, 21 Final Diagnosis: Crohn’s disease Symptoms: Intolerance to specific foods • abdominal pain and diarrhea Medication: Human embryonic stem cell therapy Clinical Procedure: Human embryonic stem cell transplantation Specialty: Gastroenterology Objective: Unusual or unexpected effect of treatment Background: Crohn’s disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565 000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn’s disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn’s disease. Case Report: A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Conclusions: Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn’s disease. PMID:26923312

  12. The impacts of pharmaceutical drugs under ocean acidification: New data on single and combined long-term effects of carbamazepine on Scrobicularia plana.

    Science.gov (United States)

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Figueira, Etelvina; Soares, Amadeu M V M

    2016-01-15

    Ocean acidification and increasing discharges of pharmaceutical contaminants into aquatic systems are among key and/or emerging drivers of environmental change affecting marine ecosystems. A growing body of evidence demonstrates that ocean acidification can have direct and indirect impacts on marine organisms although combined effects with other stressors, namely with pharmaceuticals, have received very little attention to date. The present study aimed to evaluate the impacts of the pharmaceutical drug Carbamazepine and pH 7.1, acting alone and in combination, on the clam Scrobicularia plana. For this, a long-term exposure (28 days)was conducted and a set of oxidative stress markers was investigated. The results obtained showed that S. plana was able to develop mechanisms to prevent oxidative damage when under low pH for a long period, presenting higher survival when exposed to this stressor compared to CBZ or the combination of CBZ with pH 7.1. Furthermore, the toxicity of CBZ on S. plana was synergistically increased under ocean acidification conditions (CBZ + pH 7.1): specimens survival was reduced and oxidative stress was enhanced when compared to single exposures. These findings add to the growing body of evidence that ocean acidification will act to increase the toxicity of CBZ to marine organisms,which has clear implications for coastal benthic ecosystems suffering chronic pollution from pharmaceutical drugs.

  13. Guidelines for human embryonic stem cell research

    National Research Council Canada - National Science Library

    Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council

    2005-01-01

    Since 1998, the volume of research being conducted using human embryonic stem (hES) cells has expanded primarily using private funds because of restrictions on the use of federal funds for such research...

  14. Biomechanical forces promote embryonic haematopoiesis

    Science.gov (United States)

    Adamo, Luigi; Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Mack, Peter J.; Gracia-Sancho, Jorge; Suchy-Dicey, Astrid; Yoshimoto, Momoko; Lensch, M. William; Yoder, Mervin C.; García-Cardeña, Guillermo; Daley, George Q.

    2009-01-01

    Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system1,2. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3–5), a master regulator of haematopoiesis, and give rise to haematopoietic cells4. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential6. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41+c-Kit+ haematopoietic progenitor cells7,concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the paraaortic splanchnopleura/aorta–gonads–mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling8, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development. PMID:19440194

  15. Simple and accurate measurement of carbamazepine in surface water by use of porous membrane-protected micro-solid-phase extraction coupled with isotope dilution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Hui Ling [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); Wong, Lingkai [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Liu, Qinde, E-mail: liu_qinde@hsa.gov.sg [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Teo, Tang Lin; Lee, Tong Kooi [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Lee, Hian Kee, E-mail: chmleehk@nus.edu.sg [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore)

    2016-03-17

    To achieve fast and accurate analysis of carbamazepine in surface water, we developed a novel porous membrane-protected micro-solid-phase extraction (μ-SPE) method, followed by liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) analysis. The μ-SPE device (∼0.8 × 1 cm) was fabricated by heat-sealing edges of a polypropylene membrane sheet to devise a bag enclosing the sorbent. The analytes (both carbamazepine and isotope-labelled carbamazepine) were first extracted by μ-SPE device in the sample (10 mL) via agitation, then desorbed in an organic solvent (1 mL) via ultrasonication. Several parameters such as organic solvent for pre-conditioning of μ-SPE device, amount of sorbent, adsorption time, and desorption solvent and time were investigated to optimize the μ-SPE efficiency. The optimized method has limits of detection and quantitation estimated to be 0.5 ng L{sup −1} and 1.6 ng L{sup −1}, respectively. Surface water samples spiked with different amounts of carbamazepine (close to 20, 500, and 1600 ng L{sup −1}, respectively) were analysed for the validation of method precision and accuracy. Good precision was obtained as demonstrated by relative standard deviations of 0.7% for the samples with concentrations of 500 and 1600 ng kg{sup −1}, and 5.8% for the sample with concentration of 20 ng kg{sup −1}. Good accuracy was also demonstrated by the relative recoveries in the range of 96.7%–103.5% for all samples with uncertainties of 1.1%–5.4%. Owing to the same chemical properties of carbamazepine and isotope-labelled carbamazepine, the isotope ratio in the μ-SPE procedure was accurately controlled. The use of μ-SPE coupled with IDMS analysis significantly facilitated the fast and accurate measurement of carbamazepine in surface water. - Highlights: • μ-SPE coupled with IDMS for the measurement of carbamazepine. • The method is the first report of coupling μ-SPE with IDMS. • μ-SPE is fast, time

  16. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  17. Transformation products and reaction pathways of carbamazepine during photocatalytic and sonophotocatalytic treatment

    International Nuclear Information System (INIS)

    Jelic, A.; Michael, I.; Achilleos, A.; Hapeshi, E.; Lambropoulou, D.; Perez, S.; Petrovic, M.; Fatta-Kassinos, D.; Barcelo, D.

    2013-01-01

    Highlights: • Degradation of CBZ during US, TiO 2 /UV and TiO 2 /UV/US processes has been evaluated. • The combined TiO 2 /UV/US oxidation resulted in significant enhancement of the CBZ degradation rate. • Transformation products were identified and the transformation pathways were proposed. • An acute toxicity test showed an increase in toxicity over the time-course of the studied processes. -- Abstract: This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO 2 -based heterogeneous photocatalysis under UV-A and simulated solar irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e. sonophotocatalysis) in demineralized water, ground water and effluent wastewater. The processes were compared with respect to substrate conversion rate and the extent of DOC reduction as a measure of mineralization. CBZ was degraded following a pseudo-first order kinetics. Sonophotocatalysis provided the highest rate of CBZ transformation over the time-course of the experiment while the degree of DOC removal in pure water was similar for all the studied treatments (around 40%), and always lower than CBZ conversion. This indicated that a considerable organic load remained in the treated solutions that could also be attributed to the presence of persistent oxidation products. UPLC–(+ESI)-QToF-MS was employed to determine major CBZ-related transformation products. Several recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A Daphnia magna bioassay was used to evaluate the potential toxicity of the samples collected at different time points showing that the mixtures were highly toxic to D. magna

  18. Degradation of carbamazepine using hydrodynamic cavitation combined with advanced oxidation processes.

    Science.gov (United States)

    Thanekar, Pooja; Panda, Mihir; Gogate, Parag R

    2018-01-01

    Degradation of carbamazepine (CBZ), a widely detected recalcitrant pharmaceutical in sewage treatment plant (STP) effluent, has been studied in the present work using combination of hydrodynamic cavitation (HC) and advanced oxidation processes (AOPs). Due to its recalcitrant nature, it cannot be removed effectively by the conventional wastewater treatment plants (WWTPs) which make CBZ a pharmaceutical of very high environmental relevance and impact as well as stressing the need for developing new treatment schemes. In the present study, the effect of inlet pressure (3-5bar) and operating pH (3-11) on the extent of degradation have been initially studied with an objective of maximizing the degradation using HC alone. The established optimum conditions as pressure of 4bar and pH of 4 resulted in maximum degradation of CBZ as 38.7%. The combined approaches of HC with ultraviolet irradiation (HC+UV), hydrogen peroxide (HC+H 2 O 2 ), ozone (HC+O 3 ) as well as combination of HC, H 2 O 2 and O 3 (HC+H 2 O 2 +O 3 ) have been investigated under optimized pressure and operating pH. It was observed that a significant increase in the extent of degradation is obtained for the combined operations of HC+H 2 O 2 +O 3 , HC+O 3 , HC+H 2 O 2 , and HC+UV with the actual extent of degradation being 100%, 91.4%, 58.3% and 52.9% respectively. Kinetic analysis revealed that degradation of CBZ fitted into first order kinetics model for all the approaches. The processes were also compared on the basis of cavitational yield and also in terms of total treatment cost. Overall, it has been demonstrated that combined process of HC, H 2 O 2 and O 3 can be effectively used for treatment of wastewater containing CBZ. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Preventive Effect of Vitamin B6 on Developmental Toxicity of Carbamazepine in Mice

    Directory of Open Access Journals (Sweden)

    Mohammad Afshar

    2011-03-01

    Full Text Available Objective(sCarbamazepine (CBZ is an antiepileptic drug that is used widely for the treatment of epileptic seizures. Neural tube defects (NTDs, growth retardation, and nail hypoplasia are the most common features of teratogenic effects of this drug. The purpose of this study was to examine the effect of vitamin B6 on the developmental toxicity of CBZ on mice.Materials and MethodsSixty BALB/c pregnant mice were divided into four experimental and two control groups. Two experimental groups received daily intraperitoneal injection (IP of 30 mg/kg (I or 60 mg/kg (II of CBZ on gestational days (GD 6 to 15. Two other experimental groups received daily IP injection of 30 mg/kg (III or 60 mg/kg (IV of CBZ with 10 mg/kg/day vitamin B6 by gavage 10 days prior to gestation and on GD 6 to 15. Two control groups received normal saline or Tween 20. Dams underwent Cesarean section on GD 18 and embryos were harvested. External/macroscopic observation of fetuses was done by stereomicroscope and external examination for malformations was recorded. Data analyzed by ANOVA and X2 test using SPSS software.ResultsThe mean weight and crown-rump of the fetuses in both CBZ-treated experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, eye malformations, NTDs, vertebral deformity, brachydactyly and growth retardation. Vitamin B6 treatment significantly reduced various CBZ-induced malformations.ConclusionThis study showed that vitamin B6 has a preventive effect on the developmental toxicity of CBZ in mice that can be pursued further for clinical research.

  20. Carbamazepine but not valproate induces CYP2A6 activity in smokers with mental illness

    Science.gov (United States)

    Williams, Jill M; Gandhi, Kunal K; Benowitz, Neal L

    2010-01-01

    BACKGROUND Anti-epileptic drugs (AED) are increasingly used in the management of serious mental illness yet their effects on nicotine metabolism have not been studied. METHODS This study investigated the effects of 3 AED (carbamazepine, CBZ; oxcarbazepine, OCB or valproic acid, VPA) on nicotine and nicotine metabolite levels in 149 smokers with schizophrenia and bipolar disorder who participated in an afternoon blood draw for nicotine, cotinine, and 3’-hydroxycotinine (3HC). The ratio of 3HC to cotinine was calculated as a marker of CYP2A6 metabolic activity. Eight smokers were taking CBZ, six were taking OCB and 40 were taking VPA. RESULTS The 3HC/cotinine ratio was significantly higher in individuals taking CBZ or OCB (combined, n=14) vs. those not taking it (mean 0.993 vs. 0.503; p< 0.001). The cotinine/cigarette per day ratio was significantly lower in individuals taking CBZ or OCB. The 3HC/cotinine ratios were also significantly higher in the subgroup of individuals taking CBZ (n=8) vs. those not taking it. There were no significant differences in nicotine or cotinine levels or 3HC/cotinine ratios in individuals taking VPA vs. those not taking it. We conducted backward stepwise linear regression models to identify predictors of the log transformed 3HC/cotinine ratios. Taking CBZ and number of cigarettes smoked per day were significant determinants of log 3HC/Cotinine. CONCLUSIONS CBZ likely induces hepatic metabolism via CYP2A6 and is associated with increased 3HC/Cotinine ratios. IMPACT Increased nicotine metabolism in individuals using AED has implications for increased smoking behavior and exposure to more tobacco toxins that warrants further study. PMID:20719908

  1. Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia.

    Science.gov (United States)

    Xue, Hui; Xiang, Wenping; Yu, Yichuan; Liu, Guorong; Chong, Yi; Zhou, Jiying

    2018-01-01

    Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ) plus betahistine mesilate tablets (BMT) (CBZ+BMT) and oxcarbazepine (OXC) plus BMT (OXC+BMT) in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT. VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed. In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group ( p =0.04). Subgroup analysis found that patients receiving BMT (18 mg) had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg). These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ hypersensitivity, and the synergistic effect could be increased along with the increased dose of BMT.

  2. Fate and transport of carbamazepine in soil aquifer treatment (SAT) infiltration basin soils.

    Science.gov (United States)

    Arye, Gilboa; Dror, Ishai; Berkowitz, Brian

    2011-01-01

    The transport and fate of the pharmaceutical carbamazepine (CBZ) were investigated in the Dan Region Reclamation Project (SHAFDAN), Tel-Aviv, Israel. Soil samples were taken from seven subsections of soil profiles (150 cm) in infiltration basins of a soil aquifer treatment (SAT) system. The transport characteristics were studied from the release dynamics of soil-resident CBZ and, subsequently, from applying a pulse input of wastewater containing CBZ. In addition, a monitoring study was performed to evaluate the fate of CBZ after the SAT. Results of this study indicate adsorption, and consequently retardation, in CBZ transport through the top soil layer (0-5 cm) and to a lesser extent in the second layer (5-25 cm), but not in deeper soil layers (25-150 cm). The soluble and adsorbed fractions of CBZ obtained from the two upper soil layers comprised 45% of the total CBZ content in the entire soil profile. This behavior correlated to the higher organic matter content observed in the upper soil layers (0-25 cm). It is therefore deduced that when accounting for the full flow path of CBZ through the vadose zone to the groundwater region, the overall transport of CBZ in the SAT system is essentially conservative. The monitoring study revealed that the average concentration of CBZ decreased from 1094 ± 166 ng L⁻¹ in the recharged wastewater to 560 ± 175 ng L⁻¹ after the SAT. This reduction is explained by dilution of the recharged wastewater with resident groundwater, which may occur as it flows to active reclamation wells. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. UV/chlorine treatment of carbamazepine: Transformation products and their formation kinetics.

    Science.gov (United States)

    Pan, Yanheng; Cheng, ShuangShuang; Yang, Xin; Ren, Jingyue; Fang, Jingyun; Shang, Chii; Song, Weihua; Lian, Lushi; Zhang, Xinran

    2017-06-01

    Carbamazepine (CBZ) is one of the pharmaceuticals most frequently detected in the aqueous environment. This study investigated the transformation products when CBZ is degraded by chlorine under ultraviolet (UV) irradiation (the UV/chlorine process). Detailed pathways for the degradation of CBZ were elucidated using ultra-high performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry (QTOF-MS). CBZ is readily degraded by hydroxyl radicals (HO) and chlorine radicals (Cl) in the UV/chlorine process, and 24 transformation products were identified. The products indicate that the 10,11-double bond and aromatic ring in CBZ are the sites most susceptible to attack by HO and Cl. Subsequent reaction produces hydroxylated and chlorinated aromatic ring products. Four specific products were quantified and their evolution was related with the chlorine dose, pH, and natural organic matter concentration. Their yields showed an increase followed by a decreasing trend with prolonged reaction time. CBZ-10,11-epoxide (I), the main quantified transformation product from HO oxidation, was observed with a peak transformation yield of 3-32% depending on the conditions. The more toxic acridine (IV) was formed involving both HO and Cl with peak transformation yields of 0.4-1%. All four quantified products together amounted to a peak transformation yield of 34.5%. The potential toxicity of the transformation products was assayed by evaluating their inhibition of the bioluminescence of the bacterium Vibrio Fischeri. The inhibition increased at first and the decreased at longer reaction times, which was in parallel with the evolution of transformation products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Carbamazepine (Tegretol) inhibits in vivo iodide uptake and hormone synthesis in rat thyroid glands

    International Nuclear Information System (INIS)

    Villa, S.M.; Alexander, N.M.

    1987-01-01

    Decreased serum concentrations of T3 and T4 occur in patients treated with the anticonvulsant drug carbamazepine (CBZ), but with rare exception, these patients remain euthyroid. The mechanism that accounts for diminished hormone levels is unknown, and our objective was to study the direct effect of CBZ on iodide uptake and hormone synthesis in thyroid glands of CBZ-treated and pair-fed control rats. Chronic ingestion (per os) of CBZ in male rats reduced the four hour thyroid 131I-iodide uptake by approximately 60%. This inhibition occurred after the animals had received sufficient CBZ to attain plasma CBZ concentrations of 0.8 microgram/ml. Continued treatment with CBZ ranging from 560 to 800 mg/kg/day for 14 days did not result in further inhibition of iodide uptake even though the plasma CBZ concentrations had increased 6-20 fold. No inhibition of iodide uptake was apparent when the animals initially received CBZ ranging from 40 to 152 mg/kg body weight for 22 days when there were no detectable levels of plasma CBZ. Overall growth rates of CBZ-treated rats were slightly (6-10%) less than the pair-fed control animals. Plasma T4 concentrations were reduced by 18% (p less than 0.05) in the CBZ-fed animals, while T3 concentrations were diminished by 53% (p less than 0.01). CBZ appeared to alter thyroidal iodide transport because the thyroid:plasma iodide ratios were decreased by 26% in the drug-treated rats. The distribution of radioiodine in thyroidal iodoamino acids was essentially the same in both groups of rats but the absolute quantities of radioiodine were more than 2.5 times greater in the control rats. CBZ failed to inhibit peroxidase-catalyzed iodide and guaiacol oxidation in vitro

  5. Metabolic syndrome and anticonvulsants: A comparative study of valproic acid and carbamazepine.

    Science.gov (United States)

    Rakitin, Aleksei; Kõks, Sulev; Haldre, Sulev

    2016-05-01

    The aim of this study was to compare the risk of metabolic syndrome (MS) and evaluate related factors for MS among people with epilepsy treated with valproate (VPA) or carbamazepine (CBZ). A total of 213 adult patients with epilepsy treated with VPA (n=118) or CBZ (n=95) monotherapy were included in the study. Participants were evaluated for the presence of MS, diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. In the multiple logistic regression analysis, the risk of MS in CBZ- and VPA-treated patients was similar (odds ratio [OR]=0.99; 95% confidence interval [CI], 0.43-2.26; P=0.979). A lower proportion of CBZ-treated patients had abnormally low levels of high-density lipoprotein cholesterol (OR=0.10; 95% CI, 0.02-0.42; P=0.002), whereas a lower proportion of VPA-treated patients had abnormally high concentrations of fasting blood glucose (OR=0.30; 95% CI, 0.13-0.69; P=0.004). Females treated with VPA tended to have a higher risk of MS (OR=1.48; 95% CI, 0.50-4.41; P=0.485) compared to males (OR=0.74; 95% CI, 0.28-1.96; P=0.551), although this difference was not statistically significant. Although the overall risk of MS was similar in patients with epilepsy who were treated with VPA or CBZ, the distribution of MS components differed between treatment groups. Patients treated with CBZ or VPA less frequently had decreased high-density lipoprotein cholesterol levels or increased blood glucose concentrations, respectively. Females on VPA treatment could be at higher risk of MS than males. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Transformation products and reaction pathways of carbamazepine during photocatalytic and sonophotocatalytic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jelic, A. [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Michael, I.; Achilleos, A.; Hapeshi, E. [Department of Civil and Environmental Engineering, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Nireas, International Water Research Centre, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Lambropoulou, D. [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Perez, S., E-mail: spsqam@idaea.csic.es [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Petrovic, M. [Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona (Spain); Fatta-Kassinos, D. [Department of Civil and Environmental Engineering, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Nireas, International Water Research Centre, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Barcelo, D. [Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona (Spain)

    2013-12-15

    Highlights: • Degradation of CBZ during US, TiO{sub 2}/UV and TiO{sub 2}/UV/US processes has been evaluated. • The combined TiO{sub 2}/UV/US oxidation resulted in significant enhancement of the CBZ degradation rate. • Transformation products were identified and the transformation pathways were proposed. • An acute toxicity test showed an increase in toxicity over the time-course of the studied processes. -- Abstract: This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO{sub 2}-based heterogeneous photocatalysis under UV-A and simulated solar irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e. sonophotocatalysis) in demineralized water, ground water and effluent wastewater. The processes were compared with respect to substrate conversion rate and the extent of DOC reduction as a measure of mineralization. CBZ was degraded following a pseudo-first order kinetics. Sonophotocatalysis provided the highest rate of CBZ transformation over the time-course of the experiment while the degree of DOC removal in pure water was similar for all the studied treatments (around 40%), and always lower than CBZ conversion. This indicated that a considerable organic load remained in the treated solutions that could also be attributed to the presence of persistent oxidation products. UPLC–(+ESI)-QToF-MS was employed to determine major CBZ-related transformation products. Several recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A Daphnia magna bioassay was used to evaluate the potential toxicity of the samples collected at different time points showing that the mixtures were highly toxic to D. magna.

  7. Enantioselective assay for therapeutic drug monitoring of eslicarbazepine acetate: no interference with carbamazepine and its metabolites.

    Science.gov (United States)

    Alves, Gilberto; Fortuna, Ana; Sousa, Joana; Direito, Rosa; Almeida, Anabela; Rocha, Marília; Falcão, Amílcar; Soares-da-Silva, Patrício

    2010-08-01

    As add-on therapy, phase III clinical trials of eslicarbazepine acetate (ESL) conducted in patients with refractory partial-onset seizures have shown good efficacy, safety, and tolerability, even in patients taking carbamazepine (CBZ) at baseline (approximately 60% of the enrolled patients). Thus, considering the pharmacological disadvantages of CBZ and the similar efficacy spectrum of CBZ and ESL, switching to ESL may be successful in many patients. As ESL is a prodrug almost instantaneously converted to S-licarbazepine (S-Lic; approximately 95%), an interest in therapeutic drug monitoring (TDM) of S-Lic is likely to develop in the future. This study investigated the plasma concentrations of S-Lic and R-licarbazepine (R-Lic) enantiomers in patients under CBZ long-term treatment to assess the potential interference of CBZ or its metabolites in the enantioselective TDM of ESL (using S-Lic concentrations). A chiral high-performance liquid chromatography assay with ultraviolet detection (HPLC-UV) previously developed and validated by our research group was used. Twenty-four patients admitted to the Coimbra University Hospital and supposedly receiving CBZ long-term treatment were identified. Blood samples were collected from patients and serum CBZ concentrations were measured by the usual TDM protocol. Aliquots of plasma from such patients were also submitted to a chiral HPLC-UV analysis. The bioanalytical data indicated that S-Lic and R-Lic were not present at detectable concentrations in plasma samples of the CBZ-treated patients. The chromatograms generated by the analysis of patient plasma samples, when compared with those obtained from blank plasma samples spiked with S-Lic and R-Lic, clearly showed the absence of interferences at the retention times of both Lic enantiomers. These data support the usefulness of the chiral HPLC-UV method used for the enantioselective TDM of ESL (using S-Lic) for programs in which switching from CBZ to ESL is implemented.

  8. Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes (Danio rerio).

    Science.gov (United States)

    Fraz, Shamaila; Lee, Abigail H; Wilson, Joanna Y

    2018-05-01

    Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17.5 ± 1.78 and 11.2 ± 1.08 μg/L respectively. A 67 day exposure led to reduced reproductive output and lowered whole body, plasma, and testicular 11-ketotestosterone (11-KT). Testicular production of 11-KT was examined post exposure (42 days) using ex vivo cultures to determine basal and stimulated steroid production. The goal was to ascertain the step impaired in the steroidogenic pathway by each compound. Ex vivo 11-KT production in testes from males chronically exposed to GEM and CBZ was lower than that from unexposed males. Although hCG, 25-OH cholesterol, and pregnenolone stimulation increased 11-KT production in all treatment groups over basal levels, hCG stimulated 11-KT production remained significantly less in testes from exposed males compared to controls. 25-OH cholesterol and pregnenolone stimulated 11-KT production was similar between GEM and control groups but the CBZ group had lower 11-KT production than controls with both stimulants. We therefore propose that chronic GEM and CBZ exposure can reduce production of 11-KT in testes through direct effects independent of mediation through HPG axis. The biochemical processes for steroid production appear un-impacted by GEM exposure; while CBZ exposure may influence steroidogenic enzyme expression or function. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

    Science.gov (United States)

    Powell, Graham; Holmes, Emily A F; Plumpton, Catrin O; Ring, Adele; Baker, Gus A; Jacoby, Ann; Pirmohamed, Munir; Marson, Anthony G; Hughes, Dyfrig A

    2015-11-01

    Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV. The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice. © 2015 The British Pharmacological Society.

  10. Immunostaining of dissected zebrafish embryonic heart.

    Science.gov (United States)

    Yang, Jingchun; Xu, Xiaolei

    2012-01-10

    Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments

  11. An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine.

    Science.gov (United States)

    Plósz, Benedek Gy; Langford, Katherine H; Thomas, Kevin V

    2012-11-01

    Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM-X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full-scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re-transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between

  12. Reproductive performance and embriotoxicity of rats exposed to carbamazepine Performance reprodutiva e embriotoxicidade de ratos expostos à carbamazepina

    Directory of Open Access Journals (Sweden)

    Marli Gerenutti

    2008-09-01

    Full Text Available To study the possible effects of carbamazepine in rats during pregnancy and fetuses' physical development, carbamazepine solubilized in propilenglycol was orally administered (20 and 40 mg/kg to the female rats from the 2nd to the 19th days of pregnancy. Propilenglycol was administered to the control group. The animals were sacrificed on the 20th day, when 50% of the offspring were fixed in Bouin's solution and the remaining 50% were submitted to diaphanization. The carbamazepine administration caused reduction on weight gain of pregnant rats and did not damage the females' reproductive performance. In the fetuses' physical development, it was observed a flattening on the skull soft tissues and bones; delay in the skull bone development; cartilage calcification increase between hip and femur and reduction in the number of the sternum ossifications. Although carbamazepine has not caused general changes over female rats' reproductive performance, it produced significant alterations in the development of the fetuses' skeletal parameters.Este trabalho teve como objetivo estudar os possíveis efeitos da administração da carbamazepina na gestação de ratas. A solução glicólica de carbamazepina foi administrada por via oral (20 mg/kg e 40 mg/kg, às ratas do 2º ao 19º dia de gestação. O grupo controle recebeu solução de propilenoglicol. Após a realização da cesária, no 20º dia, 50% dos filhotes foram fixados em Bouin e os outros 50% passaram por processo de diafanização. Estes estudos mostraram que embora a administração de carbamazepina tenha promovido redução do ganho de peso de ratas prenhes, não prejudicou a performance reprodutiva de fêmeas. Nos fetos, observou-se achatamento de tecidos moles e ossos do crânio, retardo no desenvolvimento ósseo do crânio, aumento da calcificação da cartilagem entre o quadril e o fêmur e redução no número de ossificações do esterno. Estes dados, tomados em conjunto, indicam que a

  13. Removal of ibuprofen, naproxen and carbamazepine in aqueous solution onto natural clay: equilibrium, kinetics, and thermodynamic study

    Science.gov (United States)

    Khazri, Hassen; Ghorbel-Abid, Ibtissem; Kalfat, Rafik; Trabelsi-Ayadi, Malika

    2017-10-01

    This study aimed to describe the adsorption of three pharmaceuticals compounds (ibuprofen, naproxen and carbamazepine) onto natural clay on the basis of equilibrium parameters such as a function of time, effect of pH, varying of the concentration and the temperature. Adsorption kinetic data were modeled using the Lagergren's first-order and the pseudo-second-order kinetic equations. The kinetic results of adsorption are described better using the pseudo-second order model. The isotherm results were tested in the Langmuir, Freundlich and Dubinin-Radushkevich models. The thermodynamic parameters obtained indicate that the adsorption of pharmaceuticals on the clay is a spontaneous and endothermic process.

  14. Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories : The Rotterdam Predict Study

    NARCIS (Netherlands)

    Koning, Irene V; Groenenberg, Irene A L; Gotink, Anniek W; Willemsen, Sten P; Gijtenbeek, Manon; Dudink, Jeroen; Go, Attie T J I; Reiss, Irwin K M; Steegers, Eric A P; Steegers-Theunissen, Régine P M

    2015-01-01

    We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks

  15. Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Hadjira Rabti

    2014-06-01

    Full Text Available Elementary osmotic pump (EOP is a unique extended release (ER drug delivery system based on the principle of osmosis. It has the ability to minimize the amount of the drug, accumulation and fluctuation in drug level during chronic uses. Carbamazepine (CBZ, a poorly water-soluble antiepileptic drug, has serious side effects on overdoses and chronic uses. The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance. Firstly, a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug. Then, designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance (ANOVA, respectively. The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone (PVP K30 and sodium lauryl sulfate (SLS. The plasticizer amount and molecular weight (MW together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane (SPM thickness inversely influence the release rate. In addition, the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core. Further, orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm. In this study we report the successful formulation of CBZ-EOP tablets, which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80% of CBZ at a rate of approximately zero order for up to 12 h.

  16. Chromatin in embryonic stem cell neuronal differentiation.

    Science.gov (United States)

    Meshorer, E

    2007-03-01

    Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

  17. Gene expression response to EWS–FLI1 in mouse embryonic cartilage

    Directory of Open Access Journals (Sweden)

    Miwa Tanaka

    2014-12-01

    Full Text Available Ewing's sarcoma is a rare bone tumor that affects children and adolescents. We have recently succeeded to induce Ewing's sarcoma-like small round cell tumor in mice by expression of EWS–ETS fusion genes in murine embryonic osteochondrogenic progenitors. The Ewing's sarcoma precursors are enriched in embryonic superficial zone (eSZ cells of long bone. To get insights into the mechanisms of Ewing's sarcoma development, gene expression profiles between EWS–FLI1-sensitive eSZ cells and EWS–FLI1-resistant embryonic growth plate (eGP cells were compared using DNA microarrays. Gene expression of eSZ and eGP cells (total, 30 samples was evaluated with or without EWS–FLI1 expression 0, 8 or 48 h after gene transduction. Our data provide useful information for gene expression responses to fusion oncogenes in human sarcoma.

  18. Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Manolis Gialitakis

    2017-11-01

    Full Text Available The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we have investigated the AHR interactome in embryonic stem cells by mass spectrometry and show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylation. The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling.

  19. The role of the pupal determinant broad during embryonic development of a direct-developing insect

    Science.gov (United States)

    Rynerson, Melody R.; Truman, James W.; Riddiford, Lynn M.

    2010-01-01

    Metamorphosis is one of the most common, yet dramatic of life history strategies. In insects, complete metamorphosis with morphologically distinct larval stages arose from hemimetabolous ancestors that were more direct developing. Over the past century, several ideas have emerged that suggest the holometabolous pupa is developmentally homologous to the embryonic stages of the hemimetabolous ancestor. Other theories consider the pupal stage to be a modification of a hemimetabolous nymph. To address this question, we have isolated an ortholog of the pupal determinant, broad (br), from the hemimetabolous milkweed bug and examined its role during embryonic development. We show that Oncopeltus fasciatus br (Of'br) is expressed in two phases. The first occurs during germ band invagination and segmentation when Of'br is expressed ubiquitously in the embryonic tissues. The second phase of Of'br expression appears during the pronymphal phase of embryogenesis and persists through nymphal differentiation to decline just before hatching. Knock-down of Of'br transcripts results in defects that range from posterior truncations in the least-affected phenotypes to completely fragmented embryonic tissues in the most severe cases. Analysis of the patterning genes engrailed and hunchback reveal loss of segments and a failure in neural differentiation after Of'br depletion. Finally, we show that br is constitutively expressed during embyrogenesis of the ametabolous firebrat, Thermobia domestica. This suggests that br expression is prominent during embryonic development of ametabolous and hemimetabolous insects but was lost with the emergence of the completely metamorphosing insects. PMID:20127251

  20. Arrested embryonic development: a review of strategies to delay hatching in egg-laying reptiles

    Science.gov (United States)

    Rafferty, Anthony R.; Reina, Richard D.

    2012-01-01

    Arrested embryonic development involves the downregulation or cessation of active cell division and metabolic activity, and the capability of an animal to arrest embryonic development results in temporal plasticity of the duration of embryonic period. Arrested embryonic development is an important reproductive strategy for egg-laying animals that provide no parental care after oviposition. In this review, we discuss each type of embryonic developmental arrest used by oviparous reptiles. Environmental pressures that might have directed the evolution of arrest are addressed and we present previously undiscussed environmentally dependent physiological processes that may occur in the egg to bring about arrest. Areas for future research are proposed to clarify how ecology affects the phenotype of developing embryos. We hypothesize that oviparous reptilian mothers are capable of providing their embryos with a level of phenotypic adaptation to local environmental conditions by incorporating maternal factors into the internal environment of the egg that result in different levels of developmental sensitivity to environmental conditions after they are laid. PMID:22438503

  1. Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes

    Directory of Open Access Journals (Sweden)

    Chen Chia-Hui

    2012-05-01

    Full Text Available Abstract Background Carbamazepine (CBZ has been used in the treatment of bipolar disorder, both in acute mania and maintenance therapy, since the early 1970s. Here, we report a follow-up study of CBZ-treated bipolar patients in the Taipei City Psychiatric Centre. Methods Bipolar patients diagnosed according to the DSM-IV system and treated with CBZ at the Taipei City Psychiatric Centre had their charts reviewed to evaluate the efficacy and side effects of this medication during an average follow-up period of 10 years. Results A total of 129 bipolar patients (45 males, mean age: 45.7 ± 10.9 year were included in the analysis of CBZ efficacy used alone (n = 63 or as an add-on after lithium (n = 50 or valproic acid (n = 11, or the both of them (n = 5. The mean age of disease onset was 24.6 ± 9.5 years. The mean duration of CBZ use was 10.4 ± 5.2 year. The mean dose used was 571.3 ± 212.6 mg/day with a mean plasma level of 7.8 ± 5.9 μg/mL. Mean body weight increased from 62.0 ± 13.4 kg to 66.7 ± 13.1 kg during treatment. The frequencies of admission per year before and after CBZ treatment were 0.33 ± 0.46 and 0.14 ± 0.30, respectively. The most common side effects targeted the central nervous system (24%, including dizziness, ataxia and cognitive impairment. Other common side effects were gastrointestinal disturbances (3.6%, tremor (3.6%, skin rash (2.9%, and blurred vision (2.9%. Eighty-eight patients (68.2% were taking antipsychotics concomitantly. Ninety-six patients (74.4% needed to use benzodiazepines concomitantly. Sixty-three (48.8% patients had zero episodes in a 10-year follow-up period, compared to all patients having episodes prior to treatment. Using variable analysis, we found better response to CBZ in males than in females. Conclusions CBZ is efficacious in the maintenance treatment of bipolar disorder in naturalistic clinical practice, either as monotherapy

  2. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

    Directory of Open Access Journals (Sweden)

    Ghaydaa A Shehata

    2009-10-01

    Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

  3. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Michael R Due

    Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

  4. Production method of carbamazepine/saccharin cocrystal particles by using two solution mixing based on the ternary phase diagram

    Science.gov (United States)

    Kudo, Shoji; Takiyama, Hiroshi

    2014-04-01

    In the pharmaceutical field, improvement of drug solubility is required, and an interest in cocrystals is growing. Crystallization methods for industrial production of cocrystals have not been developed enough whereas many cocrystals have been prepared in order to find a new crystal form by screening in the laboratory. The objective of this study was the development of the crystallization method which is useful for the industrial production of cocrystal particles based on the phase diagram. A cocrystal of carbamazepine and saccharin was selected as a model substance. The ternary phase diagram of carbamazepine and saccharin in methanol at 303 K was measured. A cocrystallization method of mixing two kinds of different eutectic solutions was designed based on the ternary phase diagram. In order to adjust the cocrystallization conditions, the determination method of the driving force for cocrystal deposition such as supersaturation based on mass balance was proposed. The cocrystal particles were obtained under all the conditions of the five mixing ratios. From these experimental results, the relationship between the supersaturation and the induction time for nucleation was confirmed as well as conventional crystallization. In conclusion, the crystallization method for industrial production of cocrystal particles including the determination of the supersaturation was suggested.

  5. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Majeed Ullah

    2015-01-01

    Full Text Available The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25 in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS. At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

  6. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Science.gov (United States)

    Ullah, Majeed; Ullah, Hanif; Mahmood, Qaisar; Hussain, Izhar

    2015-01-01

    The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted. PMID:26380301

  7. Photocatalytic degradation of clofibric acid, carbamazepine and iomeprol using conglomerated TiO2 and activated carbon in aqueous suspension.

    Science.gov (United States)

    Ziegmann, Markus; Frimmel, Fritz H

    2010-01-01

    The combination of powdered activated carbon (PAC) and TiO(2) has been tested for synergistic/antagonistic effects in the photocatalytic degradation of carbamazepine, clofibric acid and iomeprol. Synergistic effects are thought to be caused by rapid adsorption on the PAC surface followed by diffusion to the TiO(2) surface and photocatalytic degradation. The Freundlich constant K(F) was used for comparing the sorption properties of the three substances and it was found that K(F) for clofibric acid was 3 times lower than for carbamazepine and iomeprol, regardless of the kind of PAC used. A PAC with a distinct tendency to form conglomerates was selected so that a high percentage of the PAC surface was in direct proximity to the TiO(2) surface. The photocatalytic degradation of the pharmaceutically active compounds studied followed pseudo-first order kinetics. Synergistic effects only occurred for clofibric acid (factor 1.5) and an inverse relationship between adsorption affinity and synergistic effects was found. High affinity of the target substances to the PAC surface seemed to be counterproductive for the photocatalytic degradation.

  8. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

    Science.gov (United States)

    Beig, Avital; Lindley, David; Miller, Jonathan M.; Agbaria, Riad; Dahan, Arik

    2016-01-01

    Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure. PMID:27826241

  9. Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

    Directory of Open Access Journals (Sweden)

    Avital Beig

    2016-10-01

    Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

  10. In vitro differentiation of mouse embryonic stem cells into functional ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... hepatocyte transplantation therapy and toxicity screening in drug discovery. Key words: Embryonic stem cells, hepatic-like cells, in vitro differentiation, sodium butyrate, ... from embryonic stem (ES) cell or induced pluripotent.

  11. the production of mouse embryonic stem cells

    Indian Academy of Sciences (India)

    MADU

    What history tells us VII. Twenty-five years ago: the production of mouse embryonic stem cells ... cells into the cavity of the blastocyst, it will be possible to test the effect of .... to the use of efficient immunosuppressive drugs like cyclosporin – was ...

  12. Testicular Embryonic Rhabdomyosarcoma, Case report with brief ...

    African Journals Online (AJOL)

    Testicular Embryonic Rhabdomyosarcoma, Case report with brief literature review. AM Adam, MMAM Ibnouf, IAF Allah. Abstract. Background: Rhabdomyosarcoma (RMS) is a malignant solid tumour arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites.

  13. How the embryonic chick brain twists.

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A

    2016-11-01

    During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain. © 2016 The Author(s).

  14. Embryonal rhabdomyosarcoma of the cervix | Ocheke | African ...

    African Journals Online (AJOL)

    Embryonal rhabdomyosarcoma (sarcoma botyroides) of the cervix, which is rare, is described in a 16-yearold. The combined use of chemotherapy, radiotherapy and surgery has markedly improved survival in those with this condition. However, our patient did not benefit from this treatment modality due to late presentation ...

  15. Embryonic Stem Cells and their Genetic Modification

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 2. Embryonic Stem Cells and their Genetic Modification - The Nobel Prize in Physiology or Medicine 2007. Mitradas M Panicker. General Article Volume 13 Issue 2 February 2008 pp 172-180 ...

  16. Transcriptome Landscapes of Mammalian Embryonic Cells

    NARCIS (Netherlands)

    Brinkhof, B.

    2015-01-01

    This thesis describes research on gene expression profiles from different embryonic stages and cell types to identify genes involved in pluripotency or differentiation in bovine and porcine cells. The results are compared with data from other mammals. RNA expression profiles of morula and blastocyst

  17. Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

    Directory of Open Access Journals (Sweden)

    Jonathan Göke

    2011-12-01

    Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

  18. Self-organization of human embryonic stem cells on micropatterns

    Science.gov (United States)

    Deglincerti, Alessia; Etoc, Fred; Guerra, M. Cecilia; Martyn, Iain; Metzger, Jakob; Ruzo, Albert; Simunovic, Mijo; Yoney, Anna; Brivanlou, Ali H.; Siggia, Eric; Warmflash, Aryeh

    2018-01-01

    Fate allocation in the gastrulating embryo is spatially organized as cells differentiate to specialized cell types depending on their positions with respect to the body axes. There is a need for in vitro protocols that allow the study of spatial organization associated with this developmental transition. While embryoid bodies and organoids can exhibit some spatial organization of differentiated cells, these methods do not yield consistent and fully reproducible results. Here, we describe a micropatterning approach where human embryonic stem cells are confined to disk-shaped, sub-millimeter colonies. After 42 hours of BMP4 stimulation, cells form self-organized differentiation patterns in concentric radial domains, which express specific markers associated with the embryonic germ layers, reminiscent of gastrulating embryos. Our protocol takes 3 days; it uses commercial microfabricated slides (CYTOO), human laminin-521 (LN-521) as extra-cellular matrix coating, and either conditioned or chemically-defined medium (mTeSR). Differentiation patterns within individual colonies can be determined by immunofluorescence and analyzed with cellular resolution. Both the size of the micropattern and the type of medium affect the patterning outcome. The protocol is appropriate for personnel with basic stem cell culture training. This protocol describes a robust platform for quantitative analysis of the mechanisms associated with pattern formation at the onset of gastrulation. PMID:27735934

  19. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    International Nuclear Information System (INIS)

    Theunissen, P.T.; Robinson, J.F.; Pennings, J.L.A.; Herwijnen, M.H. van; Kleinjans, J.C.S.; Piersma, A.H.

    2012-01-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  20. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    Energy Technology Data Exchange (ETDEWEB)

    Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  1. Development, validation and clinical application of an online-SPE-LC-HRMS/MS for simultaneous quantification of phenobarbital, phenytoin, carbamazepine, and its active metabolite carbamazepine 10,11-epoxide.

    Science.gov (United States)

    Qu, Lihua; Fan, Yuanjie; Wang, Wenjun; Ma, Kai; Yin, Zheng

    2016-09-01

    A simple and efficient bioanalytical method for simultaneous determination of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and its active metabolite carbamazepine 10,11-epoxide (CBZE) in human plasma using online solid phase extraction (SPE)-liquid chromatography (LC) coupled with high resolution mass spectrum (HRMS) under targeted MS/MS (t-MS(2)) analysis mode has been developed. The procedure integrated an automated sample clean-up of human plasma by Oasis®HLB SPE cartridge, a separation by ZORBAX SB-C18 analysis column, and a quantification by Q-Exactive Hybrid Quadrupole-Orbitrap. The total running time was 13min. The lower limit of quantification (LLOQ) of PB, PHT, CBZ, and CBZE were 0.008, 0.008, 0.0016 and 0.0016μgmL(-1) respectively and the linearities were in the range of 0.008-2.500, 0.008-2.500, 0.0016-0.500 and 0.0016-0.500μgmL(-1) respectively. The mean recovery was between 91.82% and 108.27% and the matrix effect was between 93.29% and 102.09%. The relative standard deviations of interday and intraday were less than 6.41%. The method has been successfully applied in therapeutic drug monitoring (TDM) of four Chinese epilepsy patients. This fully automated, simple, sensitive and reliable online-SPE-LC-HRMS/MS method serves well for TDM of PB, PHT, CBZ and CBZE at clinics for either single or combination treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Influence of sodium lauryl sulfate and tween 80 on carbamazepine-nicotinamide cocrystal solubility and dissolution behaviour.

    Science.gov (United States)

    Li, Mingzhong; Qiao, Ning; Wang, Ke

    2013-10-11

    The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine-nicotinamide (CBZ-NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ-NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ-NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ-NIC cocrystal but they had totally opposite effects on the IDR of the CBZ-NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ-NIC cocrystal while Tween 80 decreased its IDR.

  3. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  4. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    International Nuclear Information System (INIS)

    Lozano, Valeria A.; Escandar, Graciela M.

    2013-01-01

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  5. Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO_2 mediated heterogeneous activation of peroxymonosulfate

    International Nuclear Information System (INIS)

    Ding, Yaobin; Tang, Hebin; Zhang, Shenghua; Wang, Songbo; Tang, Heqing

    2016-01-01

    Highlights: • CuFeO_2 microparticles were prepared by a microwave-assisted hydrothermal method. • CuFeO_2 microparticles efficiently catalyzed the activation of peroxymonosulfate. • Quenching experiments confirmed sulfate radicals as the major reactive radicals. • Carbamazepine was rapidly degraded by micro-CuFeO_2/peroxymonosulfate. • Feasibility of CuFeO_2/peroxymonosulfate was tested for treatment of actual water. - Abstract: Microscaled CuFeO_2 particles (micro-CuFeO_2) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO_2 was of pure phase and a rhombohedral structure with size in the range of 2.8 ± 0.6 μm. The micro-CuFeO_2 efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO_4·−), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO_2 was observed to be 6.9 and 25.3 times that of micro-Cu_2O and micro-Fe_2O_3, respectively. The enhanced activity of micro-CuFeO_2 for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO_2 can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu_2O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO_2 was effective in the studied actual aqueous environmental systems.

  6. Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO{sub 2} mediated heterogeneous activation of peroxymonosulfate

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yaobin, E-mail: yaobinding@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Tang, Hebin [College of Pharmacy, South-Central University for Nationalities, Wuhan 430074 (China); Zhang, Shenghua; Wang, Songbo [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Tang, Heqing, E-mail: tangheqing@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China)

    2016-11-05

    Highlights: • CuFeO{sub 2} microparticles were prepared by a microwave-assisted hydrothermal method. • CuFeO{sub 2} microparticles efficiently catalyzed the activation of peroxymonosulfate. • Quenching experiments confirmed sulfate radicals as the major reactive radicals. • Carbamazepine was rapidly degraded by micro-CuFeO{sub 2}/peroxymonosulfate. • Feasibility of CuFeO{sub 2}/peroxymonosulfate was tested for treatment of actual water. - Abstract: Microscaled CuFeO{sub 2} particles (micro-CuFeO{sub 2}) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO{sub 2} was of pure phase and a rhombohedral structure with size in the range of 2.8 ± 0.6 μm. The micro-CuFeO{sub 2} efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO{sub 4}·−), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO{sub 2} was observed to be 6.9 and 25.3 times that of micro-Cu{sub 2}O and micro-Fe{sub 2}O{sub 3}, respectively. The enhanced activity of micro-CuFeO{sub 2} for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO{sub 2} can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu{sub 2}O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO{sub 2} was effective in the studied actual aqueous environmental systems.

  7. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Valeria A.; Escandar, Graciela M., E-mail: escandar@iquir-conicet.gov.ar

    2013-06-11

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  8. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-11-15

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD{sub 7} m{sup -3}d{sup -1}. Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k{sub biol}) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g{sub SS}{sup −1} d{sup −1}. Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k{sub biol} constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge.

  9. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    International Nuclear Information System (INIS)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-01-01

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD 7 m -3 d -1 . Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k biol ) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g SS −1 d −1 . Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k biol constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge

  10. Hedgehog Signalling in the Embryonic Mouse Thymus

    Directory of Open Access Journals (Sweden)

    Alessandro Barbarulo

    2016-07-01

    Full Text Available T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation.

  11. Ear embryonic rabdomiosarcoma. A case report

    International Nuclear Information System (INIS)

    Cueto, L.; Canabal, A.; Blanco, A.; Sabate, J.

    2002-01-01

    A case of embryonic rabdomiosarcoma in the ear of a 5-year-old girl who initially shows clinical symptoms of otitis media. The CT reveals a dense lesion of soft tissue which shows up slightly in the right external auditory channel. Also of interest were osteolytic areas in the petrous, clivus and zygomatic arch. A hypointensive lesion with marked enhancement after Gd-DPTA injection is observed. Discussed are the imaging methods used in the diagnosis of this tumor. (Author) 10 refs

  12. The Use of Embryonic Stem Cells

    OpenAIRE

    Corkery, Padraig

    2002-01-01

    Over the past year there has been great interest, optimism and anxiety in many societies about developments in the use of embryonic stem cells (ES cells). Within the scientific community there has been debate for some time on the merits and ethical implications of using ES cells. The discussion entered the public domain inthe decisive way during the past year when there were significant changes in legislation governing the use of such cells in Britain and the United States. These changes c...

  13. Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Vaibhav Shinde

    2016-04-01

    Full Text Available Background/Aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs under simulated microgravity within a fast-rotating clinostat (clinorotation and capture of microarray-based gene signatures. Methods: The differentiating mESCs were cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were used to capture genes that are deregulated by simulated microgravity and their impact on developmental biological processes. Results: The data analysis demonstrated that differentiation of mESCs in pipettes for 3 days resultet to early germ layer differentiation and then to the different somatic cell types after further 7 days of differentiation in the Petri dishes. Clinorotation influences differentiation as well as non-differentiation related biological processes like cytoskeleton related 19 genes were modulated. Notably, simulated microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and Dll1 are involved in heart morphogenesis as an acute response on day 3. If the stem cells were further cultivated under normal gravity conditions (1 g after clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2, Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well with a decreasing beating activity of the 10-days old embryoid bodies (EBs. Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions were modulated by simulated microgravity and by real microgravity in various reported studies. Simulated microgravity also deregulated genes belonging to the MAP kinase and focal dhesion signal transduction pathways. Conclusion: One of the most prominent biological processes affected by simulated microgravity was the process of cardiomyogenesis. The

  14. Do embryonic polar bodies commit suicide?

    Science.gov (United States)

    Fabian, Dušan; Čikoš, Štefan; Rehák, Pavol; Koppel, Juraj

    2014-02-01

    The extrusion and elimination of unnecessary gametic/embryonic material is one of the key events that determines the success of further development in all living organisms. Oocytes produce the first polar body to fulfill the maturation process just before ovulation, and release the second polar body immediately after fertilization. The aim of this study was to compile a physiological overview of elimination of polar bodies during early preimplantation development in mice. Our results show that three-quarters of the first polar bodies were lost even at the zygotic stage; the 4-cell stage embryos contained only one (second) polar body, and the elimination of second polar bodies proceeded continuously during later development. Both first and second polar bodies showed several typical features of apoptosis: phosphatidylserine redistribution (observed for the first time in the first polar body), specific DNA degradation, condensed nuclear morphology, and inability to exclude cationic dye from the nucleus during the terminal stage of the apoptotic process. Caspase-3 activity was recorded only in the second polar body. From the morphological point of view, mouse polar bodies acted very similarly to damaged embryonic cells which have lost contact with their neighboring blastomeres. In conclusion, polar bodies possess all the molecular equipment necessary for triggering and executing an active suicide process. Furthermore, similarly as in dying embryonic cells, stressing external conditions (culture in vitro) might accelerate and increase the incidence of apoptotic elimination of the polar bodies in embryos.

  15. Mechanical signaling coordinates the embryonic heartbeat

    Science.gov (United States)

    Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

    2016-01-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  16. Molecular fingerprinting of TGFbeta-treated embryonic maxillary mesenchymal cells.

    Science.gov (United States)

    Pisano, M M; Mukhopadhyay, P; Greene, R M

    2003-11-01

    The transforming growth factor-beta (TGF(beta)) family represents a class of signaling molecules that plays a central role in normal embryonic development, specifically in development of the craniofacial region. Members of this family are vital to development of the secondary palate where they regulate maxillary and palate mesenchymal cell proliferation and extracellular matrix synthesis. The function of this growth factor family is particularly critical in that perturbation of either process results in a cleft of the palate. While the cellular and phenotypic effects of TGF(beta) on embryonic craniofacial tissue have been extensively cataloged, the specific genes that function as downstream mediators of TGF(beta) in maxillary/palatal development are poorly defined. Gene expression arrays offer the ability to conduct a rapid, simultaneous assessment of hundreds to thousands of differentially expressed genes in a single study. Inasmuch as the downstream sequelae of TGF(beta) action are only partially defined, a complementary DNA (cDNA) expression array technology (Clontech's Atlas Mouse cDNA Expression Arrays), was utilized to delineate a profile of differentially expressed genes from TGF(beta)-treated primary cultures of murine embryonic maxillary mesenchymal cells. Hybridization of a membrane-based cDNA array (1178 genes) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either TGF(beta)-treated or vehicle-treated embryonic maxillary mesenchymal cells. Resultant phosphorimages were subject to AtlasImage analysis in order to determine differences in gene expression between control and TGF(beta)-treated maxillary mesenchymal cells. Of the 1178 arrayed genes, 552 (47%) demonstrated detectable levels of expression. Steady state levels of 22 genes were up-regulated, while those of 8 other genes were down-regulated, by a factor of twofold or greater in response to TGF(beta). Affected genes could be grouped into three general functional

  17. Culture conditions for bovine embryonic stem cell-like cells isolated from blastocysts after external fertilization

    OpenAIRE

    Jin, Muzi; Wu, Asga; Dorzhin, Sergei; Yue, Qunhua; Ma, Yuzhen; Liu, Dongjun

    2012-01-01

    Although isolation and characterization of embryonic stem cells have been successful in cattle, maintenance of bovine embryonic stem cells in culture remains difficult. In this study, we compared different methods of cell passaging, feeder cell layers and medium conditions for bovine embryonic stem cell-like cells. We found that a murine embryonic fibroblast feeder layer is more suitable for embryonic stem cell-like cells than bovine embryonic fibroblasts. When murine embryonic fibroblasts we...

  18. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: kanda@nihs.go.jp [Division of Pharmacology, National Institute of Health Sciences (Japan)

    2016-02-05

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  19. Embryonic stem cells and prospects for their use in regenerative medicine approaches to motor neurone disease.

    Science.gov (United States)

    Christou, Y A; Moore, H D; Shaw, P J; Monk, P N

    2007-10-01

    Human embryonic stem cells are pluripotent cells with the potential to differentiate into any cell type in the presence of appropriate stimulatory factors and environmental cues. Their broad developmental potential has led to valuable insights into the principles of developmental and cell biology and to the proposed use of human embryonic stem cells or their differentiated progeny in regenerative medicine. This review focuses on the prospects for the use of embryonic stem cells in cell-based therapy for motor neurone disease or amyotrophic lateral sclerosis, a progressive neurodegenerative disease that specifically affects upper and lower motor neurones and leads ultimately to death from respiratory failure. Stem cell-derived motor neurones could conceivably be used to replace the degenerated cells, to provide authentic substrates for drug development and screening and for furthering our understanding of disease mechanisms. However, to reliably and accurately culture motor neurones, the complex pathways by which differentiation occurs in vivo must be understood and reiterated in vitro by embryonic stem cells. Here we discuss the need for new therapeutic strategies in the treatment of motor neurone disease, the developmental processes that result in motor neurone formation in vivo, a number of experimental approaches to motor neurone production in vitro and recent progress in the application of stem cells to the treatment and understanding of motor neurone disease.

  20. Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development

    Directory of Open Access Journals (Sweden)

    Yandell Brian S

    2010-01-01

    Full Text Available Abstract Background Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development. Results Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development. Conclusions This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.

  1. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    International Nuclear Information System (INIS)

    Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

    2016-01-01

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  2. Human Embryonic Stem Cell Therapy in Crohn's Disease: A Case Report.

    Science.gov (United States)

    Shroff, Geeta

    2016-02-29

    Crohn's disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565,000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn's disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn's disease. A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn's disease.

  3. Deciphering the Mechanisms of Developmental Disorders (DMDD: a new programme for phenotyping embryonic lethal mice

    Directory of Open Access Journals (Sweden)

    Timothy Mohun

    2013-05-01

    International efforts to test gene function in the mouse by the systematic knockout of each gene are creating many lines in which embryonic development is compromised. These homozygous lethal mutants represent a potential treasure trove for the biomedical community. Developmental biologists could exploit them in their studies of tissue differentiation and organogenesis; for clinical researchers they offer a powerful resource for investigating the origins of developmental diseases that affect newborns. Here, we outline a new programme of research in the UK aiming to kick-start research with embryonic lethal mouse lines. The ‘Deciphering the Mechanisms of Developmental Disorders’ (DMDD programme has the ambitious goal of identifying all embryonic lethal knockout lines made in the UK over the next 5 years, and will use a combination of comprehensive imaging and transcriptomics to identify abnormalities in embryo structure and development. All data will be made freely available, enabling individual researchers to identify lines relevant to their research. The DMDD programme will coordinate its work with similar international efforts through the umbrella of the International Mouse Phenotyping Consortium [see accompanying Special Article (Adams et al., 2013] and, together, these programmes will provide a novel database for embryonic development, linking gene identity with molecular profiles and morphology phenotypes.

  4. p53 dependent apoptotic cell death induces embryonic malformation in Carassius auratus under chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Paramita Banerjee Sawant

    Full Text Available Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD, leading to embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia induced the early expression of pro-apoptotic/tumor suppressor p53 and concomitant expression of the cell death molecule, caspase-3, leading to high level of DNA damage and cell death in hypoxic embryos, as compared to normoxic ones. As a result, the former showed delayed 4 and 64 celled stages and a delay in appearance of epiboly stage. Expression of p53 efficiently switched off expression of the anti-apoptotic Bcl-2 during the initial 12 hours post fertilization (hpf and caused embryonic cell death. However, after 12 hours, simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl-2, caused uncontrolled cell proliferation and prevented essential programmed cell death (PCD, ultimately resulting in significant (p<0.05 embryonic malformation up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12 hpf may have been due to downregulation of p53 abundance, which in turn has an influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able to show for the first time and propose that hypoxia induced downregulation of p53 beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation, causing malformation in gold fish embryos.

  5. Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish

    OpenAIRE

    Xiang, Fan; Hagos, Engda G.; Xu, Bo; Sias, Christina; Kawakami, Koichi; Burdine, Rebecca D.; Dougan, Scott T.

    2007-01-01

    In many vertebrates, extra-embryonic tissues are important signaling centers that induce and pattern the germ layers. In teleosts, the mechanism by which the extra-embryonic yolk syncytial layer (YSL) patterns the embryo is not understood. Although the Nodal-related protein Squint is expressed in the YSL, its role in this tissue is not known. We generated a series of stable transgenic lines with GFP under the control of squint genomic sequences. In all species, nodal-related genes induce thei...

  6. Isolation of a primate embryonic stem cell line.

    OpenAIRE

    Thomson, J A; Kalishman, J; Golos, T G; Durning, M; Harris, C P; Becker, R A; Hearn, J P

    1995-01-01

    Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. Here we report the derivation of a cloned cell line (R278.5) from a rhesus monkey blastocyst that remains undifferentiated in continuous passage for > 1 year, maintains a normal XY karyotype, and expresses the cell surface markers (alkaline phosphatase, stage-specific embryonic antigen 3, st...

  7. Kinetic study of photocatalytic degradation of carbamazepine, clofibric acid, iomeprol and iopromide assisted by different TiO2 materials--determination of intermediates and reaction pathways.

    Science.gov (United States)

    Doll, Tusnelda E; Frimmel, Fritz H

    2004-02-01

    The light-induced degradation of clofibric acid, carbamazepine, iomeprol and iopromide under simulated solar irradiation has been investigated in aqueous solutions suspended with different TiO2 materials (P25 and Hombikat UV100). Kinetic studies showed that P25 had a better photocatalytic activity for clofibric acid and carbamazepine than Hombikat UV100. For photocatalytic degradation of iomeprol Hombikat UV100 was more suitable than P25. The results can be explained by the higher adsorption capacity of Hombikat UV100 for iomeprol. The study also focuses on the identification and quantification of possible degradation products. The degradation process was monitored by determination of sum parameters and inorganic ions. In case of clofibric acid various aromatic and aliphatic degradation products have been identified and quantified. A possible multi-step degradation scheme for clofibric acid is proposed. This study proves the high potential of the photocatalytic oxidation process to transform and mineralize environmentally relevant pharmaceuticals and contrast media in water.

  8. Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish

    International Nuclear Information System (INIS)

    Raldua, Demetrio; Andre, Michele; Babin, Patrick J.

    2008-01-01

    Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Treatment with micromolar concentrations of clofibrate or gemfibrozil induced an embryonic malabsorption syndrome (EMS) with very little yolk consumption, resulting in small-sized larvae. This effect was reversible on removing the drug from the water. Clofibrate delayed hatching time and decreased the amount of oil red O lipid staining in the vasculature. It also induced higher density, round-shaped neuromuscular junctions associated with disorganization and less striation of muscular fibers, and pericardial edema, as well as impairing thyroid gland morphogenesis. acox1, apoa1 and mtp hybridization transcript signals were not affected in the yolk syncytial layer (YSL) after clofibrate exposure. Di-(2-ethylhexyl)-phthalate did not slow down yolk resorption, whereas brefeldin A induced EMS. These findings suggest that the inhibition of yolk sac resorption on exposure to fibrate is not at a pre-translational level or peroxisome proliferator-activated receptor alpha dependent and may be due to an inhibition of the YSL constitutive cell secretion. The effects of fibrates and the potential bioconcentration in eggs as well as the additive action of structurally related toxicants warrant an evaluation of the developmental impact of these compounds after long-term exposure at environmentally relevant concentrations. Fibrate-induced EMS in zebrafish seems useful for studying the morphogenetic consequences of impaired nutrient availability during the early stages of vertebrate development

  9. Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube

    NARCIS (Netherlands)

    Fijnvandraat, Arnoud C.; van Ginneken, Antoni C. G.; de Boer, Piet A. J.; Ruijter, Jan M.; Christoffels, Vincent M.; Moorman, Antoon F. M.; Lekanne Deprez, Ronald H.

    2003-01-01

    OBJECTIVE: After formation of the linear heart tube a chamber-specific program of gene expression becomes active that underlies the formation of the chamber myocardium. To assess whether this program is recapitulated in in vitro differentiated embryonic stem cells, we performed qualitative and

  10. A novel disposable electrochemical sensor for determination of carbamazepine based on Fe doped SnO{sub 2} nanoparticles modified screen-printed carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Lavanya, N. [Department of Biosensors and Bioelectronics, Alagappa University, Karaikudi 630003, TN (India); Department of Electronic Engineering, Chemistry and Materials Engineering, University of Messina, Messina 98166 (Italy); Sekar, C., E-mail: Sekar2025@gmail.com [Department of Biosensors and Bioelectronics, Alagappa University, Karaikudi 630003, TN (India); Ficarra, S.; Tellone, E. [Department of Chemical Sciences, University of Messina, Messina 98166 (Italy); Bonavita, A.; Leonardi, S.G.; Neri, G. [Department of Electronic Engineering, Chemistry and Materials Engineering, University of Messina, Messina 98166 (Italy)

    2016-05-01

    An effective strategy to fabricate a novel disposable screen printing carbon electrode modified by iron doped tin dioxide nanoparticles for carbamazepine (CBZ) detection has been developed. Fe–SnO{sub 2} (Fe = 0 to 5 wt.%) NPs were synthesized by a simple microwave irradiation method and assessed for their structural and morphological changes due to Fe doping into SnO{sub 2} matrix by X-ray diffraction and scanning and transmission electron microscopy. The electrochemical behaviour of carbamazepine at the Fe–SnO{sub 2} modified screen printed carbon electrode (SPCE) was investigated by cyclic voltammetry and square wave voltammetry. Electron transfer coefficient α (0.63) and electron transfer rate constant k{sub s} (0.69 s{sup −1}) values of the 5 wt.% Fe–SnO{sub 2} modified SPCE indicate that the diffusion controlled process takes place on the electrode surface. The fabricated sensor displayed a good electrooxidation response towards the detection of CBZ at a lower oxidation potential of 0.8 V in phosphate buffer solution at pH 7.0. Under the optimal conditions, the sensor showed fast and sensitive current response to CBZ over a wide linear range of 0.5–100 μM with a low detection limit of 92 nM. Furthermore, the practical application of the modified electrode has been investigated by the determination of CBZ in pharmaceutical products using standard addition method. - Highlights: • A novel mediator-free disposable screen printed carbon electrode has been fabricated based on Fe- SnO{sub 2} nanoparticles for determination of carbamazepine • The Fe-SnO{sub 2}/SPCE showed wide linear range (0.5–100 μM), low detection limit (92 nM), high sensitivity, good stability and reproducibility. • The carbamazepine sensor was successfully applied to the analysis of pharmaceutical products with satisfactory recoveries.

  11. Effects of oxidative stress on human embryonic stem cells; global gene expression, advanced glycation end products and NEDD1 levels

    NARCIS (Netherlands)

    Barandalla Sobrados, M.

    2017-01-01

    A number of unfavorable conditions can affect the development of the early embryo inducing oxidative stress both in vivo, for instance in gestational diabetes, and in vitro, when embryos are derived from Assisted Reproductive Technologies (ART). Human Embryonic Stem Cells (hESCs) potentially offer a

  12. Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

    Directory of Open Access Journals (Sweden)

    Chen Qian

    Full Text Available Platelet-derived growth factor receptor alpha (PDGFRα is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures.To address the temporal requirement of Pdgfra in embryonic development.We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies.Current study showed that (i conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5 resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives.Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b if mutations / sequence variations of these regulatory elements cause these anomalies.

  13. Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues.

    Science.gov (United States)

    Van Herck, Stijn L J; Geysens, Stijn; Bald, Edward; Chwatko, Grazyna; Delezie, Evelyne; Dianati, Elham; Ahmed, R G; Darras, Veerle M

    2013-07-01

    Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T₄) content but an increase in thyroidal 3,5,3'-triiodothyronine (T₃) content. This resulted in normal T₃ levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T₄ availability was only moderately affected in embryos. Peripheral T₃ levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T₃ content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T₃ content, which is reduced throughout the embryonic development period.

  14. Composted biosolids and treated wastewater as sources of pharmaceuticals and personal care products for plant uptake: A case study with carbamazepine.

    Science.gov (United States)

    Ben Mordechay, Evyatar; Tarchitzky, Jorge; Chen, Yona; Shenker, Moshe; Chefetz, Benny

    2018-01-01

    Irrigation with treated wastewater (TWW) and application of biosolids to arable land expose the agro-environment to pharmaceuticals and personal care products (PPCPs) which can be taken up by crops. In this project, we studied the effect of a carrier medium (e.g., biosolids and TWW) on plant (tomato, wheat and lettuce) uptake, translocation and metabolism of carbamazepine as a model for non-ionic PPCPs. Plant uptake and bioconcentration factors were significantly lower in soils amended with biosolids compared to soils irrigated with TWW. In soils amended with biosolids and irrigated with TWW, the bioavailability of carbamazepine for plant uptake was moderately decreased as compared to plants grown in soils irrigated with TWW alone. While TWW acts as a continuous source of PPCPs, biosolids act both as a source and a sink for these compounds. Moreover, it appears that decomposition of the biosolids in the soil after amendment enhances their adsorptive properties, which in turn reduces the bioavailability of PPCPs in the soil environment. In-plant metabolism of carbamazepine was found to be independent of environmental factors, such as soil type, carrier medium, and absolute amount implemented to the soil, but was controlled by the total amount taken up by the plant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Carbamazepine degradation using a N-doped TiO_2 coated photocatalytic membrane reactor: Influence of physical parameters

    International Nuclear Information System (INIS)

    Horovitz, Inna; Avisar, Dror; Baker, Mark A.; Grilli, Rossana; Lozzi, Luca; Di Camillo, Daniela; Mamane, Hadas

    2016-01-01

    Highlights: • UV–vis N-doped TiO_2 was deposited by sol-gel onto Al_2O_3 microfiltration membranes. • Coating decreased permeability by 50 and 12% for 200- and 800-nm Al_2O_3 membranes. • Flow through membrane results in higher reaction rates compared to flow on top. • Higher vis photocatalytic activity for N-doped TiO_2 vs. non-doped TiO_2 membranes. • Mass transfer is a critical parameter for the design of immobilized PMR. - Abstract: Commercial α-Al_2O_3 photocatalytic membranes with a pore size of 200 and 800-nm were coated with N-doped TiO_2 photocatalytic film using a sol-gel technique for concurrent bottom-up filtration and photocatalytic oxidation. X-ray diffraction confirmed that the deposited N-doped TiO_2 films are in the form of anatase with 78–84% coverage of the membrane surface. The concentration of N found by X-ray photoelectron spectroscopy was in the range of 0.3–0.9 atomic percentage. Membrane permeability after coating decreased by 50% and 12% for the 200- and 800-nm membrane substrates, respectively. The impact of operational parameters on the photocatalytic activity (PCA) of the N-doped TiO_2-coated membranes was examined in a laboratory flow cell based on degradation of the model micropollutant carbamazepine, using a solar simulator as the light source. The significant gap in degradation rate between flow through the membrane and flow on the surface of the membrane was attributed both to the hydraulic effect and in-pore PCA. N-doped TiO_2-coated membranes showed enhanced activity for UV wavelengths, in addition to activity under visible light. Experiments of PCA under varying flow rates concluded that the process is in the mass-transfer control regime. Carbamazepine removal rate increased with temperature, despite the decrease in dissolved oxygen concentration.

  16. Carbamazepine degradation using a N-doped TiO{sub 2} coated photocatalytic membrane reactor: Influence of physical parameters

    Energy Technology Data Exchange (ETDEWEB)

    Horovitz, Inna [School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); The Hydro-Chemistry Laboratory, Faculty of Geography and the Environment, Tel Aviv University, Tel Aviv 69978 (Israel); Avisar, Dror [The Hydro-Chemistry Laboratory, Faculty of Geography and the Environment, Tel Aviv University, Tel Aviv 69978 (Israel); Baker, Mark A.; Grilli, Rossana [The Surface Analysis Laboratory, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom); Lozzi, Luca; Di Camillo, Daniela [Department of Physical and Chemical Sciences, University of L' Aquila, Via Vetoio, I-67100 L' Aquila (Italy); Mamane, Hadas, E-mail: hadasmg@post.tau.ac.il [School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel)

    2016-06-05

    Highlights: • UV–vis N-doped TiO{sub 2} was deposited by sol-gel onto Al{sub 2}O{sub 3} microfiltration membranes. • Coating decreased permeability by 50 and 12% for 200- and 800-nm Al{sub 2}O{sub 3} membranes. • Flow through membrane results in higher reaction rates compared to flow on top. • Higher vis photocatalytic activity for N-doped TiO{sub 2} vs. non-doped TiO{sub 2} membranes. • Mass transfer is a critical parameter for the design of immobilized PMR. - Abstract: Commercial α-Al{sub 2}O{sub 3} photocatalytic membranes with a pore size of 200 and 800-nm were coated with N-doped TiO{sub 2} photocatalytic film using a sol-gel technique for concurrent bottom-up filtration and photocatalytic oxidation. X-ray diffraction confirmed that the deposited N-doped TiO{sub 2} films are in the form of anatase with 78–84% coverage of the membrane surface. The concentration of N found by X-ray photoelectron spectroscopy was in the range of 0.3–0.9 atomic percentage. Membrane permeability after coating decreased by 50% and 12% for the 200- and 800-nm membrane substrates, respectively. The impact of operational parameters on the photocatalytic activity (PCA) of the N-doped TiO{sub 2}-coated membranes was examined in a laboratory flow cell based on degradation of the model micropollutant carbamazepine, using a solar simulator as the light source. The significant gap in degradation rate between flow through the membrane and flow on the surface of the membrane was attributed both to the hydraulic effect and in-pore PCA. N-doped TiO{sub 2}-coated membranes showed enhanced activity for UV wavelengths, in addition to activity under visible light. Experiments of PCA under varying flow rates concluded that the process is in the mass-transfer control regime. Carbamazepine removal rate increased with temperature, despite the decrease in dissolved oxygen concentration.

  17. File list: Oth.Emb.10.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.10.AllAg.Embryonic_palates mm9 TFs and others Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.10.AllAg.Embryonic_palates.bed ...

  18. File list: Oth.Emb.20.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Oth.Emb.50.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.50.AllAg.Embryonic_palates mm9 TFs and others Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.50.AllAg.Embryonic_palates.bed ...

  20. File list: Pol.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.AllAg.Embryonic_palates mm9 RNA polymerase Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.AllAg.Embryonic_palates.bed ...

  1. File list: Pol.Emb.20.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.AllAg.Embryonic_palates mm9 RNA polymerase Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.AllAg.Embryonic_palates.bed ...

  2. File list: Oth.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.Embryonic_palates mm9 TFs and others Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Embryonic_palates.bed ...

  3. File list: Pol.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Unc.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Unc.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Pol.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Unc.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Unc.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. In utero exposure to benzene increases embryonic c-Myb and Pim-1 protein levels in CD-1 mice

    International Nuclear Information System (INIS)

    Wan, Joanne; Winn, Louise M.

    2008-01-01

    Benzene is a known human leukemogen, but its role as an in utero leukemogen remains controversial. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. We hypothesize that in utero exposure to benzene may cause leukemogenesis by affecting the embryonic c-Myb/Pim-1 signaling pathway and that this is mediated by oxidative stress. To investigate this hypothesis, pregnant CD-1 mice were treated with either 800 mg/kg of benzene or corn oil (i.p.) on days 10 and 11 of gestation and in some cases pretreated with 25 kU/kg of PEG-catalase. Phosphorylated and total embryonic c-Myb and Pim-1 protein levels were assessed using Western blotting and maternal and embryonic oxidative stress were assessed by measuring reduced to oxidized glutathione ratios. Our results show increased oxidative stress at 4 and 24 h after exposure, increased phosphorylated Pim-1 protein levels 4 h after benzene exposure, and increased Pim-1 levels at 24 and 48 h after benzene exposure. Embryonic c-Myb levels were elevated at 24 h after exposure. PEG-catalase pretreatment prevented benzene-mediated increases in embryonic c-Myb and Pim-1 protein levels, and benzene-induced oxidative stress. These results support a role for ROS in c-Myb and Pim-1 alterations after in utero benzene exposure

  11. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

  12. Pathways in pluripotency and differentiation of embryonic cells

    NARCIS (Netherlands)

    du Puy, L.

    2010-01-01

    Pluripotency - the potential to differentiate into derivatives of the three embryonic germ layers endoderm, ectoderm and mesoderm - is the main characteristic of embryonic stem (ES) cells. ES cells are derived from the inner cell mass (ICM) of a pre-implantation blastocyst and can self-renew

  13. Sono-photo-degradation of carbamazepine in a thin falling film reactor: Operation costs in pilot plant.

    Science.gov (United States)

    Expósito, A J; Patterson, D A; Monteagudo, J M; Durán, A

    2017-01-01

    The photo-Fenton degradation of carbamazepine (CBZ) assisted with ultrasound radiation (US/UV/H 2 O 2 /Fe) was tested in a lab thin film reactor allowing high TOC removals (89% in 35min). The synergism between the UV process and the sonolytic one was quantified as 55.2%. To test the applicability of this reactor for industrial purposes, the sono-photo-degradation of CBZ was also tested in a thin film pilot plant reactor and compared with a 28L UV-C conventional pilot plant and with a solar Collector Parabolic Compound (CPC). At a pilot plant scale, a US/UV/H 2 O 2 /Fe process reaching 60% of mineralization would cost 2.1 and 3.8€/m 3 for the conventional and thin film plant respectively. The use of ultrasound (US) produces an extra generation of hydroxyl radicals, thus increasing the mineralization rate. In the solar process, electric consumption accounts for a maximum of 33% of total costs. Thus, for a TOC removal of 80%, the cost of this treatment is about 1.36€/m 3 . However, the efficiency of the solar installation decreases in cloudy days and cannot be used during night, so that a limited flow rate can be treated. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Study of the intensification of solar photo-Fenton degradation of carbamazepine with ferrioxalate complexes and ultrasound.

    Science.gov (United States)

    Expósito, A J; Monteagudo, J M; Durán, A; San Martín, I; González, L

    2018-01-15

    The intensification of the solar photo-Fenton system with ferrioxalate photoactive complexes and ultrasound applied to the mineralization of 15mg/L carbamazepine aqueous solution (CBZ) was evaluated. The experiments were carried out in a solar compound parabolic collector (CPC) pilot plant reactor coupled to an ultrasonic processor. The dynamic behavior of hydroxyl radicals generated under the different studied reaction systems was discussed. The initial concentrations of hydrogen peroxide and ferrous/oxalic acid and pH were found to be the most significant variables (32.79%, 25.98% and 26.04%, respectively). Under the selected optimal conditions ([H 2 O 2 ] 0 =150mg/L; [Fe 2+ ] 0 =2.5mg/L/[(COOH) 2 ] 0 =12.1mg/L; pH=5) CBZ was fully degraded after 5min and 80% of TOC was removed using a solar photo-Fenton system intensified with ferrioxalate (SPFF). However, no improvement in the mineralization using SPFF process combined with ultrasound was observed. More mild pH conditions could be used in the SPFF system if compared to the traditional photo-Fenton (pH 3) acidic systems. Finally, a possible reaction pathway for the mineralization of CBZ by the SPFF system was proposed and therein discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Carbamazepine as a Possible Anthropogenic Marker in Water: Occurrences, Toxicological Effects, Regulations and Removal by Wastewater Treatment Technologies

    Directory of Open Access Journals (Sweden)

    Faisal I. Hai

    2018-01-01

    Full Text Available Carbamazepine (CBZ, a pharmaceutical compound, has been proposed as an anthropogenic marker to assess water quality due to its persistence in conventional treatment plants and widespread presence in water bodies. This paper presents a comprehensive literature review on sources and occurrences of CBZ in water bodies, as well as toxicological effects and regulations of the drug. Given the documented side effects of CBZ on the human body when taken medicinally, its careful monitoring in water is recommended. CBZ residues in drinking water may provide a pathway to embryos and infants via intrauterine exposure or breast-feeding, which may cause congenital malformations and/or neurodevelopmental problems over long term exposure. An in-depth technical assessment of the conventional and advanced treatment technologies revealed the inadequacy of the standalone technologies. Compared to conventional activated sludge and membrane bioreactor processes, effective removal of CBZ can be achieved by nanofiltration and reverse osmosis membranes. However, recent studies have revealed that harsh chemical cleaning, as required to mitigate membrane fouling, can often reduce the long-term removal efficiency. Furthermore, despite the efficient performance of activated carbon adsorption and advanced oxidation processes, a few challenges such as cost of chemicals and regeneration of activated carbon need to be carefully considered. The limitations of the individual technologies point to the advantages of combined and hybrid systems, namely, membrane bioreactor coupled with nanofiltration, adsorption or advanced oxidation process.

  16. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

    Science.gov (United States)

    McKee, P J; Blacklaw, J; Forrest, G; Gillham, R A; Walker, S M; Connelly, D; Brodie, M J

    1994-01-01

    1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction. PMID:8148215

  17. Efficacy and acceptability of oxcarbazepine vs. carbamazepine with betahistine mesilate tablets in treating vestibular paroxysmia: a retrospective review.

    Science.gov (United States)

    Yi, Chong; Wenping, Xiang; Hui, Xue; Xin, He; Xiue, Li; Jun, Zhang; Shangyong, Geng

    2016-06-01

    Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder that can cause acute short attacks of vertigo. This study aimed to compare the efficacy and acceptability of carbamazepine (CBZ), CBZ plus betahistine mesilate tablets (BMT) and oxcarbazepine (OXC) plus BMT in treating VP within 12 weeks. A retrospective analysis of data from 196 VP patients treated in our hospital was conducted. There were 73 patients receiving CBZ, 65 patients receiving CBZ+BMT and 58 patients receiving OXC+BMT. The frequency of vertigo, vertigo duration, vertigo score, response rate (RR) and side effects were compared between groups to assess efficacy and acceptability at the end of 12(th) week. After 12 weeks' treatment, the CBZ+BMT group had a greater reduction in the frequency of vertigo, vertigo duration and vertigo score than the other two groups. The RR was highest in the CBZ+BMT group, second in the OXC+BMT group and lowest in the CBZ group. The incidence of side-effects was highest in the CBZ group, second in the CBZ+BMT group and lowest in the OXC+BMT group. Two patients in the CBZ group were withdrawn. These results indicated that using BMT as an augmentation for CBZ or OXC might be a good choice in treating VP.

  18. In-line monitoring of cocrystallization process and quantification of carbamazepine-nicotinamide cocrystal using Raman spectroscopy and chemometric tools

    Science.gov (United States)

    Soares, Frederico L. F.; Carneiro, Renato L.

    2017-06-01

    A cocrystallization process may involve several molecular species, which are generally solid under ambient conditions. Thus, accurate monitoring of different components that might appear during the reaction is necessary, as well as quantification of the final product. This work reports for the first time the synthesis of carbamazepine-nicotinamide cocrystal in aqueous media with a full conversion. The reactions were monitored by Raman spectroscopy coupled with Multivariate Curve Resolution - Alternating Least Squares, and the quantification of the final product among its coformers was performed using Raman spectroscopy and Partial Least Squares regression. The slurry reaction was made in four different conditions: room temperature, 40 °C, 60 °C and 80 °C. The slurry reaction at 80 °C enabled a full conversion of initial substrates into the cocrystal form, using water as solvent for a greener method. The employment of MCR-ALS coupled with Raman spectroscopy enabled to observe the main steps of the reactions, such as drug dissolution, nucleation and crystallization of the cocrystal. The PLS models gave mean errors of cross validation around 2.0 (% wt/wt), and errors of validation between 2.5 and 8.2 (% wt/wt) for all components. These were good results since the spectra of cocrystals and the physical mixture of the coformers present some similar peaks.

  19. pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin cocrystals in aqueous media.

    Science.gov (United States)

    Alhalaweh, Amjad; Roy, Lilly; Rodríguez-Hornedo, Naír; Velaga, Sitaram P

    2012-09-04

    Cocrystals constitute an important class of pharmaceutical solids for their remarkable ability to modulate solubility and pH dependence of water insoluble drugs. Here we show how cocrystals of indomethacin-saccharin (IND-SAC) and carbamazepine-saccharin (CBZ-SAC) enhance solubility and impart a pH-sensitivity different from that of the drugs. IND-SAC exhibited solubilities 13 to 65 times higher than IND at pH values of 1 to 3, whereas CBZ-SAC exhibited a 2 to 10 times higher solubility than CBZ dihydrate. Cocrystal solubility dependence on pH predicted from mathematical models using cocrystal K(sp), and cocrystal component K(a) values, was in excellent agreement with experimental measurements. The cocrystal solubility increase relative to drug was predicted to reach a limiting value for a cocrystal with two acidic components. This limiting value is determined by the ionization constants of cocrystal components. Eutectic constants are shown to be meaningful indicators of cocrystal solubility and its pH dependence. The two contributions to solubility, cocrystal lattice and solvation, were evaluated by thermal and solubility determinations. The results show that solvation is the main barrier for the aqueous solubility of these drugs and their cocrystals, which are orders of magnitude higher than their lattice barriers. Cocrystal increase in solubility is thus a result of decreasing the solvation barrier compared to that of the drug. This work demonstrates the favorable properties of cocrystals and strategies that facilitate their meaningful characterization.

  20. Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs.

    Science.gov (United States)

    O'Brien, Laura E; Timmins, Peter; Williams, Adrian C; York, Peter

    2004-10-29

    The solid-state transformation of carbamazepine from form III to form I was examined by Fourier Transform Raman spectroscopy. Using a novel environmental chamber, the isothermal conversion was monitored in situ at 130 degrees C, 138 degrees C, 140 degrees C and 150 degrees C. The rate of transformation was monitored by taking the relative intensities of peaks arising from two CH bending modes; this approach minimised errors due to thermal artefacts and variations in power intensities or scattering efficiencies from the samples in which crystal habit changed from a characteristic prism morphology (form III) to whiskers (form I). The solid-state transformation at the different temperatures was fitted to various solid-state kinetic models of which four gave good fits, thus indicating the complexity of the process which is known to occur via a solid-gas-solid mechanism. Arrhenius plots from the kinetic models yielded activation energies from 344 kJ mol(-1) to 368 kJ mol(-1) for the transformation. The study demonstrates the value of a rapid in situ analysis of drug polymorphic type which can be of value for at-line in-process control.

  1. Figures of merit for the determination of the polymorphic purity of carbamazepine by infrared spectroscopy and multivariate calibration.

    Science.gov (United States)

    Braga, Jez Willian B; Poppi, Ronei Jesus

    2004-08-01

    Polymorphism is an important property in the quality control of pharmaceutical products. In this regard, partial least squares regression and the net analytical signal were used to build and validate a multivariate calibration model using diffuse reflectance infrared spectroscopy in the region of 900-1100 cm(-1) for the determination of the polymorphic purity of carbamazepine. Physical mixtures of the polymorphs were made by weight, from 80 to 100% (w/w) form III mixed with form I. Figures of merit, such as sensitivity, analytical sensitivity, selectivity, confidence limits, precision (mean, repeatability, intermediate), accuracy, and signal-to-noise ratio were calculated. Feasible results were obtained with maximum absolute error of 2% and an average error of 0.53%, indicating that the proposed methodology can be used by the pharmaceutical industry as an alternative to the X-ray diffraction (United States Pharmacopoeiamethod). Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2124-2134, 2004

  2. Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.

    Science.gov (United States)

    Djuris, Jelena; Ioannis, Nikolakakis; Ibric, Svetlana; Djuric, Zorica; Kachrimanis, Kyriakos

    2014-02-01

    This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate. Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate. © 2013 Royal Pharmaceutical Society.

  3. Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients

    NARCIS (Netherlands)

    Hartong, EGTM; Moleman, P; Hoogduin, CAL; Broekman, TG; Nolen, WA

    Background: Alternatives to lithium for prophylactic treatment of patients with bipolar affective disorders are increasingly being advocated. However, trials comparing lithium with alternatives are scarce and often biased. Method: We studied 94 patients with at least 2 episodes of bipolar disorder

  4. The periconception maternal cardiovascular risk profile influences human embryonic growth trajectories in IVF/ICSI pregnancies.

    Science.gov (United States)

    Wijnands, K P J; van Uitert, E M; Roeters van Lennep, J E; Koning, A H J; Mulders, A G M G J; Laven, J S E; Steegers, E A P; Steegers-Theunissen, R P M

    2016-06-01

    Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association? This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies. Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life. In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated. Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses. From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly

  5. Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells

    DEFF Research Database (Denmark)

    Pines, Alex; Kelstrup, Christian D; Vrouwe, Mischa G

    2011-01-01

    (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia...... rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view...

  6. Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo.

    Science.gov (United States)

    Tucker, D C; Torres, A

    1992-02-01

    To allow experimental manipulation of adrenal hormone and autonomic influences on developing myocardium without alteration of hemodynamic load, embryonic rat heart was cultured in the anterior eye chamber of an adult rat. Sympathetic innervation of embryonic day 12 heart grafts was manipulated by surgical sympathectomy of one eye chamber in each host rat. Adrenal hormone exposure was manipulated by host adrenal medullectomy (MEDX) in experiment 1 and by host adrenalectomy (ADX) in experiment 2. In experiment 1, whole heart grafts were larger in MEDX than in sham-operated hosts by 8 wk in oculo (6.14 +/- 0.71 vs. 5.09 +/- 0.69 mm2 with innervation intact and 7.97 +/- 2.07 vs. 3.09 +/- 0.63 mm2 with sympathetic innervation prevented). In experiment 2, host ADX increased growth of embryonic day 12 ventricles grafted into sympathectomized eye chambers (0.69 +/- 0.10 vs. 0.44 +/- 0.04 mm2) but did not affect growth of grafts in intact eye chambers (0.85 +/- 0.09 vs. 1.05 +/- 0.15 mm2). Corticosterone replacement (4 mg/day) entirely reversed the effect of host ADX on graft growth (superior cervical ganglionectomy, 0.47 +/- 0.03 mm2; intact eye chambers, 0.90 +/- 0.91 mm2). Beating rate of grafts was not affected by adrenal hormone manipulations. These experiments indicate that the compromised growth of embryonic heart grafts placed in sympathectomized eye chambers requires exposure to adult levels of glucocorticoids during the early days after grafting. These results suggest that interactions between neural and hormonal stimulation influence cardiac growth in the in oculo culture system and during normal development.

  7. Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies

    DEFF Research Database (Denmark)

    Wright, A; Andrews, N; Bardsley, K

    2011-01-01

    The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state...... of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment....... and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range...

  8. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  9. Epigenetic control of embryonic stem cell fate

    DEFF Research Database (Denmark)

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    Embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and are pluripotent, as they are able to differentiate into all cell types of the adult organism. Once established, the pluripotent ES cells can be maintained under defined culture conditions, but can also...... be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...... the molecular switches that regulate ES cell self-renewal versus differentiation can provide insights into the nature of the pluripotent state and enhance the potential use of these cells in therapeutic applications. Here, we review the latest models for how changes in chromatin methylation can modulate ES cell...

  10. Embryonic stem cells in pig and cattle

    DEFF Research Database (Denmark)

    Maddox-Hyttel, Poul; Wolf, Xenia Asbæk; Rasmussen, Mikkel Aabech

    2007-01-01

    Porcine and bovine cell lines derived from the inner cell mass (ICM) or epiblasts of blastocysts have been maintained over extended periods of time and characterized by morphology, identification of some stem cell markers and, in few cases, by production of chimaeric offspring. However, germ line...... transmission in chimaeras has never been obtained. Due to this incomplete characterization of the cell lines, the expression embryonic stem (ES)-like cells is presently used in pig and cattle. The ICM or epiblast can be isolated from the blastocyst by whole blastocyst culture, mechanical isolation......, or immunosurgery, and they are generally cultured on feeder cells. The resulting ES-like cells may be differentiated in vivo by chimaera and teratoma formation or in vitro by embryoid body formation and monolayer induction. It is likely that more well characterized and stable porcine and bovine ES cell lines...

  11. Human embryonic stem cells and microenvironment

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2014-09-01

    Full Text Available Human embryonic stem cells (hESCs possess a great potential in the field of regenerative medicine by their virtue of pluripotent potential with indefinite proliferation capabilities. They can self renew themselves and differentiate into three embryonic germ layers. Although they are conventionally grown on mitotically inactivated mouse feeder cells, there are in vitro culture systems utilizing feeder cells of human origin in order to prevent cross-species contamination. Recently established in vitro culture systems suggested that direct interaction with feeder cells is not necessary but rather attachment to a substrate is required to ensure long-term, efficient hESC culture in vitro. This substrate is usually composed of a mixture of extracellular matrix components representing in vivo natural niche. In hESC biology, the mechanism of interaction of hESCs with extracellular matrix molecules remained insufficiently explored area of research due to their transient nature of interaction with the in vivo niche. However, an in vitro culture system established using extracellular matrix molecules may provide a safer alternative to culture systems with feeder cells while paving the way to Good Manufacturing Practice-GMP production of hESCs for therapeutic purposes. Therefore, it is essential to study the interaction of extracellular matrix molecules with hESCs in order to standardize in vitro culture systems for large-scale production of hESCs in a less labor-intensive way. This would not only provide valuable information regarding the mechanisms that control pluripotency but also serve to dissect the molecular signaling pathways of directed differentiation for prospective therapeutic applications in the future. J Clin Exp Invest 2014; 5 (3: 486-495

  12. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  13. In vivo and in vitro evaluation of the mutagenic potential of carbamazepine: does melatonin have anti-mutagenic activity?

    Science.gov (United States)

    Awara, W M; El-Gohary, M; El-Nabi, S H; Fadel, W A

    1998-01-16

    The mutagenic potential of carbamazepine (CBZ) therapy has been evaluated both in vivo and in vitro. Analysis of chromosome aberrations (CA), sister chromatid exchanges (SCEs), mitotic and proliferation indices (PRI) were performed. The in vivo study was carried out on 30 patients with idiopathic epilepsy end undergoing treatment with CBZ for different periods starting from 6 months up to 15 years. Plasma CBZ levels were also determined for each patient. The results showed that the total CA and SCEs were significantly increased in CBZ-treated patients. There was no significant correlation between CA and either duration of treatment or the plasma CBZ levels for each patient. The mitotic and proliferation indices were found to be slightly but non-significantly decreased compared to control values. On the other hand, in vitro analysis showed a significant dose-dependent increase in CA and SCEs in human lymphocyte cultures treated with CBZ (4-12 microg/ml). The mitotic and proliferation indices were also found to be decreased but only significantly in case of high doses of CBZ (12 microg/ml). Pretreatment of human lymphocytes with melatonin (0.5 mM) exhibited a significant decrease in the frequencies of CBZ-induced CA and SCEs as compared with non-treated cultures. The depressed mitotic and proliferation indices were also found to be improved in cultures pretreated with melatonin. In conclusion, these observations suggest that CBZ monotherapy may lead to chromosome damaging effects (genotoxic) and the use of melatonin as anti-mutagenic agent for human protection against CBZ-induced chromosome damage should be considered.

  14. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide.

    Science.gov (United States)

    Hebeisen, Simon; Pires, Nuno; Loureiro, Ana I; Bonifácio, Maria João; Palma, Nuno; Whyment, Andrew; Spanswick, David; Soares-da-Silva, Patrício

    2015-02-01

    This study aimed at evaluating the effects of eslicarbazepine, carbamazepine (CBZ), oxcarbazepine (OXC) and lacosamide (LCM) on the fast and slow inactivated states of voltage-gated sodium channels (VGSC). The anti-epileptiform activity was evaluated in mouse isolated hippocampal slices. The anticonvulsant effects were evaluated in MES and the 6-Hz psychomotor tests. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, CBZ, OXC and LCM on sodium channels endogenously expressed in N1E-115 mouse neuroblastoma cells. CBZ and eslicarbazepine exhibit similar concentration dependent suppression of epileptiform activity in hippocampal slices. In N1E-115 mouse neuroblastoma cells, at a concentration of 250 μM, the voltage dependence of the fast inactivation was not influenced by eslicarbazepine, whereas LCM, CBZ and OXC shifted the V0.5 value (mV) by -4.8, -12.0 and -16.6, respectively. Eslicarbazepine- and LCM-treated fast-inactivated channels recovered similarly to control conditions, whereas CBZ- and OXC-treated channels required longer pulses to recover. CBZ, eslicarbazepine and LCM shifted the voltage dependence of the slow inactivation (V0.5, mV) by -4.6, -31.2 and -53.3, respectively. For eslicarbazepine, LCM, CBZ and OXC, the affinity to the slow inactivated state was 5.9, 10.4, 1.7 and 1.8 times higher than to the channels in the resting state, respectively. In conclusion, eslicarbazepine did not share with CBZ and OXC the ability to alter fast inactivation of VGSC. Both eslicarbazepine and LCM reduce VGSC availability through enhancement of slow inactivation, but LCM demonstrated higher interaction with VGSC in the resting state and with fast inactivation gating. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. N-Doped TiO2-Coated Ceramic Membrane for Carbamazepine Degradation in Different Water Qualities

    Science.gov (United States)

    Luster, Enbal; Avisar, Dror; Horovitz, Inna; Lozzi, Luca; Baker, Mark A.; Grilli, Rossana; Mamane, Hadas

    2017-01-01

    The photocatalytic degradation of the model pollutant carbamazepine (CBZ) was investigated under simulated solar irradiation with an N-doped TiO2-coated Al2O3 photocatalytic membrane, using different water types. The photocatalytic membrane combines photocatalysis and membrane filtration in a single step. The impact of each individual constituent such as acidity, alkalinity, dissolved organic matter (DOM), divalent cations (Mg2+ and Ca2+), and Cl− on the degradation of CBZ was examined. CBZ in water was efficiently degraded by an N-doped TiO2-coated Al2O3 membrane. However, elements added to the water, which simulate the constituents of natural water, had an impact on the CBZ degradation. Water alkalinity inhibited CBZ degradation mostly due to increase in pH while radical scavenging by carbonate was more dominant at higher values (>200 mg/L as CaCO3). A negative effect of Ca2+ addition on photocatalytic degradation was found only in combination with phosphate buffer, probably caused by deposition of CaHPO4 or CaHPO4·2H2O on the catalyst surface. The presence of Cl− and Mg2+ ions had no effect on CBZ degradation. DOM significantly inhibited CBZ degradation for all tested background organic compounds. The photocatalytic activity of N-doped TiO2-coated Al2O3 membranes gradually decreased after continuous use; however, it was successfully regenerated by 0.1% HCl chemical cleaning. Nevertheless, dissolution of metals like Al and Ti should be monitored following acid cleaning. PMID:28758982

  16. Influence of UV dose on the UV/H2O2 process for the degradation of carbamazepine in wastewater.

    Science.gov (United States)

    Somathilake, Purnima; Dominic, John Albino; Achari, Gopal; Langford, Cooper H; Tay, Joo-Hwa

    2018-05-02

    This study evaluates the influence of UV dose on degradation of carbamazepine (CBZ) in wastewater under UV-C (λ = 254 nm) photolysis with and without H 2 O 2 . The rate of degradation of CBZ exhibited a direct dependence on the intensity of incident UV irradiation as the rate of degradation was observed to increase linearly (R 2  = 0.98) with UV intensity between 1.67 and 8.95 × 10 17 photons/s. More than 95% of the CBZ that spiked in wastewater rapidly degraded within 4 min with a first-order rate constant of 1.2 min -1 for an optimum H 2 O 2 dose of 100 mg/L. Bench-scale continuous flow reactor experiments also showed that CBZ degraded with first-order kinetics at a rate constant of 1.02 min -1 . The kinetic parameters obtained for a continuous bench-scale reactor were in good agreement with the relationships developed through batch experiments with only a marginal deviation of ± 6.5%. The relationship between UV intensity and CBZ degradation rate obtained in this study was extrapolated to the UV disinfection unit of a wastewater treatment plant to predict possible degradation of CBZ during UV disinfection. The addition of 100 mg/L of H 2 O 2 to the secondary-treated effluent entering the UV disinfection unit is predicted to achieve over 60% degradation of CBZ.

  17. Flow injection on-line oxidizing fluorometry coupled to dialysis sampling for the study of carbamazepine-protein binding

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Zhiqi [School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)]. E-mail: zqzhang@snnu.edu.cn; Liang Guoxi [School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)

    2005-04-22

    The mechanism of binding of carbamazepine (CBZ) with bovine serum albumin (BSA) has been investigated in vitro based on a new flow injection fluorometry coupled to the technique of dialysis sampling. The CBZ and BSA were mixed in different molar ratios in 0.050 mol L{sup -1} phosphate buffer (containing 0.9% NaCl), pH 7.4, and incubated at 37 {+-} 0.5 deg. C in a water bath. The dialysis sampler was utilized to sample free CBZ from mixed solution with a relative dialytic efficiency of 7.6%. Then the CBZ in dialysis solution was injected into carrier and on-line oxidized by lead dioxide solid-phase reactor into fluorescent product with a maximum excitation wavelength of 355 nm and a maximum emission wavelength of 478 nm. The fluorescence intensity measured was linear proportional with the concentration of free CBZ in mixed solution over the range of 1 x 10{sup -5} to 2 x 10{sup -4} mol L{sup -1} with the detection limit of 6 x 10{sup -6} mol L{sup -1}. According to the fluorescence measurement results from mixed solution, the association constant (K) estimated for CBZ-BSA binding and the number of the binding site (n) with Scatchard analysis were 1.08 x 10{sup 4} L mol{sup -1} and 0.94, respectively. Stern-Volmer plots indicated the presence of dynamic component in the quenching mechanism. The acting force was suggested to be mainly hydrophobic and the distance between the acceptor and donor was 3.12 nm. The estimated binding parameters agreed well with literature values.

  18. Modeling Raw Sewage Leakage and Transport in the Unsaturated Zone of Carbonate Aquifer Using Carbamazepine as an Indicator

    Science.gov (United States)

    Yakirevich, A.; Kuznetsov, M.; Livshitz, Y.; Gasser, G.; Pankratov, I.; Lev, O.; Adar, E.; Dvory, N. Z.

    2016-12-01

    Fast contamination of groundwater in karstic aquifers can be caused due to leaky sewers, for example, or overflow from sewer networks. When flowing through a karst system, wastewater has the potential to reach the aquifer in a relatively short time. The Western Mountain Aquifer (Yarkon-Taninim) of Israel is one of the country's major water resources. During late winter 2013, maintenance actions were performed on a central sewage pipe that caused raw sewage to leak into the creek located in the study area. The subsequent infiltration of sewage through the thick ( 100 m) fractured/karst unsaturated zone led to a sharp increase in contaminant concentrations in the groundwater, which was monitored in a well located 29 meters from the center of the creek. Carbamazepine (CBZ) was used as an indicator for the presence of untreated raw sewage and its quantification in groundwater. The ultimate research goal was to develop a mathematical model for quantifying flow and contaminant transport processes in the fractured-porous unsaturated zone and karstified groundwater system. A quasi-3D dual permeability numerical model, representing the 'vadose zone - aquifer' system, was developed by a series of 1D equations solved in variably-saturated zone and by 3D-saturated flow and transport equation in groundwater. The 1D and 3D equations were coupled at the moving phreatic surface. The model was calibrated and applied to a simulated water flow scenario and CBZ transport during and after the observed sewage leakage event. The results of simulation showed that after the leakage stopped, significant amounts of CBZ were retained in the porous matrix of the unsaturated zone below the creek. Water redistribution and slow recharge during the dry summer season contributed to elevated CBZ concentrations in the groundwater in the vicinity of the creek and tens of meters downstream. The resumption of autumn rains enhanced flushing of CBZ from the unsaturated zone and led to an increase in

  19. Second-order advantage with excitation-emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters.

    Science.gov (United States)

    Lozano, Valeria A; Escandar, Graciela M

    2013-06-11

    A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation-emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and quantification of 0.2 and 0.6 ng mL(-1) were respectively obtained. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Sorption of carbamazepine, 17α-ethinylestradiol, iopromide and trimethoprim to biomass involves interactions with exocellular polymeric substances.

    Science.gov (United States)

    Khunjar, Wendell O; Love, Nancy G

    2011-02-01

    The sorption of carbamazepine (CBZ), iopromide (IOP), trimethoprim (TMP) and 17α-ethinylestradiol (EE2) was evaluated using four biomass types (pure ammonia oxidizing bacterial culture, two heterotrophic enrichment cultures with varying levels of oxygenase activity, and a full-scale nitrifying activated sludge (NAS) culture). CBZ and IOP did not sorb to the four biomass types. EE2 did not sorb to the pure culture but sorbed significantly to the heterotrophic cultures and NAS. TMP sorbed to the heterotrophic cultures and NAS, and was not evaluated for the pure culture. Three floc characteristics (hydrophobicity, median particle size, organic matter content) correlated moderately well with the EE2 organic matter sorption coefficient (KOM,EE2). Zeta potential did not correlate well with KOM,EE2 but did with KOM,TMP, indicating that TMP sorption is more influenced by electrostatic factors than EE2. Once divalent cation-linked exocellular polymeric substances (EPS) were removed from flocs, EE2 and TMP sorption to the non-EPS (cellular) fraction decreased by approximately 50%. The correlation between KOM,EE2 for the non-EPS cellular fraction deteriorated while the correlation between KOM,TMP improved. EE2 seemed to sorb more strongly to EPS protein whereas TMP sorbed equally to polysaccharide and protein EPS. Attempts to develop predictive models were not successful. Pharmaceuticals that sorbed to biomass samples underwent biodegradation whereas those that did not sorb were not biodegraded, suggesting a relationship between sorption and pharmaceutical biotransformation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Elly Suk Hen [Division of Biology, California Institute of Technology, 1200 California Boulevard, Pasadena, CA 91125 (United States); Hui, Michelle Nga Yu; Lin Chunchi [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China); Cheng Shukhan [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China)], E-mail: bhcheng@cityu.edu.hk

    2008-05-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis.

  2. Resveratrol Enhances Self-Renewal of Mouse Embryonic Stem Cells.

    Science.gov (United States)

    Li, Na; Du, Zhaoyu; Shen, Qiaoyan; Lei, Qijing; Zhang, Ying; Zhang, Mengfei; Hua, Jinlian

    2017-07-01

    Resveratrol (RSV) has been shown to affect the differentiation of several types of stem cells, while the detailed mechanism is elusive. Here, we aim to investigate the function of RSV in self-renewal of mouse embryonic stem cells (ESCs) and the related mechanisms. In contrast with its reported roles, we found unexpectedly that differentiated ESCs or iPSCs treated by RSV would not show further differentiation, but regained a naïve pluripotency state with higher expressions of core transcriptional factors and with the ability to differentiate into all three germ layers when transplanted in vivo. In accordance with these findings, RSV also enhanced cell cycle progression of ESCs via regulating cell cycle-related proteins. Finally, enhanced activation of JAK/STAT3 signaling pathway and suppressed activation of mTOR were found essential in enhancing the self-renewal of ESCs by RSV. Our finding discovered a novel function of RSV in enhancing the self-renewal of ESCs, and suggested that the timing of treatment and concentration of RSV determined the final effect of it. Our work may contribute to understanding of RSV in the self-renewal maintenance of pluripotent stem cells, and may also provide help to the generation and maintenance of iPSCs in vitro. J. Cell. Biochem. 118: 1928-1935, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    International Nuclear Information System (INIS)

    Chow, Elly Suk Hen; Hui, Michelle Nga Yu; Lin Chunchi; Cheng Shukhan

    2008-01-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis

  4. Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells.

    Science.gov (United States)

    Lefevre, James G; Chiu, Han S; Combes, Alexander N; Vanslambrouck, Jessica M; Ju, Ali; Hamilton, Nicholas A; Little, Melissa H

    2017-03-15

    Human pluripotent stem cells, after directed differentiation in vitro , can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here, we investigate the timing and underlying mechanisms driving self-organisation after dissociation of the embryonic kidney using time-lapse imaging, high-resolution confocal analyses and mathematical modelling. Organotypic self-organisation sufficient for nephron initiation was observed within a 24 h period. This involved cell movement, with structure emerging after the clustering of ureteric epithelial cells, a process consistent with models of random cell movement with preferential cell adhesion. Ureteric epithelialisation rapidly followed the formation of ureteric cell clusters with the reformation of nephron-forming niches representing a later event. Disruption of P-cadherin interactions was seen to impair this ureteric epithelial cell clustering without affecting epithelial maturation. This understanding could facilitate improved regulation of patterning within organoids and facilitate kidney engineering approaches guided by cell-cell self-organisation. © 2017. Published by The Company of Biologists Ltd.

  5. Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death.

    Directory of Open Access Journals (Sweden)

    Magalie Vatin

    Full Text Available Recurrent spontaneous abortion (RSA is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (∼30%. Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.

  6. The zinc finger transcription factor 191 is required for early embryonic development and cell proliferation

    International Nuclear Information System (INIS)

    Li Jianzhong; Chen Xia; Yang Hua; Wang Shuiliang; Guo Baoyu; Yu Long; Wang Zhugang; Fu Jiliang

    2006-01-01

    Human zinc finger protein 191 (ZNF191/ZNF24) was cloned and characterized as a SCAN family member, which shows 94% identity to its mouse homologue zinc finger protein 191 (Zfp191). ZNF191 can specifically interact with an intronic polymorphic TCAT repeat (HUMTH01) in the tyrosine hydroxylase (TH) gene. Allelic variations of HUMTH01 have been stated to have a quantitative silencing effect on TH gene expression and to correlate with quantitative and qualitative changes in the binding by ZNF191. Zfp191 is widely expressed during embryonic development and in multiple tissues and organs in adult. To investigate the functions of Zfp191 in vivo, we have used homologous recombination to generate mice that are deficient in Zfp191. Heterozygous Zfp191 +/- mice are normal and fertile. Homozygous Zfp191 -/- embryos are severely retarded in development and die at approximately 7.5 days post-fertilization. Unexpectedly, in Zfp191 -/- and Zfp191 +/- embryos, TH gene expression is not affected. Blastocyst outgrowth experiments and the RNA interference-mediated knockdown of ZNF191 in cultured cells revealed an essential role for Zfp191 in cell proliferation. In further agreement with this function, no viable Zfp191 -/- cell lines were obtained by derivation of embryonic stem (ES) cells from blastocysts of Zfp191 +/- intercrosses or by forced homogenotization of heterozygous ES cells at high concentrations of G418. These data show that Zfp191 is indispensable for early embryonic development and cell proliferation

  7. Different concentrations of kaempferol distinctly modulate murine embryonic stem cell function.

    Science.gov (United States)

    Correia, Marcelo; Rodrigues, Ana S; Perestrelo, Tânia; Pereira, Sandro L; Ribeiro, Marcelo F; Sousa, Maria I; Ramalho-Santos, João

    2016-01-01

    Kaempferol (3,4',5,7-tetrahydroxyflavone) is a natural flavonoid with several beneficial and protective effects. It has been demonstrated that kaempferol has anticancer properties, particularly due to its effects on proliferation, apoptosis and the cell cycle. However, possible effects on pluripotent embryonic stem cell function have not yet been addressed. Embryonic stem cells have the ability to self-renew and to differentiate into all three germ layers with potential applications in regenerative medicine and in vitro toxicology. We show that exposure of murine embryonic stem cells (mESC) to high concentrations of kaempferol (200 μM) leads to decreased cell numbers, although the resulting smaller cell colonies remain pluripotent. However, lower concentrations of this compound (20 μM) increase the expression of pluripotency markers in mESCs. Mitochondrial membrane potential and mitochondrial mass are not affected, but a dose-dependent increase in apoptosis takes place. Moreover, mESC differentiation is impaired by kaempferol, which was not related to apoptosis induction. Our results show that low concentrations of kaempferol can be beneficial for pluripotency, but inhibit proper differentiation of mESCs. Additionally, high concentrations induce apoptosis and increase mitochondrial reactive oxygen species (ROS). Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Affects and Affect Consciousness

    Science.gov (United States)

    MONSEN, JON T.; EILERTSEN, DAG ERIK; MELGÅRD, TROND; ØDEGÅRD, PÅL

    1996-01-01

    Affect consciousness (AC) was operationalized as degrees of awareness, tolerance, nonverbal expression, and conceptual expression of nine specific affects. A semistructured interview (ACI) and separate scales were developed to assess these aspects of affect integration. Their psychometric properties were preliminarily explored by having 20 former psychiatric outpatients complete the interview. Concurrent validity was assessed by using DSM-III-R Axis I and II diagnoses, the Health-Sickness Rating Scale, SCL-90-R, and several indexes from the Minnesota Multiphasic Personality Inventory. Satisfactory interrater reliability and high levels of internal consistency supported the construct validity of the measure. Results suggest the most meaningful use of this instrument is in measuring specific affect and overall AC. Clinically, the ACI has provided highly specific and relevant qualitative data for use in planning psychotherapeutic interventions. PMID:22700292

  9. Probing Embryonic Stem Cell Autocrine and Paracrine Signaling Using Microfluidics

    Science.gov (United States)

    Przybyla, Laralynne; Voldman, Joel

    2012-07-01

    Although stem cell fate is traditionally manipulated by exogenously altering the cells' extracellular signaling environment, the endogenous autocrine and paracrine signals produced by the cells also contribute to their two essential processes: self-renewal and differentiation. Autocrine and/or paracrine signals are fundamental to both embryonic stem cell self-renewal and early embryonic development, but the nature and contributions of these signals are often difficult to fully define using conventional methods. Microfluidic techniques have been used to explore the effects of cell-secreted signals by controlling cell organization or by providing precise control over the spatial and temporal cellular microenvironment. Here we review how such techniques have begun to be adapted for use with embryonic stem cells, and we illustrate how many remaining questions in embryonic stem cell biology could be addressed using microfluidic technologies.

  10. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Jane

    2011-08-01

    Aug 1, 2011 ... In this study, the differentiation potential of chicken ES cells was investigated ... Key words: Chicken embryonic stem cells, in vitro, directional differentiation, .... synthesized by using the Revert Aid first strand cDNA synthesis kit.

  11. Graphene for enhanced embryonic stem cell photo-transfection efficiency

    CSIR Research Space (South Africa)

    Mthunzi, P

    2013-04-01

    Full Text Available Due to their pluripotency properties, embryonic stem (ES) cells possess great potential in regenerative therapy. Since reported a promising tissue engineering scaffold material, here, graphene is demonstrated to significantly improve the ES cell...

  12. Monoclonal antibodies to carcino-embryonic antigen

    International Nuclear Information System (INIS)

    Teh, Jinghee; McKenzie, I.F.C.

    1990-01-01

    With the aim of producing new MoAb to colorectal carcinoma, immunization with cell suspensions of a fresh colonic tumour was performed and MoAb 17C4 was obtained. To produce other MoAb to colon cancer, an immunization protocol using fresh tumour, colonic cell lines and sera from patients with colonic tumours was employed and resulted in MoAb JGT-13, LK-4 and XPX-13. MoAb I-1 and O-1 were raised against sera from patients with colon cancer to produce MoAb directed against circulating tumour associated antigens. The six antibodies gave a range of reactions with normal and malignant tissues, indicating that they most likely reacted with different epitopes. Thus, apart from the reactions of 17C4, LK-4 and XPX-13 with fresh and formalin-fixed granulocytes, none of the antibodies reacted with formalin-fixed normal tissues. Despite the apparent specificity of these MoAb for colon cancer, serum testing using MoAb gave similar results to carcino-embryonic antigen polyclonal antibodies, that is the MoAb gave no obvious advantage. 9 refs., 1 tab., 3 figs

  13. The epigenomics of embryonic stem cell differentiation.

    Science.gov (United States)

    Kraushaar, Daniel C; Zhao, Keji

    2013-01-01

    Embryonic stem cells (ESCs) possess an open and highly dynamic chromatin landscape, which underlies their plasticity and ultimately maintains ESC pluripotency. The ESC epigenome must not only maintain the transcription of pluripotency-associated genes but must also, through gene priming, facilitate rapid and cell type-specific activation of developmental genes upon lineage commitment. Trans-generational inheritance ensures that the ESC chromatin state is stably transmitted from one generation to the next; yet at the same time, epigenetic marks are highly dynamic, reversible and responsive to extracellular cues. Once committed to differentiation, the ESC epigenome is remodeled and resolves into a more compact chromatin state. A thorough understanding of the role of chromatin modifiers in ESC fate and differentiation will be important if they are to be used for therapeutic purposes. Recent technical advances, particularly in next-generation sequencing technologies, have provided a genome-scale view of epigenetic marks and chromatin modifiers. More affordable and faster sequencing platforms have led to a comprehensive characterization of the ESC epigenome and epigenomes of differentiated cell types. In this review, we summarize and discuss the recent progress that has highlighted the central role of histone modifications, histone variants, DNA methylation and chromatin modifiers in ESC pluripotency and ESC fate. We provide a detailed and comprehensive discussion of genome-wide studies that are pertinent to our understanding of mammalian development.

  14. Ovarian Embryonal Carcinoma in a Dog.

    Science.gov (United States)

    Banco, B; Ferrari, R; Stefanello, D; Groppetti, D; Pecile, A; Faverzani, S; Longo, M; Zani, D D; Ravasio, G; Caniatti, M; Grieco, V

    2017-11-01

    A 17-month-old female doberman pinscher was referred for an abdominal mass and ascites. Exploratory laparotomy revealed the presence of a large neoplastic mass replacing the right ovary and associated with multiple mesovarian, mesometrial and peritoneal nodules. An ovariohysterectomy was performed. Grossly, the tumour was soft and multilocular with large areas of haemorrhage and necrosis. Microscopically, it was infiltrative and composed of round and polygonal cells arranged respectively in solid sheets or forming distorted tubular structures separated by thick fibrovascular septae. Tubules contained necrotic debris, proteinaceous fluid or small endoluminal papillary structures. Marked cellular atypia, multiple neoplastic emboli and high mitotic count were observed. Immunohistochemically, the round cells uniformly expressed placental alkaline phosphatase, while the polygonal cells arranged in tubules and papillae expressed cytokeratin (CK) AE1/AE3 and CK7. A final diagnosis of metastasizing ovarian embryonal carcinoma (EC), a primitive germ cell tumour characterized by rudimentary epithelial differentiation was made. Canine ovarian EC should be considered as a differential diagnosis for undifferentiated aggressive ovarian tumours in young dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Retinol improves bovine embryonic development in vitro

    Directory of Open Access Journals (Sweden)

    Edwards J Lannett

    2004-12-01

    Full Text Available Abstract Retinoids are recognized as important regulators of vertebrate development, cell differentiation, and tissue function. Previous studies, performed both in vivo and in vitro, indicate that retinoids influence several reproductive events, including follicular development, oocyte maturation and early embryonic development. The present study evaluated in vitro effects of retinol addition to media containing maturing bovine oocytes and developing embryos in both a low oxygen atmosphere (7% and under atmospheric oxygen conditions (20%. In the first experiment, abbatoir collected bovine oocytes were matured in the presence or absence of varying concentrations of retinol. After a 22–24 hour maturation period the oocytes were fertilized, denuded 18 hours later and cultured in a modified synthetic oviductal fluid (mSOF in a humidified atmosphere at 38.5 degrees C, 5% CO2, 7% O2 and 88% N2. Cleavage rates did not differ among control and retinol-treated oocytes in all three experiments. Addition of 5 micromolar retinol to the maturation medium (IVM tended (p

  16. Targeting embryonic signaling pathways in cancer therapy.

    Science.gov (United States)

    Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

    2012-01-01

    The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

  17. ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

    OpenAIRE

    Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

    2010-01-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 di...

  18. Generation of hematopoietic lineage cells from embryonic like cells

    Directory of Open Access Journals (Sweden)

    Gholam Reza Khamisipour

    2014-10-01

    Full Text Available Background: Epigenetic reprogramming of somatic cells into embryonic stem cells has attracted much attention, because of the potential for stem cell transplantation and compatibility with recipient. However, the therapeutic application of either nuclear transfer or nuclear fusion of somatic cell has been hindered by technical complications as well as ethical objections. Recently, a new method is reported whereby ectopic expression of embryonic specific transcription factors was shown to induce fibroblasts to become embryonic like SCs (induced pluripotent stem cells. A major limitation of this method is the use of potentially harmful genome integrating viruses such as reto- or lentivirus. The main aim of this investigation was generation of human hematopoietic stem cells from induced fibroblasts by safe adenovectors carrying embryonically active genes. Material and Methods: Isolated fibroblasts from foreskin were expanded and recombinant adenoviruses carrying human Sox2, Oct4, Klf4, cMyc genes were added to culture. After formation of embryonic like colonies and cell expansion, they were transferred to embryonic media without bFGF, and embryoid bodies were cultured on stromal and non-stromal differentiation media for 14 days. Results: Expression of CD34 gene and antigenic markers, CD34, CD38 & CD133 in stromal culture showed significant difference with non-differentiation and non-stromal media. Conclusion: These findings show high hematopoietic differentiation rate of Adeno-iPS cells in stromal culture and no need to use growth factors. While, there was no difference between non-differentiation and non-stromal media.

  19. Periconceptional maternal one-carbon biomarkers are associated with embryonic development according to the Carnegie stages.

    Science.gov (United States)

    Parisi, F; Rousian, M; Koning, A H J; Willemsen, S P; Cetin, I; Steegers-Theunissen, R P M

    2017-03-01

    Is periconceptional maternal one-carbon (I-C) metabolism associated with embryonic morphological development in non-malformed ongoing pregnancies? Serum vitamin B12, red blood cell (RBC) folate and plasma total homocysteine (tHcy) are associated with embryonic development according to the Carnegie stages. Derangements in maternal I-C metabolism affect reproductive and pregnancy outcomes, as well as future health of the offspring. Between 2010 and 2014, women with singleton ongoing pregnancies were enrolled in a prospective periconceptional cohort study. A total of 234 pregnancies, including 138 spontaneous or IUI pregnancies with strict pregnancy dating and 96 pregnancies derived from IVF, ICSI or cryopreserved embryo transfer (IVF/ICSI pregnancies), underwent longitudinal transvaginal three-dimensional ultrasound (3D US) scans from 6+0 up to 10+2 weeks of gestation. Carnegie stages were defined using internal and external morphologic criteria in a virtual reality system. Maternal venous blood samples were collected at enrollment for serum vitamin B12, RBC folate and plasma tHcy assessment. Associations between biomarker concentrations and longitudinal Carnegie stages were investigated using linear mixed models. We performed a median of three 3D US scans per pregnancy (range 1-5) resulting in 600 good quality data sets for the Carnegie stage annotation (80.5%). Vitamin B12 was positively associated with embryonic development in the total study population (β = 0.001 (95% CI: 0.000; 0.002), P Carnegie stages only in IVF/ICSI pregnancies (β = 0.001 (95% CI: 0.0005; 0.0015), P < 0.05). In this group, low RBC folate concentrations (-2SD, 875.4 nmol/l) were associated with a 1.8-day delay (95% CI: 1.7-1.8) in development compared with high concentrations (+2SD, 2119.9 nmol/l). tHcy was negatively associated with embryonic development in the total study population (β = -0.08 (95% CI: -0.14; -0.02), P < 0.01), as well as in the IVF/ICSI subgroup (β = -0.08 (95% CI: -0

  20. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    OpenAIRE

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  1. Enrichment of cardiac differentiation of mouse embryonic stem cells by optimizing the hanging drop method.

    Science.gov (United States)

    Chen, Ming; Lin, Yong-Qing; Xie, Shuang-Lun; Wu, Hong-Fu; Wang, Jing-Feng

    2011-04-01

    Hanging drop (HD) culture is used to induce differentiation of embryonic stem cells (ESCs) into other cell types including cardiomyocytes. However, the factors affecting cardiac differentiation of ESCs with this method remain incompletely understood. We have investigated the effects of the starting number of ESCs in embryoid bodies (EBs) and the time of EB adherence to gelatin-coated plates on cardiac differentiation: cardiac differentiation was increased in the EBs by a larger number of ESCs and was decreased by plating EBs at day 4 or earlier. These two factors can thus be optimized to enrich the cardiac differentiation in ESCs using the HD method.

  2. Temperature dependent embryonic development of Trichuris suis eggs in a medicinal raw material

    DEFF Research Database (Denmark)

    Vejzagic, Nermina; Kringel, Helene; Bruun, Johan Musaeus

    2016-01-01

    in Göttingen minipigs.Both male and female pigs were used to evaluate eventual gender specific infectivity. Storage at 30 °C up to 14 weeks and subsequent embryonation for 14 weeks at 25 °C did not significantly reduce the overall larval establishment in minipigs, as compared to storage at 5 °C and subsequent...... analysis (OvaSpec), and an egg hatching assay prior to the final testing in minipigs (Trial 1). These methods showed that the development started earlier at higher temperatures, but the long-term storage at higher temperature affected the egg development. The present study further documents tolerance...

  3. Comparison of Teratoma Formation between Embryonic Stem Cells and Parthenogenetic Embryonic Stem Cells by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Hongyan Tao

    2018-01-01

    Full Text Available With their properties of self-renewal and differentiation, embryonic stem (ES cells hold great promises for regenerative therapy. However, teratoma formation and ethical concerns of ES cells may restrict their potential clinical applications. Currently, parthenogenetic embryonic stem (pES cells have attracted the interest of researchers for its self-renewing and pluripotent differentiation while eliciting less ethic concerns. In this study, we established a model with ES and pES cells both stably transfected with a double-fusion reporter gene containing renilla luciferase (Rluc and red fluorescent protein (RFP to analyze the mechanisms of teratoma formation. Transgenic Vegfr2-luc mouse, which expresses firefly luciferase (Fluc under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2-luc, was used to trace the growth of new blood vessel recruited by transplanted cells. Bioluminescence imaging (BLI of Rluc/Fluc provides an effective tool in estimating the growth and angiogenesis of teratoma in vivo. We found that the tumorigenesis and angiogenesis capacity of ES cells were higher than those of pES cells, in which VEGF/VEGFR2 signal pathway plays an important role. In conclusion, pES cells have the decreased potential of teratoma formation but meanwhile have similar differentiating capacity compared with ES cells. These data demonstrate that pES cells provide an alternative source for ES cells with the risk reduction of teratoma formation and without ethical controversy.

  4. Hediste diversicolor as bioindicator of pharmaceutical pollution: Results from single and combined exposure to carbamazepine and caffeine.

    Science.gov (United States)

    Pires, Adília; Almeida, Ângela; Calisto, Vânia; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

    2016-10-01

    Several environmental stressors have been identified as key and/or emerging drivers of habitat change that could significantly influence marine near-shore ecosystems. These include increasing discharges of pharmaceutical contaminants into the aquatic coastal systems. Pharmaceutical drugs are often detected in aquatic environments but still information on their toxicity impacts on inhabiting species is scarce, especially when acting in combination. Furthermore, almost no information is available on the impacts of pharmaceuticals in polychaetes, often the most abundant taxon in benthic communities and commonly used as indicator species of environmental conditions. Therefore, the present study aimed to evaluate the biochemical alterations induced in the polychaete Hediste diversicolor, from a low contaminated area at the Ria de Aveiro lagoon (Portugal), by the antiepileptic drug carbamazepine (0.0 - control, 0.3, 3.0, 6.0 and 9.0μg/L) and the stimulant caffeine (0.0 - control, 0.5, 3.0, and 18.0μg/L), acting alone and in combination (0.3 CBZ+0.5 CAF and 6.0 CBZ+3.0 CAF). Glutathione S-transferases (GSTs), superoxide dismutase (SOD) and catalase (CAT) activities was determined in Hediste diversicolor from each condition. Lipid peroxidation (LPO), glutathione reduced and oxidized (GSH and GSSG), glycogen and electron transport system (ETS) were also measured. The results obtained clearly revealed that both drugs induced oxidative stress in H. diversicolor, shown by the increase on LPO levels and decrease on total glutathione and GSH/GSSG ratio with the increase of exposure concentrations. Furthermore, the present findings demonstrated that polychaetes biotransformation capacity as well as antioxidant defense mechanisms were not sufficiently efficient to fight against the excess of reactive oxygen species (ROS) leading to LPO when organisms were exposed to both drugs. Our results also demonstrated that polychaetes tended to decrease the activity of ETS when exposed to

  5. Clinical Validation and Implications of Dried Blood Spot Sampling of Carbamazepine, Valproic Acid and Phenytoin in Patients with Epilepsy

    Science.gov (United States)

    Kong, Sing Teang; Lim, Shih-Hui; Lee, Wee Beng; Kumar, Pasikanthi Kishore; Wang, Hwee Yi Stella; Ng, Yan Lam Shannon; Wong, Pei Shieen; Ho, Paul C.

    2014-01-01

    To facilitate therapeutic monitoring of antiepileptic drugs (AEDs) by healthcare professionals for patients with epilepsy (PWE), we applied a GC-MS assay to measure three AEDs: carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) levels concurrently in one dried blood spot (DBS), and validated the DBS-measured levels to their plasma levels. 169 PWE on either mono- or polytherapy of CBZ, PHT or/and VPA were included. One DBS, containing ∼15 µL of blood, was acquired for the simultaneous measurement of the drug levels using GC-MS. Simple Deming regressions were performed to correlate the DBS levels with the plasma levels determined by the conventional immunoturbimetric assay in clinical practice. Statistical analyses of the results were done using MedCalc Version 12.6.1.0 and SPSS 21. DBS concentrations (Cdbs) were well-correlated to the plasma concentrations (Cplasma): r = 0.8381, 0.9305 and 0.8531 for CBZ, PHT and VPA respectively, The conversion formulas from Cdbs to plasma concentrations were [0.89×CdbsCBZ+1.00]µg/mL, [1.11×CdbsPHT−1.00]µg/mL and [0.92×CdbsVPA+12.48]µg/mL respectively. Inclusion of the red blood cells (RBC)/plasma partition ratio (K) and the individual hematocrit levels in the estimation of the theoretical Cplasma from Cdbs of PHT and VPA further improved the identity between the observed and the estimated theoretical Cplasma. Bland-Altman plots indicated that the theoretical and observed Cplasma of PHT and VPA agreed well, and >93.0% of concentrations was within 95% CI (±2SD); and similar agreement (1∶1) was also found between the observed Cdbs and Cplasma of CBZ. As the Cplasma of CBZ, PHT and VPA can be accurately estimated from their Cdbs, DBS can therefore be used for drug monitoring in PWE on any of these AEDs. PMID:25255292

  6. An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

    Science.gov (United States)

    Mishra, Saurabh M; Rohera, Bhagwan D

    2017-11-01

    The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

  7. Transition metal modified and partially calcined inorganic-organic pillared clays for the adsorption of salicylic acid, clofibric acid, carbamazepine, and caffeine from water.

    Science.gov (United States)

    Cabrera-Lafaurie, Wilman A; Román, Félix R; Hernández-Maldonado, Arturo J

    2012-11-15

    Pharmaceutical and Personal Care Products (PPCPs) are considered emerging contaminants, and their efficient removal from water is going to be a challenging endeavor. Microporous adsorbent materials, including pillared clays, could offer a potential solution if tailored properly. Although pillared clays have been employed previously for the removal of organics, the effective removal of PPCPs will only be possible if their surface and textural properties are manipulated from the bottom-up. This work presents the use of modified inorganic-organic pillared clays (IOCs) for the adsorption of salicylic acid, clofibric acid, carbamazepine, and caffeine. The IOCs have been modified with Co(2+), Cu(2+), or Ni(2+) to induce complexation-like adsorbate-adsorbent interactions at ambient conditions, in an attempt to provide an efficient and yet reversible driving force in the sub-ppm concentration range. Furthermore, the IOCs were partially calcined to increase effective surface area by an order of magnitude while preserving some hydrophobicity. In general, the Ni(2+) IOCs exhibited the greatest interaction with salicylic and clofibric acids, respectively, while the Co(2+) adsorbents excelled at adsorbing caffeine at low concentrations. All of the metal-modified IOCs showed comparable adsorption capacities for the case of carbamazepine, probably due to the lack of availability of particular functional groups in this adsorbate. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Nucleosome Organization in Human Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  9. A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs

    CSIR Research Space (South Africa)

    Kwon, Y-J

    2012-03-01

    Full Text Available was screened against seven agonist-induced GPCR internalization cell models as well as transferrin uptake in human embryonic kidney cells. Molecules acting on a single receptor were identified through excluding pan-specific compounds affecting housekeeping...

  10. Embryonic developmental temperatures modulate thermal acclimation of performance curves in tadpoles of the frog Limnodynastes peronii.

    Directory of Open Access Journals (Sweden)

    Frank Seebacher

    Full Text Available Performance curves of physiological rates are not fixed, and determining the extent to which thermal performance curves can change in response to environmental signals is essential to understand the effect of climate variability on populations. The aim of this study was to determine whether and how temperatures experienced during early embryonic development affect thermal performance curves of later life history stages in the frog Limnodynastes peronii. We tested the hypotheses that a the embryonic environment affects mean trait values only; b temperature at which performance of tadpoles is maximal shifts with egg incubation temperatures so that performance is maximised at the incubation temperatures, and c incubation temperatures modulate the capacity for reversible acclimation in tadpoles. Growth rates were greater in warm (25°C compared to cold (15°C acclimated (6 weeks tadpoles regardless of egg developmental temperatures (15°C or 25°C, representing seasonal means. The breadth of the performance curve of burst locomotor performance (measured at 10, 15, 20, 25, and 30°C, representing annual range is greatest when egg developmental and acclimation temperatures coincide. The mode of the performance curves shifted with acclimation conditions and maximum performance was always at higher temperatures than acclimation conditions. Performance curves of glycolytic (lactate dehydrogenase activities and mitochondrial (citrate synthase and cytochrome c oxidase enzymes were modulated by interactions between egg incubation and acclimation temperatures. Lactate dehydrogenase activity paralleled patterns seen in burst locomotor performance, but oxygen consumption rates and mitochondrial enzyme activities did not mirror growth or locomotor performance. We show that embryonic developmental conditions can modulate performance curves of later life-history stages, thereby conferring flexibilty to respond to environmental conditions later in life.

  11. Derivation of novel genetically diverse human embryonic stem cell lines.

    Science.gov (United States)

    Stefanova, Valentina T; Grifo, James A; Hansis, Christoph

    2012-06-10

    Human embryonic stem cells (hESCs) have the potential to revolutionize many biomedical fields ranging from basic research to disease modeling, regenerative medicine, drug discovery, and toxicity testing. A multitude of hESC lines have been derived worldwide since the first 5 lines by Thomson et al. 13 years ago, but many of these are poorly characterized, unavailable, or do not represent desired traits, thus making them unsuitable for application purposes. In order to provide the scientific community with better options, we have derived 12 new hESC lines at New York University from discarded genetically normal and abnormal embryos using the latest techniques. We examined the genetic status of the NYUES lines in detail as well as their molecular and cellular features and DNA fingerprinting profile. Furthermore, we differentiated our hESCs into the tissues most affected by a specific condition or into clinically desired cell types. To our knowledge, a number of characteristics of our hESCs have not been previously reported, for example, mutation for alpha thalassemia X-linked mental retardation syndrome, linkage to conditions with a genetic component such as asthma or poor sperm morphology, and novel combinations of ethnic backgrounds. Importantly, all of our undifferentiated euploid female lines tested to date did not show X chromosome inactivation, believed to result in superior potency. We continue to derive new hESC lines and add them to the NIH registry and other registries. This should facilitate the use of our hESCs and lead to advancements for patient-benefitting applications.

  12. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    Science.gov (United States)

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  13. The 'ventral organs' of Pycnogonida (Arthropoda) are neurogenic niches of late embryonic and post-embryonic nervous system development.

    Science.gov (United States)

    Brenneis, Georg; Scholtz, Gerhard

    2014-01-01

    Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient posterior

  14. The 'ventral organs' of Pycnogonida (Arthropoda are neurogenic niches of late embryonic and post-embryonic nervous system development.

    Directory of Open Access Journals (Sweden)

    Georg Brenneis

    Full Text Available Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i immunolabeling, (ii histology and (iii scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida, the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions - traditionally designated as 'ventral organs' - detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult replenishment of olfactory neurons - as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two

  15. Are there factors preventing cancer development during embryonic life

    International Nuclear Information System (INIS)

    Einhorn, L.

    1983-01-01

    On the basis of the following literature observations, a hypothesis is advanced that the development of cancer is actively inhibited during embryonic life. Although the processes of cell differentiation and proliferation are - without comparison - most pronounced during embryonic life, cancer is rarely found in the newborn and is seldom a cause of neonatal death or spontaneous abortion. Attempts to induce cancer in early-stage animal embryos by irradiation or by transplacental chemical carcinogenesis have been unsuccessful, even when exposed animals have been observed throughout their lifetime. After the period of major organogenesis, however, the embryos become susceptible to carcinogenesis. In humans, the most common embryonic tumors arise in tissues which have an unusually late ongoing development and are still partly immature at or shortly before birth. For many human embryonic tumors the survival rates are higher, and spontaneous regression more frequent, in younger children, i.e. prognosis is age-dependent. Thus, although cancer generally appears in tissues capable of proliferation and differentiation, induction of malignancy in the developmentally most active tissues seems to be beset with difficulty. One possible explanation for this paradox could be that cancer is controlled by the regulators influencing development, regulators that are most active during embryonic life. (Auth.)

  16. Endolymphatic potassium of the chicken vestibule during embryonic development.

    Science.gov (United States)

    Masetto, Sergio; Zucca, Giampiero; Bottà, Luisa; Valli, Paolo

    2005-08-01

    The endolymph fills the lumen of the inner ear membranous labyrinth. Its ionic composition is unique in vertebrates as an extracellular fluid for its high-K(+)/low-Na(+) concentration. The endolymph is actively secreted by specialized cells located in the vestibular and cochlear epithelia. We have investigated the early phases of endolymph secretion by measuring the endolymphatic K(+) concentration in the chicken vestibular system during pre-hatching development. Measurements were done by inserting K(+)-selective microelectrodes in chicken embryo ampullae dissected at different developmental stages from embryonic day 9 up to embryonic day 21 (day of hatching). We found that the K(+) concentration is low (<10mM/L) up to embryonic day 11, afterward it increases steeply to reach a plateau level of about 140 mM/L at embryonic day 19--21. We have developed a short-term in vitro model of endolymph secretion by culturing vestibular ampullae dissected from embryonic day 11 chicken embryos for a few days. The preparation reproduced a double compartment system where the luminal K(+) concentration increased along with the days of culturing. This model could be important for (1) investigating the development of cellular mechanisms contributing to endolymph homeostasis and (2) testing compounds that influence those mechanisms.

  17. Tension (re)builds: Biophysical mechanisms of embryonic wound repair.

    Science.gov (United States)

    Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

    2017-04-01

    Embryonic tissues display an outstanding ability to rapidly repair wounds. Epithelia, in particular, serve as protective layers that line internal organs and form the skin. Thus, maintenance of epithelial integrity is of utmost importance for animal survival, particularly at embryonic stages, when an immune system has not yet fully developed. Rapid embryonic repair of epithelial tissues is conserved across species, and involves the collective migration of the cells around the wound. The migratory cell behaviours associated with wound repair require the generation and transmission of mechanical forces, not only for the cells to move, but also to coordinate their movements. Here, we review the forces involved in embryonic wound repair. We discuss how different force-generating structures are assembled at the molecular level, and the mechanisms that maintain the balance between force-generating structures as wounds close. Finally, we describe the mechanisms that cells use to coordinate the generation of mechanical forces around the wound. Collective cell movements and their misregulation have been associated with defective tissue repair, developmental abnormalities and cancer metastasis. Thus, we propose that understanding the role of mechanical forces during embryonic wound closure will be crucial to develop therapeutic interventions that promote or prevent collective cell movements under pathological conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Induction of murine embryonic stem cell differentiation by medicinal plant extracts

    Energy Technology Data Exchange (ETDEWEB)

    Reynertson, Kurt A. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Charlson, Mary E. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States)

    2011-01-01

    Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells.

  19. Reproductive effects of two neonicotinoid insecticides on mouse sperm function and early embryonic development in vitro.

    Directory of Open Access Journals (Sweden)

    Yi-Hua Gu

    Full Text Available Acetamiprid (ACE and imidacloprid (IMI are two major members in the family of neonicotinoid pesticides, which are synthesized with a higher selectivity to insects. The present study determined and compared in vitro effects of ACE, IMI and nicotine on mammalian reproduction by using an integrated testing strategy for reproductive toxicology, which covered sperm quality, sperm penetration into oocytes and preimplantation embryonic development. Direct chemical exposure (500 µM or 5 mM on spermatozoa during capacitation was performed, and in vitro fertilization (IVF process, zygotes and 2-cell embryos were respectively incubated with chemical-supplemented medium until blastocyst formation to evaluate the reproductive toxicity of these chemicals and monitor the stages mainly affected. Generally, treatment of 500 µM or 5 mM chemicals for 30 min did not change sperm motility and DNA integrity significantly but the fertilization ability in in vitro fertilization (IVF process, indicating that IVF process could detect and distinguish subtle effect of spermatozoa exposed to different chemicals. Culture experiment in the presence of chemicals in medium showed that fertilization process and zygotes are adversely affected by direct exposure of chemicals (PIMI>ACE, whereas developmental progression of 2-cell stage embryos was similar to controls (P>0.05. These findings unveiled the hazardous effects of neonicotinoid pesticides exposure on mammalian sperm fertilization ability as well as embryonic development, raising the concerns that neonicotinoid pesticides may pose reproductive risks on human reproductive health, especially in professional populations.

  20. Induction of murine embryonic stem cell differentiation by medicinal plant extracts.

    Science.gov (United States)

    Reynertson, Kurt A; Charlson, Mary E; Gudas, Lorraine J

    2011-01-01

    Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Pharmaceutical Residues Affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike Wetlands

    DEFF Research Database (Denmark)

    Björklund, Erland; Svahn, Ola; Bak, Søren Alex

    2016-01-01

    This study is the first to investigate the pharmaceutical burden from point sources affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike, Sweden. The investigated Biosphere Reserve is a >1000 km(2) wetland system with inflows from lakes, rivers, leachate from landfill, and wastewater......-treatment plants (WWTPs). We analysed influent and treated wastewater, leachate water, lake, river, and wetland water alongside sediment for six model pharmaceuticals. The two WWTPs investigated released pharmaceutical residues at levels close to those previously observed in Swedish monitoring exercises. Compound......-dependent WWTP removal efficiencies ranging from 12 to 100 % for bendroflumethiazide, oxazepam, atenolol, carbamazepine, and diclofenac were observed. Surface-water concentrations in the most affected lake were ≥100 ng/L for the various pharmaceuticals with atenolol showing the highest levels (>300 ng...

  2. The ethics of patenting human embryonic stem cells.

    Science.gov (United States)

    Chapman, Audrey R

    2009-09-01

    Just as human embryonic stem cell research has generated controversy about the uses of human embryos for research and therapeutic applications, human embryonic stem cell patents raise fundamental ethical issues. The United States Patent and Trademark Office has granted foundational patents, including a composition of matter (or product) patent to the Wisconsin Alumni Research Foundation (WARF), the University of Wisconsin-Madison's intellectual property office. In contrast, the European Patent Office rejected the same WARF patent application for ethical reasons. This article assesses the appropriateness of these patents placing the discussion in the context of the deontological and consequentialist ethical issues related to human embryonic stem cell patenting. It advocates for a patent system that explicitly takes ethical factors into account and explores options for new types of intellectual property arrangements consistent with ethical concerns.

  3. Impact of nutritional stress on early embryonic survival

    Directory of Open Access Journals (Sweden)

    Sukanta Mondal

    2015-09-01

    Full Text Available Background: Low reproductive efficiency is the most critical problem faced by the livestock industry across the globe. Early embryonic loss is one the major cause of poor reproductive efficiency resulting in delayed pregnancy, fewer calves born, reduced milk production, slower genetic progress and substantial financial loss to the beef or dairy industry. The establishment of pregnancy results from the interaction between the embryo and the dam and is the culmination of a series of events initiated with development of the follicle and gametes. Among numerous internal and external factors nutrition has the potency to alter the micro-environment of the oocyte and the embryo, making it more hostile to optimal fertilization and pre-implantation embryonic growth. Understanding the impact of nutritional stress on oocyte function, embryo development and reciprocal signaling networks between the embryo and uterus will lead to alleviation of the problems of early embryonic mortality.

  4. Ultrasonographic appearance of early embryonic mortality in buffalo (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Giuseppe Catone

    2010-01-01

    Full Text Available Embryonic mortality is one of the main causes responsible of the decline in fertility that occurs in buffaloes during periods of increasing daylight length (out sexual breeding season. Transrectal ultrasonography for pregnancy diagnosis offers some advantages over palpation per rectum: earlier diagnosis of pregnancy/non-pregnancy, determination of embryo/fetus viability, reduction of misdiagnosis, and reduction of .potential. iatrogenic embryo/fetal attrition. Non pregnant buffaloes on Day 25 after AI showed higher Resistive Index (RI (P<0.05 and Pulsatility Index (P=0.07 values, registered on CL on Days 10 after AI, compared to pregnant buffaloes. RI values were significantly higher (P=0.02 in non pregnant buffaloes also on Day 45 after AI. Colour Doppler sonography could be used to gain specific information relating to the ovarian blood flow in predicting early embryonic loss and to describe the ultrasonographic features of early embryonic death in buffaloes.

  5. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  6. PTBP1 is required for embryonic development before gastrulation.

    Science.gov (United States)

    Suckale, Jakob; Wendling, Olivia; Masjkur, Jimmy; Jäger, Melanie; Münster, Carla; Anastassiadis, Konstantinos; Stewart, A Francis; Solimena, Michele

    2011-02-17

    Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures.

  7. High doses of carbamazepine for refractory partial epilepsy Altas doses de carbamazepina para epilepsia parcial refratária

    Directory of Open Access Journals (Sweden)

    Cristiana Borges Pereira

    1996-03-01

    Full Text Available Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ. Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1. Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6. Seizure's control was observed in 7 (14.48% patients taking 1200 mg/day and in 2 (4.16% patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%. Ten patients (20.81% had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.Foram analisados 48 pacientes epilépticos com crises parciais que faziam uso de carbamazepina (CBZ em doses iguais ou superiores a 1200 mg por dia. Trinta e três estavam em monoterapia e 15 em politerapia. As outras medicações foram mantidas constantes durante a manipulação da dose de CBZ nos pacientes em politerapia. O critério utilizado para o aumento da dose de CBZ foi a falta de controle clínico e a ausência de efeitos colaterais (independente da dosagem sérica. A dose máxima variou de 1200 a 1900 mg/dia (1200 mg, n=18; 1300 mg/dia, n=1; 1400 mg/dia, n=7; 1600 mg/dia, n=9; 1700 mg/dia, n=4; 1800 mg/dia, n=8 ; 1900 mg/dia, n=1. Dosagens séricas de anticonvulsivantes eram utilizadas no sentido de confirmar a aderência ao tratamento. A média das dosagens disponíveis foi de 9,6 ug/mL. O tempo de seguimento variou de 3 a 96 meses (M=25

  8. Cell surface carbohydrate changes during embryonic and fetal skin development

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Holbrook, K; Clausen, H

    1986-01-01

    Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N-acetyllac......Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N...

  9. Differentiation of Mouse Embryonic Stem Cells into Ventral Foregut Precursors

    DEFF Research Database (Denmark)

    Rothová, Michaela; Hölzenspies, Jurriaan J; Livigni, Alessandra

    2016-01-01

    Anterior definitive endoderm (ADE), the ventral foregut precursor, is both an important embryonic signaling center and a unique multipotent precursor of liver, pancreas, and other organs. Here, a method is described for the differentiation of mouse embryonic stem cells (mESCs) to definitive...... endoderm with pronounced anterior character. ADE-containing cultures can be produced in vitro by suspension (embryoid body) culture or in a serum-free adherent monolayer culture. ESC-derived ADE cells are committed to endodermal fates and can undergo further differentiation in vitro towards ventral foregut...

  10. Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 Caenorhabditis elegans.

    Science.gov (United States)

    Katner, Simon N; Neal-Beliveau, Bethany S; Engleman, Eric A

    2016-01-01

    Methamphetamine (MAP) addiction is substantially prevalent in today's society, resulting in thousands of deaths and costing billions of dollars annually. Despite the potential deleterious consequences, few studies have examined the long-term effects of embryonic MAP exposure. Using the invertebrate nematode Caenorhabditis elegans allows for a controlled analysis of behavioral and neurochemical changes due to early developmental drug exposure. The objective of the current study was to determine the long-term behavioral and neurochemical effects of embryonic exposure to MAP in C. elegans. In addition, we sought to improve our conditioning and testing procedures by utilizing liquid filtration, as opposed to agar, and smaller, 6-well testing plates to increase throughput. Wild-type N2 C. elegans were embryonically exposed to 50 μM MAP. Using classical conditioning, adult-stage C. elegans were conditioned to MAP (17 and 500 μM) in the presence of either sodium ions (Na+) or chloride ions (Cl-) as conditioned stimuli (CS+/CS-). Following conditioning, a preference test was performed by placing worms in 6-well test plates spotted with the CS+ and CS- at opposite ends of each well. A preference index was determined by counting the number of worms in the CS+ target zone divided by the total number of worms in the CS+ and CS- target zones. A food conditioning experiment was also performed in order to determine whether embryonic MAP exposure affected food conditioning behavior. For the neurochemical experiments, adult worms that were embryonically exposed to MAP were analyzed for dopamine (DA) content using high-performance liquid chromatography. The liquid filtration conditioning procedure employed here in combination with the use of 6-well test plates significantly decreased the time required to perform these experiments and ultimately increased throughput. The MAP conditioning data found that pairing an ion with MAP at 17 or 500 μM significantly increased the preference

  11. Influence of demineralized bone matrix's embryonic origin on bone formation: an experimental study in rats.

    Science.gov (United States)

    Stavropoulos, Andreas; Kostopoulos, Lambros; Mardas, Nicolaos; Karring, Thorkild

    2003-01-01

    There are results suggesting that differences regarding bone-inducing potential, in terms of amount and/or rate of bone formation, exist between demineralized bone matrices (DBMs) of different embryonic origins. The aim of the present study was to examine whether the embryonic origin of DBM affects bone formation when used as an adjunct to guided tissue regeneration (GTR). Endomembranous (EM) and endochondral (ECH) DBMs were produced from calvarial and long bones of rats, respectively. Prior to the study the osteoinductive properties of the DBMs were confirmed in six rats following intramuscular implantation. Following surgical exposure of the mandibular ramus, a rigid hemispheric Teflon capsule loosely packed with a standardized quantity of DBM was placed with its open part facing the lateral surface of the ramus in both sides of the jaw in 30 rats. In one side of the jaw, chosen at random, the capsule was filled with EM-DBM, whereas in the other side ECH-DBM was used. Groups of 10 animals were sacrificed after healing periods of 1, 2, and 4 months, and undecalcified sections of the capsules were produced and subjected to histologic analysis and computer-assisted planimetric measurements. During the experiment increasing amounts of newly formed bone were observed inside the capsules in both sides of the animals' jaws. Limited bone formation was observed in the 1- and 2-month specimens, but after 4 months of healing, the newly formed bone in the ECH-DBM grafted sides occupied 59.1% (range 45.6-74.7%) of the area created by the capsule versus 46.9% (range 23.0-64.0%) in the EM-DBM grafted sides (p =.01). It is concluded that the embryonic origin of DBM influences bone formation by GTR and that ECH-DBM is superior to EM-DBM.

  12. Effect of cadmium, lead and arsenic on the oviposition, hatching and embryonic survival of Biomphalaria glabrata

    International Nuclear Information System (INIS)

    Ansaldo, Martin; Nahabedian, Daniel E.; Di Fonzo, Carla; Wider, Eva A.

    2009-01-01

    Biomphalaria glabrata is a widespread freshwater gastropod mollusc. The easy aquaculture of these organisms allow its use as an accessible tool for contamination bioassays. B. glabrata showed marked metabolic responses when exposed to cadmium, lead and arsenic. Those responses could also affect the reproduction of the snails. Taking into account this hypothesis, B. glabrata were exposed for 96 h (acute laboratory bioassays) to different concentrations of cadmium (0.1, 0.05 and 0 mg/L), lead (0.5, 0.1, 0.05 and 0 mg/L) and arsenic (0.5, 0.1, 0.05 and 0 mg/L). Snails were removed from the aquaria while eggs were left in the same contaminant concentrations. The effect of the assayed toxicants on snail reproduction was registered as the alterations of the total number of laid eggs (TNLE), hatching time and embryonic survival. At 0.10 mg/L cadmium significantly decreased the TNLE (p < 0.05) and no embryos survived. The lowest assayed level (0.05 mg/L) of cadmium, delayed the hatching time twice when it was compared with the control group (p < 0.01). Lead decreased the TNLE at 0.5 mg/L level (p < 0.01). The other assayed doses (0.05 and 0.10 mg/L) also decreased embryonic survival significantly (p < 0.05 and p < 0.01 respectively) and extended twice the time to hatching (p < 0.01). The 0.50 mg/L level killed all embryos. Arsenic at all studied concentrations decreased the TNLE (p < 0.05) while the hatching time was increased by 50%. Embryo survival only decreased at the highest level (0.5 mg/L) of arsenic assayed. In summary, the acute exposure (96 h) to cadmium lead and arsenic, altered the reproduction of B. glabrata, modifying the TNLE, hatching time and embryonic survival

  13. Simultaneous Detection of Sulfamethoxazole, Diclofenac, Carbamazepine, and Bezafibrate by Solid Phase Extraction and High Performance Liquid Chromatography with Diode Array Detection

    Science.gov (United States)

    Zhou, Z.; Jiang, J.-Q.

    2014-05-01

    A method of solid phase extraction (SPE) coupled with high performance liquid chromatography and diode array detection (HPLC-DAD) was studied for the simultaneous determination of sulfamethoxazole (SMX), diclofenac (DCF), carbamazepine (CBZ), and bezafi brate (BZF) in test solutions. The target compounds were extracted by SPE from samples, and the resulting elutes were analyzed using a HPLC-DAD system at wavelengths of 270, 280, 290, and 230 nm for SMX, DCF, CBZ, and BZF, respectively. This method shows good recoveries for SMX, DCF, CBZ, and BZF with mean recoveries of 89.7 ± 9.3%, 86.1 ± 7.6%, 95.0 ± 6.5%, and 94.0 ± 5.4%, respectively.

  14. Photo-transfection of mouse embryonic stem cells with plasmid DNA using femtosecond laser pulses

    CSIR Research Space (South Africa)

    Thobakgale, Lebogang

    2017-01-01

    Full Text Available This presentation is about the photo-transfection of mouse embryonic stem cells with plasmid DNA using femtosecond laser pulses. It outlines the background on embryonic stem cells (ES) and phototransfection....

  15. Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells

    DEFF Research Database (Denmark)

    Galli, Giorgio Giacomo; Carrara, Matteo; Francavilla, Chiara

    2013-01-01

    PRDM proteins belong to the SET- domain protein family involved in the regulation of gene expression. Although few PRDM members possess histone methyltransferase activity, the molecular mechanisms by which the other members exert transcriptional regulation remain to be delineated. In this study, we...... find that Prdm5 is highly expressed in mouse embryonic stem cells (mES) and exploit this cellular system to characterize molecular functions of Prdm5. By combining proteomics and next generation sequencing technologies we identify Prdm5 interaction partners and genomic occupancy. We demonstrate that......, despite Prdm5 is dispensable for mES cell maintenance, it directly targets genomic regions involved in early embryonic development and affects the expression of a subset of developmental regulators during cell differentiation. Importantly, Prdm5 interacts with Ctcf, Cohesin and TFIIIC and co...

  16. Dissipation of triclosan, triclocarban, carbamazepine and naproxen in agricultural soil following surface or sub-surface application of dewatered municipal biosolids

    International Nuclear Information System (INIS)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Lapen, David R.; Topp, Edward

    2015-01-01

    In many jurisdictions land application of municipal biosolids is a valued source of nutrients for crop production. The practice must be managed to ensure that crops and adjacent water are not subject to contamination by pharmaceuticals or other organic contaminants. The broad spectrum antimicrobial agents triclosan (TCS) and triclocarban (TCC), the anti-epileptic drug carbamazepine (CBZ), and the nonsteroidal anti-inflammatory drug naproxen (NAP) are widely used and are carried in biosolids. In the present study, the effect of biosolids and depth of placement in the soil profile on the rates of TCS, TCC, CBZ, and NAP dissipation were evaluated under semi-field conditions. Aggregates of dewatered municipal biosolids (DMBs) supplemented with 14 C-labeled residues were applied either on the soil surface or in the subsurface of the soil profile, and incubated over several months under ambient outdoor conditions. The dissipation of TCS, TCC and NAP was significantly faster in sub-surface than surface applied biosolid aggregates. In contrast the dissipation rate for CBZ was the same in surface applied and incorporated aggregates. Overall, the present study has determined a significant effect of depth of placement on the dissipation rate of biodegradable molecules. - Highlights: • We characterized the soil fate of four organic contaminants carried in biosolids. • Biosolids were placed on the soil surface or incorporated within the soil profile. • Naproxen, triclosan and triclocarban were dissipated more rapidly when incorporated. • Depth of placement did not influence the rate of carbamazepine dissipation. • Soil incorporation of biosolids will result in more rapid dissipation of contaminants

  17. Therapeutic drug monitoring of carbamazepine and its metabolite in children from dried blood spots using liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Shokry, Engy; Villanelli, Fabio; Malvagia, Sabrina; Rosati, Anna; Forni, Giulia; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria; Guerrini, Renzo; la Marca, Giancarlo

    2015-05-10

    Carbamazepine (CBZ) is a first-line drug for the treatment of different forms of epilepsy and the first choice drug for trigeminal neuralgia. CBZ is metabolized in the liver by oxidation into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent and known to contribute to the pharmacological activity of CBZ. The aim of the present study was to develop and validate a reliable, selective and sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of CBZ and its active metabolite in dried blood spots (DBS). The extraction process was carried out from DBS using methanol-water-formic acid (80:20:0.1, v/v/v). Chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50mL/min. The method was linear over the range 1-40mg/L and 0.25-20mg/L for CBZ and CBZE, respectively. The limit of quantification was 0.75mg/L and 0.25mg/L for CBZ and CBZE. Intra-day and inter-day assay precisions were found to be lower than 5.13%, 6.46% and 11.76%, 4.72% with mean percentage accuracies of 102.1%, 97.5% and 99.2%, 97.8% for CBZ and CBZE. We successfully applied the method for determining DBS finger-prick samples in paediatric patients and confirmed the results with concentrations measured in matched plasma samples. This novel approach allows quantification of CBZ and its metabolite from only one 3.2mm DBS disc by LC-MS/MS thus combining advantages of DBS technique and LC-MS/MS in clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Dissipation of triclosan, triclocarban, carbamazepine and naproxen in agricultural soil following surface or sub-surface application of dewatered municipal biosolids

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne [Agriculture and Agri-Food Canada, London, ON N5V 4T3 (Canada); Lapen, David R. [Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6 (Canada); Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON N5V 4T3 (Canada); Department of Biology, Western University, London, ON N6A 5B7 (Canada)

    2015-04-15

    In many jurisdictions land application of municipal biosolids is a valued source of nutrients for crop production. The practice must be managed to ensure that crops and adjacent water are not subject to contamination by pharmaceuticals or other organic contaminants. The broad spectrum antimicrobial agents triclosan (TCS) and triclocarban (TCC), the anti-epileptic drug carbamazepine (CBZ), and the nonsteroidal anti-inflammatory drug naproxen (NAP) are widely used and are carried in biosolids. In the present study, the effect of biosolids and depth of placement in the soil profile on the rates of TCS, TCC, CBZ, and NAP dissipation were evaluated under semi-field conditions. Aggregates of dewatered municipal biosolids (DMBs) supplemented with {sup 14}C-labeled residues were applied either on the soil surface or in the subsurface of the soil profile, and incubated over several months under ambient outdoor conditions. The dissipation of TCS, TCC and NAP was significantly faster in sub-surface than surface applied biosolid aggregates. In contrast the dissipation rate for CBZ was the same in surface applied and incorporated aggregates. Overall, the present study has determined a significant effect of depth of placement on the dissipation rate of biodegradable molecules. - Highlights: • We characterized the soil fate of four organic contaminants carried in biosolids. • Biosolids were placed on the soil surface or incorporated within the soil profile. • Naproxen, triclosan and triclocarban were dissipated more rapidly when incorporated. • Depth of placement did not influence the rate of carbamazepine dissipation. • Soil incorporation of biosolids will result in more rapid dissipation of contaminants.

  19. Adsorption Capacity of a Volcanic Rock—Used in ConstructedWetlands—For Carbamazepine Removal, and Its Modification with Biofilm Growth

    Directory of Open Access Journals (Sweden)

    Allan Tejeda

    2017-09-01

    Full Text Available In this study, the aim was to evaluate the adsorption capacity of a volcanic rock commonly used in Mexico as filter medium in constructed wetlands (locally named tezontle for carbamazepine (CBZ adsorption, as well as to analyze the change in its capacity with biofilm growth. Adsorption essays were carried out under batch conditions by evaluating two particle sizes of tezontle, two values of the solution pH, and two temperatures; from these essays, optimal conditions for carbamazepine adsorption were obtained. The optimal conditions (pH 8, 25 °C and 0.85–2.0 mm particle-size were used to evaluate the adsorption capacity of tezontle with biofilm, which was promoted through tezontle exposition to wastewater in glass columns, for six months. The maximum adsorption capacity of clean tezontle was 3.48 µg/g; while for the tezontle with biofilm, the minimum value was 1.75 µg/g (after the second week and the maximum, was 3.3 µg/g (after six months with a clear tendency of increasing over time. The adsorption kinetic was fitted to a pseudo-second model for both tezontle without biofilm and with biofilm, thus indicating a chemisorption process. On clean tezontle, both acid active sites (AAS and basic active sites (BAS were found in 0.087 and 0.147 meq/g, respectively. The increase in the adsorption capacity of tezontle with biofilm, along the time was correlated with a higher concentration of BAS, presumably from a greater development of biofilm. The presence of biofilm onto tezontle surface was confirmed through FTIR and FE-SEM. These results confirm the essential role of filter media for pharmaceutical removal in constructed wetlands (CWs.

  20. Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions

    DEFF Research Database (Denmark)

    Morgani, Sophie M; Canham, Maurice A; Nichols, Jennifer

    2013-01-01

    Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought...... not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants....

  1. Ovarian activity and early embryonic development in the rusty bat ...

    African Journals Online (AJOL)

    The reproductive pattern of the female rusty bat, Pipistrellus rusticus, was investigated by means of a histological examination of the ovarian follicles as well as early embryonic development. Bats were collected from two localities in Limpopo Province. Female rusty bats are seasonal monestrous breeders, initiating ...

  2. Early Embryonic Heart Rate in Normal Pregnancies In Memory of ...

    African Journals Online (AJOL)

    To determine the appearance and development of embryonic heart rate a total of n = 317 Nigerian pregnant women were studied in the very early pregnancy from 23 – 56 days from the onset of last menstrual period (LMP). All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was ...

  3. optimization of protocol for m apical meristem of embryonic axes

    African Journals Online (AJOL)

    userpc

    The hypocotyl segments, prima were removed and embryonic axes were placed in culture bott nd Skoog basal + B5 vitamins (MSB5) fortified with 22.2µM, 26.6µM opurine (BAP) to induce multiple shoots. Elongated shoots we tion media consisting of MSB5 supplemented with low concentrati one free media promoted direct ...

  4. Phosphorylation dynamics during early differentiation of human embryonic stem cells

    NARCIS (Netherlands)

    van Hoof, D.; Munoz, J.; Braam, S.R.; Pinkse, M.W.H.; Linding, R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2009-01-01

    Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during

  5. Improved genetic manipulation of human embryonic stem cells.

    NARCIS (Netherlands)

    Braam, S.R.; Denning, C.; van den Brink, S.; Kats, P.; Hochstenbach, R.; Passier, R.; Mummery, C.L.

    2008-01-01

    Low efficiency of transfection limits the ability to genetically manipulate human embryonic stem cells (hESCs), and differences in cell derivation and culture methods require optimization of transfection protocols. We transiently transferred multiple independent hESC lines with different growth

  6. Twenty years of embryonic stem cell research in farm animals

    Science.gov (United States)

    Notable distinctions between an embryonic stem cell (ESC) and somatic cell are that the ESC can maintain an undifferentiated state indefinitely, self renew, and is pluripotent, meaning that the ESC can potentially generate cells representing all the three primordial germ layers and contribute to the...

  7. Meeting embryonic requirements of broilers throughout incubation: a review

    Directory of Open Access Journals (Sweden)

    R Molenaar

    2010-09-01

    Full Text Available During incubation of chicken embryos, environmental conditions, such as temperature, relative humidity, and CO2 concentration, must be controlled to meet embryonic requirements that change during the different phases of embryonic development. In the current review, the effects of embryo temperature, egg weight loss, and CO2 concentration on hatchability, hatchling quality, and subsequent performance are discussed from an embryonic point of view. In addition, new insights related to the incubation process are described. Several studies have shown that a constant eggshell temperature (EST of 37.5 to 38.0°C throughout incubation results in the highest hatchability, hatchling quality, and subsequent performance. Egg weight loss must be between 6.5 and 14.0% of the initial egg weight, to obtain an adequate air cell size before the embryo internally pips. An increased CO2 concentration during the developmental phase of incubation (first 10 days can accelerate embryonic development and hatchability, but the physiological mechanisms of this acceleration are not completely understood. Effects of ar increased CO2 concentration during late incubation also need further investigation. The preincubation warming profile, thermal manipulation, and in ovo feeding are new insights related to the incubation process and show that the optimal situation for the embryo during incubation highly depends on the conditions of the eggs before (storage duration and during incubation (environmental conditions and on the conditions of the chickens after hatching (environmental temperature.

  8. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Chicken embryonic stem (ES) cells are useful for producing transgenic chickens and preserving genetic material in avian species. In this study, the differentiation potential of chicken ES cells was investigated in vitro. Chicken ES cells were differentiated into osteoblasts cultured for 15 to 21 days in the induction media ...

  9. Impact of 2-bromopropane on mouse embryonic stem cells and ...

    African Journals Online (AJOL)

    This study shows that 2-BP (5 to 10 μM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no effects at treatment dosages below 5 μM. In ESC-B5 cells, 2-BP directly increased the content of reactive oxygen species (ROS), significantly increased the cytoplasmic free calcium and nitric oxide ...

  10. In vitro differentiation of mouse embryonic stem cells into functional ...

    African Journals Online (AJOL)

    Studies have shown that embryonic stem (ES) cells can be successfully differentiated into liver cells, which offer the potential unlimited cell source for a variety of end-stage liver disease. In our study, in order to induce mouse ES cells to differentiate into hepatocyte-like cells under chemically defined conditions, ES cells ...

  11. Derivation of the human embryonic stem cell line RCM1

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-03-01

    Full Text Available The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

  12. Ultrastructure, development, and homology of insect embryonic cuticles

    Czech Academy of Sciences Publication Activity Database

    Konopová, Barbora; Zrzavý, Jan

    2005-01-01

    Roč. 264, č. 3 (2005), s. 339-362 ISSN 0362-2525 R&D Projects: GA ČR(CZ) GD206/03/H034 Institutional research plan: CEZ:AV0Z50070508 Keywords : embryonic development * cuticle * metamorphosis Subject RIV: EA - Cell Biology Impact factor: 1.421, year: 2005

  13. On the phylogeny of the embryonic apparatus of some Foraminifera

    NARCIS (Netherlands)

    Cosijn, A.J.

    1942-01-01

    In the following pages data will be given about the size of the megalospheric embryonic apparatus, and of the size of the shell, of some Foraminifera. By comparing these data for a certain species from different samples, the relative ages of which are known, it will be possible, to get an insight

  14. Effects of Exogenous Oxytocin on Embryonic Survival in Cows

    Directory of Open Access Journals (Sweden)

    A. Yildiz

    2006-01-01

    Full Text Available The aim of this study was to evaluate the effect of oxytocin on embryonic survival in dairy cows. Pregnancy was verified using the early pregnancy factor (EPF activity on Day 4 after artificial insemination (AI. Pregnant cows were randomly allotted to two groups: treated (n = 8 and control (n = 8. Oxytocin (100 IU, 5 ml, DIF Turkey was administered twice daily by intravenous injections to treated cows and sterile saline (5 ml to control cows immediately before milking on days 4 to 7 after AI. Blood samples were taken via jugular vein every day from day 4 to 8 and every other day until Day 20 following insemination to evaluate the effect of oxytocin on embryonic survival. The embryonic loss was diagnosed in 3 of the 8 cows treated with oxytocin, and embryonic survival rate was 62.5% in this group versus 87.5% in controls. Short cycles occurred in 37.5% of oxytocin-treated cows. At the same time their serum progesterone concentrations rose more slowly than in controls. It was concluded that cows administered oxytocin on days 4 to 7 after insemination are at a higher risk of pregnancy loss.

  15. Innovative virtual reality measurements for embryonic growth and development

    NARCIS (Netherlands)

    C.M. Verwoerd-Dikkeboom (Christine); A.H.J. Koning (Anton); W.C.J. Hop (Wim); P.J. van der Spek (Peter); N. Exalto (Niek); R.P.M. Steegers-Theunissen (Régine)

    2010-01-01

    textabstractBackground Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. Methods In a longitudinal study, three-dimensional

  16. Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Anuradha; Krishna, Amitabh

    2014-12-01

    The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

  17. File list: ALL.Emb.20.AllAg.Embryonic_testis [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.Embryonic_palates mm9 Input control Embryo Embryonic palates http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.Embryonic_palates.bed ...

  6. File list: NoD.Emb.50.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.50.AllAg.Embryonic_palates mm9 No description Embryo Embryonic palates ERX6...50310 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.50.AllAg.Embryonic_palates.bed ...

  7. File list: NoD.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.05.AllAg.Embryonic_palates mm9 No description Embryo Embryonic palates ERX6...50310 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.05.AllAg.Embryonic_palates.bed ...

  8. File list: ALL.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.05.AllAg.Embryonic_palates mm9 All antigens Embryo Embryonic palates ERX650...310 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.05.AllAg.Embryonic_palates.bed ...

  9. File list: InP.Emb.50.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_palates mm9 Input control Embryo Embryonic palates http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_palates.bed ...

  10. File list: ALL.Emb.20.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.Embryonic_palates mm9 All antigens Embryo Embryonic palates ERX650...310 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.Embryonic_palates.bed ...

  11. File list: ALL.Emb.50.AllAg.Embryonic_palates [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.Embryonic_palates mm9 All antigens Embryo Embryonic palates ERX650...310 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.Embryonic_palates.bed ...

  12. File list: Pol.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.50.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.50.AllAg.Embryonic_heart.bed ...

  13. File list: ALL.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.10.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX1437350...RX1437340,SRX1437357,SRX1437344,SRX1437336,SRX1437356,SRX377685,SRX022494,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.10.AllAg.Embryonic_heart.bed ...

  14. File list: InP.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX967652...RX967654,SRX377683,SRX185886,SRX698167,SRX244285,SRX377687,SRX377685 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.Embryonic_heart.bed ...

  15. File list: His.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.20.AllAg.embryonic_skin mm9 Histone Embryo embryonic skin SRX1062969,SRX106...2968,SRX1062966,SRX1062965 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.20.AllAg.embryonic_skin.bed ...

  16. File list: ALL.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.embryonic_skin mm9 All antigens Embryo embryonic skin SRX1062969,S...RX1062968,SRX1062966,SRX1062967,SRX1062972,SRX1062971,SRX1062970,SRX1062965 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.embryonic_skin.bed ...

  17. File list: His.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.50.AllAg.embryonic_skin mm9 Histone Embryo embryonic skin SRX1062969,SRX106...2968,SRX1062966,SRX1062965 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.50.AllAg.embryonic_skin.bed ...

  18. File list: His.Emb.05.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.05.AllAg.embryonic_skin mm9 Histone Embryo embryonic skin SRX1062965,SRX106...2966,SRX1062968,SRX1062969 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.05.AllAg.embryonic_skin.bed ...

  19. File list: InP.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.embryonic_skin mm9 Input control Embryo embryonic skin SRX1062967,...SRX1062972 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.embryonic_skin.bed ...

  20. File list: InP.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.embryonic_skin mm9 Input control Embryo embryonic skin SRX1062972,...SRX1062967 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.embryonic_skin.bed ...

  1. File list: ALL.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.embryonic_skin mm9 All antigens Embryo embryonic skin SRX1062969,S...RX1062968,SRX1062966,SRX1062971,SRX1062967,SRX1062972,SRX1062965,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.embryonic_skin.bed ...

  2. File list: Oth.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.50.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.50.AllAg.embryonic_skin.bed ...

  3. File list: ALL.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.10.AllAg.embryonic_skin mm9 All antigens Embryo embryonic skin SRX1062972,S...RX1062971,SRX1062966,SRX1062969,SRX1062968,SRX1062965,SRX1062967,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.10.AllAg.embryonic_skin.bed ...

  4. File list: Oth.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.20.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.20.AllAg.embryonic_skin.bed ...

  5. File list: Oth.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.10.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.10.AllAg.embryonic_skin.bed ...

  6. File list: Oth.Emb.05.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.embryonic_skin mm9 TFs and others Embryo embryonic skin SRX1062971...,SRX1062970 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.embryonic_skin.bed ...

  7. File list: InP.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.embryonic_skin mm9 Input control Embryo embryonic skin SRX1062967,...SRX1062972 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.embryonic_skin.bed ...

  8. File list: InP.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX143735...RX377685,SRX377687,SRX967654,SRX077933,SRX377683,SRX967652,SRX244285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_heart.bed ...

  9. File list: ALL.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX112938,...7,SRX967654,SRX967653,SRX1100404,SRX244285,SRX112936,SRX1100405,SRX022494,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.Embryonic_heart.bed ...

  10. File list: Pol.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.20.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.AllAg.Embryonic_heart.bed ...

  11. File list: Unc.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.20.AllAg.Embryonic_heart mm9 Unclassified Embryo Embryonic heart SRX248279,...SRX190172,SRX112936,SRX022494 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.20.AllAg.Embryonic_heart.bed ...

  12. File list: NoD.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.10.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...02,SRX1100404,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.10.AllAg.Embryonic_heart.bed ...

  13. File list: ALL.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.05.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX967652,...4,SRX1437348,SRX377683,SRX377685,SRX377687,SRX190172,SRX244285,SRX1100405,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.05.AllAg.Embryonic_heart.bed ...

  14. File list: InP.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX967652...RX077933,SRX377683,SRX377685,SRX377681,SRX377687,SRX967654,SRX244285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.Embryonic_heart.bed ...

  15. File list: ALL.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.Embryonic_heart mm9 All antigens Embryo Embryonic heart SRX112938,...52,SRX967653,SRX112936,SRX1100405,SRX112937,SRX185857,SRX244285,SRX022494,SRX337963 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.Embryonic_heart.bed ...

  16. File list: Pol.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.10.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.10.AllAg.Embryonic_heart.bed ...

  17. File list: Pol.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Emb.05.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.AllAg.Embryonic_heart.bed ...

  18. File list: Unc.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Emb.50.AllAg.Embryonic_heart mm9 Unclassified Embryo Embryonic heart SRX248279,...SRX190172,SRX112936,SRX022494 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.50.AllAg.Embryonic_heart.bed ...

  19. File list: InP.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.05.AllAg.Embryonic_heart mm9 Input control Embryo Embryonic heart SRX967652...RX698167,SRX377681,SRX967654,SRX377683,SRX377685,SRX377687,SRX244285 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.05.AllAg.Embryonic_heart.bed ...

  20. File list: NoD.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.20.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...02,SRX1100404,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.20.AllAg.Embryonic_heart.bed ...

  1. File list: NoD.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.05.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...04,SRX1100402,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.05.AllAg.Embryonic_heart.bed ...

  2. File list: NoD.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.50.AllAg.Embryonic_heart mm9 No description Embryo Embryonic heart SRX11004...02,SRX1100404,SRX1100405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.50.AllAg.Embryonic_heart.bed ...

  3. Childhood Central Nervous System Embryonal Tumors (PDQ®)—Health Professional Version

    Science.gov (United States)

    Pediatric CNS embryonal tumors are a collection of heterogeneous lesions (medulloblastoma, and nonmedulloblastoma). Molecular genetic studies are used to classify embryonal tumors, stratify risk, and plan treatment. Get detailed information about tumor biology, diagnosis, prognosis, and treatment of untreated and recurrent CNS embryonal tumors in this summary for clinicians.

  4. File list: His.Emb.10.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.10.AllAg.Embryonic_trunk mm9 Histone Embryo Embryonic trunk SRX093317,SRX09...3316 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.10.AllAg.Embryonic_trunk.bed ...

  5. File list: DNS.Emb.10.AllAg.Embryonic_limb [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.10.AllAg.Embryonic_limb mm9 DNase-seq Embryo Embryonic limb SRX191032,SRX19...1037 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.10.AllAg.Embryonic_limb.bed ...

  6. File list: InP.Emb.50.AllAg.Embryonic_eye [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_eye mm9 Input control Embryo Embryonic eye SRX804057,SRX...804055 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_eye.bed ...

  7. File list: InP.Emb.50.AllAg.Embryonic_limb [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_limb mm9 Input control Embryo Embryonic limb SRX804047,S...69,SRX083262,SRX083272 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_limb.bed ...

  8. File list: InP.Emb.50.AllAg.Embryonic_flank [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_flank mm9 Input control Embryo Embryonic flank SRX804059... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_flank.bed ...

  9. File list: NoD.Emb.20.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.20.AllAg.Embryonic_trunk mm9 No description Embryo Embryonic trunk ERX40226...7,ERX402264 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.20.AllAg.Embryonic_trunk.bed ...

  10. File list: Oth.Emb.05.AllAg.Embryonic_face [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.Embryonic_face mm9 TFs and others Embryo Embryonic face SRX330164,...SRX139877 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Embryonic_face.bed ...

  11. File list: DNS.Emb.20.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.20.AllAg.Embryonic_trunk mm9 DNase-seq Embryo Embryonic trunk SRX191030 htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.20.AllAg.Embryonic_trunk.bed ...

  12. File list: His.Emb.50.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.50.AllAg.Embryonic_trunk mm9 Histone Embryo Embryonic trunk SRX093317,SRX09...3316 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.50.AllAg.Embryonic_trunk.bed ...

  13. Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification

    NARCIS (Netherlands)

    Dartel, van D.A.M.; Schulpen, S.H.; Theunissen, P.T.; Bunschoten, A.; Piersma, A.H.; Keijer, J.

    2014-01-01

    Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in

  14. File list: ALL.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.20.AllAg.Embryonic_pancreas mm9 All antigens Embryo Embryonic pancreas SRX2...87023,SRX287022,SRX287021,SRX287020,SRX287016,SRX287026,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.20.AllAg.Embryonic_pancreas.bed ...

  15. File list: Oth.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.05.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287017,SRX287023,SRX287022,SRX287021,SRX287020,SRX287016 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Embryonic_pancreas.bed ...

  16. File list: ALL.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Emb.50.AllAg.Embryonic_pancreas mm9 All antigens Embryo Embryonic pancreas SRX2...87021,SRX287020,SRX287023,SRX287016,SRX287022,SRX287026,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Emb.50.AllAg.Embryonic_pancreas.bed ...

  17. File list: Oth.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.50.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287021,SRX287020,SRX287023,SRX287016,SRX287022,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.50.AllAg.Embryonic_pancreas.bed ...

  18. File list: InP.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.05.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.05.AllAg.Embryonic_pancreas.bed ...

  19. File list: InP.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_pancreas.bed ...

  20. File list: NoD.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.10.AllAg.Embryonic_pancreas mm9 No description Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.10.AllAg.Embryonic_pancreas.bed ...

  1. File list: InP.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.10.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.10.AllAg.Embryonic_pancreas.bed ...

  2. File list: InP.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.20.AllAg.Embryonic_pancreas mm9 Input control Embryo Embryonic pancreas SRX...287026 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.20.AllAg.Embryonic_pancreas.bed ...

  3. File list: NoD.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.05.AllAg.Embryonic_pancreas mm9 No description Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Emb.05.AllAg.Embryonic_pancreas.bed ...

  4. File list: Oth.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Emb.20.AllAg.Embryonic_pancreas mm9 TFs and others Embryo Embryonic pancreas SR...X287023,SRX287022,SRX287021,SRX287020,SRX287016,SRX287017 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.20.AllAg.Embryonic_pancreas.bed ...

  5. File list: Oth.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development

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    Chien-Hsun Huang

    2017-09-01

    Full Text Available Rhein, a glucoside chemical compound found in a traditional Chinese medicine derived from the roots of rhubarb, induces cell apoptosis and is considered to have high potential as an antitumor drug. Several previous studies showed that rhein can inhibit cell proliferation and trigger mitochondria-related or endoplasmic reticulum (ER stress-dependent apoptotic processes. However, the side effects of rhein on pre- and post-implantation embryonic development remain unclear. Here, we show that rhein has cytotoxic effects on blastocyst-stage mouse embryos and induces oxidative stress and immunotoxicity in mouse fetuses. Blastocysts incubated with 5–20 μM rhein showed significant cell apoptosis, as well as decreases in their inner cell mass cell numbers and total cell numbers. An in vitro development assay showed that rhein affected the developmental potentials of both pre- and post-implantation embryos. Incubation of blastocysts with 5–20 μM rhein was associated with increased resorption of post-implantation embryos and decreased fetal weight in an embryo transfer assay. Importantly, in an in vivo model, intravenous injection of dams with rhein (1, 3, and 5 mg/kg body weight/day for four days resulted in apoptosis of blastocyst-stage embryos, early embryonic developmental injury, and decreased fetal weight. Intravenous injection of dams with 5 mg/kg body weight/day rhein significantly increased the total reactive oxygen species (ROS content of fetuses and the transcription levels of antioxidant proteins in fetal livers. Additional work showed that rhein induced apoptosis through ROS generation, and that prevention of apoptotic processes effectively rescued the rhein-induced injury effects on embryonic development. Finally, the transcription levels of the innate-immunity related genes, CXCL1, IL-1 β and IL-8, were down-regulated in the fetuses of dams that received intravenous injections of rhein. These results collectively show that rhein has

  11. Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves.

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    Yin Liu

    Full Text Available Nitric oxide synthase-3 (NOS3 has recently been shown to promote endothelial-to-mesenchymal transition (EndMT in the developing atrioventricular (AV canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT and NOS3(-/- mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3(-/- compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3(-/- mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1(+ cells in the AV cushion were decreased in NOS3(-/- compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ, bone morphogenetic protein (BMP2 and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3(-/- compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency.

  12. Intact calcium signaling in adrenergic-deficient embryonic mouse hearts.

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    Peoples, Jessica N; Taylor, David G; Katchman, Alexander N; Ebert, Steven N

    2018-01-22

    Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh -/- ) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10.5 (E10.5). To test this hypothesis, we used ratiometric fluorescent calcium imaging techniques to measure cytosolic calcium transients, [Ca 2+ ] i in isolated E10.5 mouse hearts. Our results show that spontaneous [Ca 2+ ] i oscillations were intact and robustly responded to a variety of stimuli including extracellular calcium (5 mM), caffeine (5 mM), and NE (100 nM) in a manner that was indistinguishable from controls. Further, we show similar patterns of distribution (via immunofluorescent histochemical staining) and activity (via patch-clamp recording techniques) for the major voltage-gated plasma membrane calcium channel responsible for the L-type calcium current, I Ca,L , in adrenergic-deficient and control embryonic cardiac cells. These results demonstrate that despite the absence of vital adrenergic hormones that consistently leads to embryonic lethality in vivo, intracellular and extracellular calcium signaling remain essentially intact and functional in embryonic mouse hearts through E10.5. These findings suggest that adrenergic stimulation is not required for the development of intracellular calcium oscillations or extracellular calcium signaling through I Ca,L and that aberrant calcium signaling does not likely contribute

  13. Proteomic Analysis of Chicken Skeletal Muscle during Embryonic Development

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    Hongjia Ouyang

    2017-05-01

    Full Text Available Embryonic growth and development of skeletal muscle is a major determinant of muscle mass, and has a significant effect on meat production in chicken. To assess the protein expression profiles during embryonic skeletal muscle development, we performed a proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ in leg muscle tissues of female Xinghua chicken at embryonic age (E 11, E16, and 1-day post hatch (D1. We identified 3,240 proteins in chicken embryonic muscle and 491 of them were differentially expressed (fold change ≥ 1.5 or ≤ 0.666 and p < 0.05. There were 19 up- and 32 down-regulated proteins in E11 vs. E16 group, 238 up- and 227 down-regulated proteins in E11 vs. D1 group, and 13 up- and 5 down-regulated proteins in E16 vs. D1 group. Protein interaction network analyses indicated that these differentially expressed proteins were mainly involved in the pathway of protein synthesis, muscle contraction, and oxidative phosphorylation. Integrative analysis of proteome and our previous transcriptome data found 189 differentially expressed proteins that correlated with their mRNA level. The interactions between these proteins were also involved in muscle contraction and oxidative phosphorylation pathways. The lncRNA-protein interaction network found four proteins DMD, MYL3, TNNI2, and TNNT3 that are all involved in muscle contraction and may be lncRNA regulated. These results provide several candidate genes for further investigation into the molecular mechanisms of chicken embryonic muscle development, and enable us to better understanding their regulation networks and biochemical pathways.

  14. G-quadruplexes as novel cis-elements controlling transcription during embryonic development.

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    David, Aldana P; Margarit, Ezequiel; Domizi, Pablo; Banchio, Claudia; Armas, Pablo; Calcaterra, Nora B

    2016-05-19

    G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional role in vivo during vertebrate embryonic development has not yet been addressed. Here, we performed an in silico search to find conserved putative G-quadruplex sequences (PQSs) within proximal promoter regions of human, mouse and zebrafish developmental genes. Among the PQSs able to fold in vitro as G-quadruplex, those present in nog3, col2a1 and fzd5 promoters were selected for further studies. In cellulo studies revealed that the selected G-quadruplexes affected the transcription of luciferase controlled by the SV40 nonrelated promoter. G-quadruplex disruption in vivo by microinjection in zebrafish embryos of either small ligands or DNA oligonucleotides complementary to the selected PQSs resulted in lower transcription of the targeted genes. Moreover, zebrafish embryos and larvae phenotypes caused by the presence of complementary oligonucleotides fully resembled those ones reported for nog3, col2a1 and fzd5 morphants. To our knowledge, this is the first work revealing in vivo the role of conserved G-quadruplexes in the embryonic development, one of the most regulated processes of the vertebrates biology. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

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    Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

    2017-01-01

    Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

  16. Primordial dwarfism gene maintains Lin28 expression to safeguard embryonic stem cells from premature differentiation.

    Science.gov (United States)

    Dai, Qian; Luan, Guangxin; Deng, Li; Lei, Tingjun; Kang, Han; Song, Xu; Zhang, Yujun; Xiao, Zhi-Xiong; Li, Qintong

    2014-05-08

    Primordial dwarfism (PD) is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7) have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb). Here, we show that Larp7 deficiency likely does not significantly increase P-TEFb activity. We further discover that Larp7 knockdown does not affect pluripotency but instead primes embryonic stem cells (ESCs) for differentiation via downregulation of Lin28, a positive regulator of organismal growth. Mechanistically, we show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability. We propose that proper regulation of Lin28 and PTEFb is essential for embryonic cells to achieve a sufficient number of cell divisions prior to differentiation and ultimately to maintain proper organismal size. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Differential radiosensitivity of mouse embryonic neurons and glia in cell culture

    International Nuclear Information System (INIS)

    Dambergs, R.; Kidson, C.

    1977-01-01

    The responses of neurons and glial cells to ultraviolet and γ-radiation were studied in cell cultures of embryonic mouse brains. A decrease in the ratio of glia to neurons occurred after both forms of irradiation. [ 3 H]thymidine labelling followed by autoradiography revealed that all glia were capable of replication, whereas 70 percent of neurons were non-replicating under the conditions of the study. Ultraviolet radiation caused a decrease in the proportion of replicating neurons but did not affect the proportion of replicating glia, whereas γ-radiation caused a decrease in DNA replication in both cell types. Levels of ultraviolet radiation-induced unscheduled DNA synthesis were lower in neurons than in glia. It is concluded that sensitivity to both ionizing and ultraviolet radiation of neurons and glial cells in embryonic brain cultures is determined primarily by the capacity for and state of DNA replication. Neurons which have already reached the stage of terminal differentiation are more resistant than replicating neurons of glial cells

  18. Tetraploid Embryonic Stem Cells Maintain Pluripotency and Differentiation Potency into Three Germ Layers.

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    Hiroyuki Imai

    Full Text Available Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

  19. Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons

    International Nuclear Information System (INIS)

    Kyriakis, J.M.; Hausman, R.E.; Peterson, S.W.

    1987-01-01

    The effect of insulin on the appearance of the enzyme choline acetyltransferase in embryonic chicken retina neurons cultured in defined medium was studied. In the presence of a minimal level of insulin (1 ng/ml), ChoAcT activity increased with time in culture. A correspondence between the insulin concentration in the defined medium (1-100 ng/ml) and both the rate of increase and maximum attained level of ChoAcT activity was observed. Maximal ChoAcT activity was 2- to 3-fold greater in cells cultured in the presence of 100 ng of insulin per ml than in cells cultured in the presence of 1 ng of insulin per ml. To elicit maximum ChoAcT activity, insulin at 100 ng/ml was required in the medium for only the first 4 days of the culture period, at which time insulin could be reduced to maintenance levels (10 ng/ml) without affecting ChoAcT activity. Insulin binding assays performed during a 7-day culture period revealed that irrespective of the 125 I-insulin concentration in the medium during culture, cell-surface insulin receptors decreased by ≅ 90% between 4 and 7 days in culture. This decrease in insulin binding corresponded to the observed decrease in the sensitivity of ChoAcT activity to insulin. The findings suggest that insulin plays a role in mediating cholinergic differentiation in the embryonic chicken retina

  20. Melatonin prevents postovulatory oocyte aging and promotes subsequent embryonic development in the pig.

    Science.gov (United States)

    Wang, Tao; Gao, Ying-Ying; Chen, Li; Nie, Zheng-Wen; Cheng, Wei; Liu, Xiaoyan; Schatten, Heide; Zhang, Xia; Miao, Yi-Liang

    2017-06-26

    Oxidative stress is known as a major contributing factor involved in oocyte aging, which negatively affects oocyte quality and development after fertilization. Melatonin is an effective free radical scavenger and its metabolites AFMK and AMK are powerful detoxifiers that eliminate free radicals. In this study, we used porcine oocytes to test the hypothesis that melatonin could scavenge free radicals produced during oocyte aging, thereby maintaining oocyte quality. We compared reactive oxygen species levels, apoptosis levels, mitochondrial membrane potential ratios, total glutathione contents and expression levels in fresh, aged and melatonin-treated aged porcine oocytes and observed the percentage of blastocyst formation following parthenogenetic activation. We found that melatonin could effectively maintain the morphology of oocytes observed in control oocytes, alleviate oxidative stress, markedly decrease early apoptosis levels, retard the decline of mitochondrial membrane potential and significantly promote subsequent embryonic development in oocytes aged for 24 hr in vitro . These results strongly suggest that melatonin can prevent postovulatory oocyte aging and promote subsequent embryonic development in the pig, which might find practical applications to control oocyte aging in other mammalian species including humans to maintain the quality of human oocytes when performing clinical assisted reproductive technology.