Dissertations / Theses: 'Digoxin'

1

Alexandrovich, Susan K. "Characterization of monoclonal antibodies against digoxin /." Online version of thesis, 1987. http://hdl.handle.net/1850/10681.

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Matthewson, Beryl Ellen. "Digoxin-like immunoreactive substances in the neonate." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/28022.

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Digoxin, a steroidal glycoside that inhibits Na⁺/K⁺-ATPase, is the most commonly prescribed cardiac medication in North America. Blood levels of this drug are routinely measured to reduce the risks of toxicity. Reports questioning the specificity of antisera used in radioimmunoassays for serum digoxin measurements began to appear after 1975¹ when plasma from patients with renal failure, not on glycoside therapy, showed false-positive digoxin levels. Since then, digoxin-like immunoreactive substances (DLIS) have been found in sera from patients with hepatic failure, hypertension, pre-eclampsia, in amniotic fluid and cord blood. Some of the highest values for DLIS have been detected in premature infants, where levels have often exceeded the therapeutic range (0.2-2.0 µg/L) for digoxin. Cord blood has been identified as a rich source of DLIS. Dahl et al² were the first to suggest that a circulating saluretic substance "endoxin", may cause hypertension in salt sensitive rats. Gruber et al³ reported on the existence of digoxin-like factor(s) in the plasma of volume-expanded dogs. Plasma from these dogs inhibited Na⁺/K⁺ATPase activity. A number of other studies have supported the concept that such digoxin-like factors may be of etiological significance in hypertension⁴. In view of these observations, a study was undertaken to isolate and fractionate DLIS from mixed cord blood and determine whether or not any of this digoxin-like material possessed Na⁺/K⁺-ATPase inhibitory properties. Cord blood collected in the Grace Hospital Maternity Unit (Vancouver, BC), was pooled and DLIS extracted using C₁₈,R-Sep Paks. Extracts were resolved by high performance liquid chromatography (HPLC) into several fractions containing digoxin equivalent immunoactivity as measured by radioimmunoassay (RIA). A number of steroids and bile acids (dehydroepi-androsterone-sulfate, cortisone, Cortisol, deoxycortisone, ∆⁴androstene-dione, progesterone and glycochenodeoxycholic acid) cross-reacted with digoxin antisera and had HPLC retention times similar to DLIS-containing fractions. The ability of HPLC generated DLIS positive cord blood fractions to inhibit Na⁺/K⁺-ATPase activity was determined in three different assay systems; red cell ⁸⁶Rb uptake canine kidney-Na⁺/K⁺-ATPase and red cell membrane-Na⁺/K⁺-ATPase. At least six fractions contained DLIS and inhibited Na⁺/K⁺-ATPase activity. Inhibition varied with the assay system used but none of the fractions inhibited ⁸⁶Rb uptake by erythocytes. One fraction (which eluted at 29 minutes) contained progesterone; 72% of the inhibitory activity present in this fraction was attributable to this steroid. Another inhibitory fraction co-eluted with dehydroepiandrosterone-sulfate (DHEAS-S). The only fractions found to inhibit both the red cell membrane and canine kidney Na⁺ /K⁺-ATPase enzymes eluted at 7 and 29 minutes. In summary, a number of digoxin-like immunoreactive substances were isolated from cord blood by HPLC fractionation and found to inhibit Na⁺/K⁺-ATPase activity. Inhibition varied with the assay system used. There was no apparent correlation between inhibition and digoxin immunoreactivity. Very large quantities (500 mL) of cord blood were extracted to demonstrate these properties. It remains to be determined whether or not DLIS isolated during the perinatal period is of physiological significance.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

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3

Hui, James. "Analysis for digoxin and metabolites in serum and digoxin disposition in the elderly with gastrointestinal disease after two oral dosage forms /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487587604130428.

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4

Hallberg, Pär. "Pharmacogenomics of antihypertensive treatment & clinical pharmacological studies of digoxin treatment /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5782.

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5

Cavet, Megan Elizabeth. "Intestinal secretion of organic solutes." Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318538.

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Svensson, Åsa. "Applications of a new logic to old drugs: angiogenesis inhibition in neuroblastoma /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3458.

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7

BARROS, Isabel Cristina Medeiros. "Monitoração terapêutica das concentrações plásmaticas da digoxina em pacientes com insuficiência cardíaca." Universidade Federal de Goiás, 2008. http://repositorio.bc.ufg.br/tede/handle/tde/1703.

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Made available in DSpace on 2014-07-29T15:29:05Z (GMT). No. of bitstreams: 1 dissertacao isabel cristina.pdf: 549593 bytes, checksum: ff591d0e143ca66263716f60188e9801 (MD5) Previous issue date: 2008-10-27
It was investigated the clinical, lab and plasma digoxin concentration profiles in 15 cardiac heart failure (CHF) outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital. It was aimed to know plasma digoxin concentration profile in 15 cardiac heart failure (CHF) outpatients by two analytical methods, taking account clinical, laboratorial, habits, anthropometric data and drug usage. Digoxin dosage was developed by LC/MS/MS and immunoassay methods; questionnaire and consults handbooks were performed. Results and Conclusions: 87% of the patients who over 46 years of age (33% above 61), the masculine majority; the IC of Chagas disease origin presented greater occurrence, followed of the hipertensive and idiopatic (59%); IC functional classroom II (53.33%); hypertension and diabetes had been distinguished as co-morbidities (26.67% and 20%); tobaccoism, overweight and obesity degree I had presented low occurrence. No patients presented relevant clinical data suggestive of digitalis intoxication. No observed changes in biochemical and hematological exams. The ejection fractions were good by means 41.7 ± 9%. Some drugs with interaction potential had been associated to the treatment, apparently without alterations. Statistical significative difference between both methods was observed (P < 0.05, ANOVA, Tukey Test). In the immunoassay method, all the patients were inside of the therapeutical range (0, 5-2, 0 ng/mL), whereas for the LC-MS/MS method, 8 patients they would be in subtherapeutical concentrations. However, no patient presented signals or symptoms of poisoning or inefficacy of the digoxin, demonstrating biological variability. The two methods are useful, since that it has a correlation with the clinical and laboratorial state of the patients.
Investigou-se o perfil clínico, laboratorial e as concentrações de digoxina plasmática em 15 pacientes com insuficiência cardíaca (IC) atendidos no Ambulatório de Insuficiência Cardíaca do HC-UFG. Objetivou-se estudar o perfil de concentrações plasmáticas de digoxina em pacientes com IC, utilizando dois métodos analíticos, e descrever a digoxinemia considerando os dados clínicos, laboratoriais, hábitos, IMC e consumo de medicamentos. A metodologia utilizada consistiu de cromatografia líquida de alta eficiência acoplada a espectrometria de massas (LC/MS/MS) e Imunoensaio, aplicação de questionário e consulta a prontuários. Como resultados, observou-se: 87% dos pacientes maiores que 46 anos de idade (33% acima de 61), a maioria masculina, a IC de origem chagásica apresentou maior ocorrência, seguida da hipertensiva e idiopática (59%); IC classe funcional II (53,33%); hipertensão e diabetes destacaram-se como co-morbidades (26,67% e 20%); tabagismo, sobrepeso e obesidade grau I apresentaram baixa ocorrência. Nenhum dos pacientes apresentou dados clínicos relevantes sugestivos de intoxicação digitálica. Não houve alterações em exames bioquímicos e hematológicos. A fração de ejeção média foi 41,7 ± 9%, portanto nenhum paciente apresentou FE como preditor de mau prognóstico. Vários fármacos com potencial de interação estiveram associados ao tratamento, aparentemente sem alterações. Houve diferença significativa (P < 0,05, ANOVA, Teste de Tukey) entre os métodos analíticos. No método de imunoensaio, todos os pacientes estavam dentro da faixa terapêutica (0,5-2,0 ng/mL), enquanto que pelo método LC-MS/MS, 8 pacientes estariam em sub-dosagens. Entretanto, nenhum paciente apresentou sinais ou sintomas de intoxicação ou de ineficácia da digoxina, demonstrando variabilidade biológica. Os dois métodos são úteis, desde que haja uma correlação com o estado clínico e laboratorial dos pacientes.

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8

Embree, Leanne. "Development of a sensitive, quantitative high-performance liquid chromatographic assay for the measurement of digoxin in patient groups with high levels of digoxin-like immunoreactive substances." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/29093.

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Digoxin is the most commonly used digitalis glycoside for the treatment of congestive heart failure and certain disturbances of cardiac rhythm. The low therapeutic index observed for digoxin and the clinical significance of digoxin therapy have necessitated the development of sensitive analytical methods for the quantitation of digoxin in biological samples. Digoxin may be analysed by several methods including immunoassays, chromatographic procedures and various biological and chemical methods. Immunoassays, both radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) procedures, are used in the clinical laboratory because of their speed, precision, sensitivity and relatively low cost. However, reaction of the digoxin antibodies used in the immunoassay methods with digoxin metabolites, endogenous compounds such as digoxin-like immunoreactive substances (DLIS), and other drugs that may be co-administered with digoxin continues to be a major problem. The lack of specificity of the immunoassay methods for digoxin has led to difficulties in interpretation of assay values. Attempts to compensate for this lack of specificity have included the use of chromatographic systems as elaborate sample handling methods prior to immunoassay. However, since an immunoassay was used for detection of digoxin in these techniques, the specificity may still be quest ionable. A sensitive and specific assay for digoxin using physico-chemical methods for measurement is therefore needed. A method was developed using pre-column derivatization of digoxin and its metabolites with 3,5-dinitrobenzoyl chloride followed by HPLC analysis with electrochemical detection. A maximum sensitivity of 0.883 ng of 3,5-dinitrobenzoyl digoxin (0.394 ng digoxin) was observed using dual electrode detection in the redox mode. Although resolution between derivatized digoxin and its metabolites was obtained, the low yield of the digoxin derivative and the formation of metabolites when small (ng) samples were derivatized made this method unsuitable for evaluating patient samples. A high-performance liquid chromatographic (HPLC) assay using post-column derivatization of digoxin, which separated digoxin from its metabolites and some commonly coadministered drugs, was developed. Post-column (PC) derivatization of digoxin with concentrated hydrochloric acid and dehydroascorbic acid, followed by fluorescence detection, allowed for quantitation within the therapeutic range of digoxin. Steroids which have been reported to cross-react with digoxin antisera were assayed using the HPLC-PC method developed in this study. The steroid samples either did not elute from the HPLC system or did not produce a fluorescent product under these conditions. Serum samples from digitalized patients were evaluated using both the HPLC-PC and the FPIA methods. When compared to the HPLC procedure, the FPIA assay results gave, on average, higher digoxin levels. This may have been due to the inclusion of digoxin metabolites or endogenous compounds with the FPIA assay. Serum samples from undigitalized patient groups where high DLIS levels have been reported were also evaluated. These included umbilical cord blood samples and samples from hypertensive patients, renal failure patients and hepatic failure patients. Comparison of the HPLC-PC and FPIA methods demonstrated that the HPLC-PC assay gave fewer false positive results than the FPIA. The HPLC-PC assay developed for analysis of digoxin was unaffected by the presence of digoxin metabolites, numerous steroids, co-administered drugs and endogenous compounds, most of which have been reported to give false positive results with the FPIA.
Pharmaceutical Sciences, Faculty of
Graduate

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9

Hallberg, Pär. "Pharmacogenomics of Antihypertensive Treatment & Clinical Pharmacological Studies of Digoxin Treatment." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5782.

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In Part I we found that the CYP2C9 genotype appears to influence the diastolic blood pressure response to the angiotensin II-receptor antagonist irbesartan in patients with hypertension and left ventricular hypertrophy. Those with the *1/*2 genotype (slower metabolism) responded better than those with the *1/*1 genotype (normal metabolism), likely due to a slower elimination of the drug. We further found that a +9/-9 exon 1 polymorphism of the B2 bradykinin receptor gene – shown to affect mRNA expression - appears to influence the regression of left ventricular mass during therapy with irbesartan or the beta-blocker atenolol in the same patients. Subjects with the -9/-9 genotype (higher mRNA expression) had a greater regression than carriers of the +9 allele. In Part II we found that women on digoxin therapeutic drug monitoring have higher serum digoxin concentrations (SDCs) as compared to men (1.54±0.04 [nmol/L±SE] vs 1.20±0.05 [nmol/L±SE], p<0.001), which could be of importance since an SDC >1.4 nmol/L has been associated with increased mortality. We further found that coadministration of P-glycoprotein inhibitors with digoxin was common (47%) among the same patients, and that the SDC increased in a stepwise fashion with the number of P-glycoprotein inhibitors (20-60%). Lastly, we found that patients admitted to Swedish coronary care units with atrial fibrillation without heart failure and who had been given digoxin had a higher 1-year mortality than those not given digoxin (RR 1.44 [95% CI 1.29-1.60], adjustment made for potential confounders). In conclusion, Part I represents a further step in the pharmacogenomic prospect of tailoring antihypertensive therapy. Part II indicates that heightened attention to the digoxin-dose is warranted in women, that there is a need for awareness about P-glycoprotein interactions with digoxin, and that long-term therapy with digoxin is an independent risk factor for death among patients with atrial fibrillation without heart failure.

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Vetticaden, Santosh John. "Evaluation of Analytical, Pharmacokinetic and Pharmacodynamic Methods for the Study of Digoxin." VCU Scholars Compass, 1985. http://scholarscompass.vcu.edu/etd/5103.

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The primary objective of the research was to investigate the pharmacodynamics of digoxin in dogs. Initially an assay specific for digoxin in the presence of its major metabolites, viz., digoxigenin, digoxigenin mono-digitoxoside, digoxigenin bis-digitoxoside and dihydrodigoxin was developed using HPLC-RIA. Methodology for non-invasive measurement of left ventricular ejection time (LVET) and other systolic time intervals (STI) in beagle dogs were developed. This involved surgery for exteriorization of the carotid artery in the dogs and subsequent measurements of LVET and STI after recovery. STI, heart rate (HR) and digoxin levels were monitored in normal beagle dogs administered 0.05 mg/kg or 0.025 mg/kg i.v., infused uniformly over a 5 min. period. The STI did not lend itself to pharmacodynamic modelling. The LVET, QS2 and P-R interval were found to be inversely, but linearly, related to the heart rate. Therefore, the bradycardic response to digoxin was extensively investigated in beagle dogs. Pharmacodynamic models evaluated for modelling the bradycardic response to digoxin were: the pharmacokinetic model with a direct linear link, the linear model, the physiologic-pharmacokinetic model with direct linear link and the effect compartment model. The physiologic pharmacokinetic model was simulated using SPICE2 which uses network thermodynamics to simulate biological systems. Criteria for the selection of appropriate models were established. Using the established criteria, the effect compartment model was demonstrated to be the best model. The implications and applications of pharmacodynamic models in general and specifically of the pharmacodynamic model for the bradycardic response to the digoxin are discussed.

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Murata, Viviane Midori. "Produção e caracterização da porção Fab do anticorpo anti-digoxina utilizando a tecnologia de phage display." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-11062012-083314/.

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A digoxina é um medicamento usado para tratar distúrbios cardíacos, com janela terapêutica muito estreita. Para combater seu efeito tóxico, fragmentos Fab do anticorpo policlonal anti-digoxina estão disponíveis comercialmente. Nosso objetivo foi a obtenção de variantes de fragmentos Fab do anticorpo monoclonal anti-digoxina usando a tecnologia phage display, que permite gerar fragmentos de anticorpos de alta afinidade e especificidade. Uma biblioteca combinatória de fragmentos Fab anti-digoxina foi construída no vetor pComb3X a partir do RNA total do hibridoma anti-digoxina. Seis clones foram isolados, todos com sequência idêntica na cadeia pesada. A cadeia leve apresentou 2 clones idênticos, um pseudogene e um clone com um aminoácido distinto no CDR2. Quatro clones apresentando variações na sequência do framework1 da cadeia leve foram expressos como fragmentos Fab solúveis. Todos apresentaram ligação à digoxina-BSA por ELISA e Western blotting. A ligação específica do anticorpo também foi confirmada pelo BIAcore, que permitiu ranqueamento entre os clones.
Digoxin is a pharmaceutical used in the control of cardiac dysfunction. Its therapeutic window is very narrow. To counteract the toxic effect, polyclonal anti-digoxin Fab fragments are commercially available. Our goal was to obtain variants of monoclonal anti-digoxin Fab fragments by phage display technology, which allows the generation of high affinity and specificity antibody fragments. Anti-digoxin Fab fragments combinatorial library was constructed into pComb3X vector from total RNA of anti-digoxin hybridoma. Six clones were isolated and the heavy chain presented the same sequence. For the light chain, 2 clones were identical, one was a pseudogene and other one presented a distinct amino acid in the CDR2. Four clones presenting variations in the framework 1 were induced to express soluble Fab fragments, all positive for anti-digoxin binding in ELISA assays and Western blotting. The specific binding of the antibody was further confirmed by BIAcore, which allowed ranking of the clones.

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Tzou, Meir-Chyun. "Development and validation of a specific high performance liquid chromatographic method for determination of digoxin and metabolites in serum and its applications to digoxin metabolism and therapeutic drug monitoring studies in humans /." The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487854314873705.

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Baek, Myoungki. "Dynamic system analysis of receptor interaction and effectuation mechanisms of digoxin in the rat heart." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975656562.

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Weitkamp, Christine. "Warum zeigen die Herzglykoside Ouabain und Digoxin unterschiedliche Kreislaufwirkung? Charakterisierung eines mutmasslichen Herzglykosid-Bindungsproteins im Serum und Analyse der Wirkung beider Steroide auf die Endothelin-1- und NO-Freisetzung aus arteriellen Endothelzellen /." Wettenberg : VVB Laufersweiler, 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976405792.

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Gashi, Elida. "Hur påverkar johannesört farmakokinetiken utav warfarin, ciklosporin, digoxin, preventivmedel och teofyllin? Vad har detta för klinisk betydelse?" Thesis, Linnéuniversitetet, Institutionen för naturvetenskap, NV, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-18745.

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St. John’s wort extract is composed of a large number of components, about 150, but the most studied and interesting substance are hyperforin and hypericin. The herb is very popular and it is known for its pharmacological efficacy in numerous disorders. It is used for treatment of mild to moderated depression as an alternative to synthetic antidepressants. The St. John’s wort products are available in several preparations, as tablets, capsules, tea, fresh plant juice etc. Hyperforin is the part of St. John’s wort that gives the antidepressant effect through inhibition of reuptake of neurotransmitters such norepinephrine, serotonin, dopamine, GABA and L-glutamate.Since 1999, several case reports and clinical studies have demonstrated the interactions of St. John’s wort extract with other medical products, resulting in a decreased plasma concentration and potential therapeutics failure. The mechanism behind this is an interaction between St. John’s wort with intestinal and hepatic cytochrome P450 and P-glycoprotein, resulting in inducing these enzymes. In vitro investigations indicated that this induction is medicated by an interaction of hyperforin with the pregnane X receptor.Long-term co-medication of St. John’s wort extract reduces the bioavailability of wide variety of drugs, including digoxin, warfarin, cyclosporine, oral contraceptive and theophylline.The object of the present thesis was to investigate and describe the influence of St. John’s wort extract on the pharmacokinetics of the drugs mentioned above and what this pharmacokinetic interaction has for clinical consequences.Seven studies, with different numbers of participants, performed in different countries, were compiled to describe the effect of St. John’s wort on the drugs.The results from these studies showed that St. John’s wort extract affects the metabolism of these drugs by significant reducing theirs pharmacological effect. This decrease of the bioavailability and plasma concentration can be the results of intestinal and hepatic induction of CYP enzymes and p-glycoprotein. From these results I conclude that St. John’s wort should be used with caution and patients receiving these drugs should regularly monitory theirs plasma concentration.

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Inocencio, André Luís. "Purificação e caracterização do fragmento Fab anti-digoxina obtido pela técnica de phage display." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-25082016-085639/.

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A digoxina é um dos medicamentos indicados para o tratamento de falência cardíaca. Possui janela terapêutica estreita, sendo responsável por casos de intoxicação. O único antídoto disponível para a desintoxicação é o anticorpo policlonal DigiFab®, no formato Fab. O seu uso é eficaz, porém de custo elevado. Clones bacterianos produtores de fragmento Fab monoclonal anti-digoxina foram obtidos previamente pelo nosso grupo, pela técnica de phage display. Neste trabalho as variantes Fab dos 4 clones foram expressas em E.coli para estabelecer o método para a purificação. Com a obtenção dos fragmentos Fab purificados, foi caracterizada a sua afinidade ao antígeno e especificidade, em ensaios de inibição por digoxina, digitoxina, digoxigenina e ouabaina. Os parâmetros cinéticos da ligação dos fragmentos Fab dos 4 clones e do DigiFab® foram avaliados por SPR. Nas condições experimentais, não foram verificadas diferenças significativas entre os produtos dos 4 clones e o comercial, demonstrando o potencial dos fragmentos Fab monoclonais obtidos como antídoto à digoxina.
Digoxin is a medication indicated for heart failure treatment. Its therapeutic window is narrow, being responsible for intoxication cases. The only antidote available for the detoxification is a polyclonal antibody - DigiFab® in Fab format. Its use is effective, but costly. Bacterial clones producing anti-digoxin monoclonal Fab fragments were previously obtained by our group using phage display technology. In this work the Fab variants of the 4 clones were expressed in E.coli to establish the purification method. The purified fragments were characterized regarding the affinity to the antigen and the specificity through inhibition assays with digoxin, digitoxin, digoxigenin and ouabain. The binding kinetic parameters of Fab fragments of the 4 clones and the commercial product to Dig-BSA conjugate were assessed by SPR. Under the experimental conditions no significant differences were observed among the 4 clones and the commercial product, demonstrating the potential of monoclonal Fab fragments as an antidote to digoxin.

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Meseg, Antje [Verfasser]. "Einfluss von Polymorphismen im Multidrug resistance Gen Typ 1 (ABCB1) auf die Single dose Kinetik von Digoxin / Antje Meseg." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1022941127/34.

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Hopoate-Sitake, Moana Lee. "A Novel Use of Digoxin Immune Fab Fragment in Identification and Isolation of an Endogenous Digitalis-like Factor Found in Preeclampsia." BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/2599.

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The mechanisms mediating the hypertension of preeclampsia (PE) are unclear. Endogenous digitalis-like factors (EDLFs) are specific sodium pump (SP) inhibitors implicated in essential and experimental hypertension, but they have not been fully explored in the setting of PE. This study uses a digoxin antibody Fab fragment to address the question of whether such factors are present and increased in PE, to investigate a possible treatment of PE, and to isolate and characterize all EDLFs present in PE. Sera and placenta from women with PE did show a significant increase in SP inhibition in comparison to women with normal pregnancy and Digibind® was found to bind EDLFs and essentially block or reverse SP inhibition. Sera were collected in a Phase II, double-blind, placebo controlled clinical study in which women with severe preeclampsia were dosed with Digibind®, as a therapeutic, and the SP activity measured. Sera and placenta from women with PE was also investigated for their inhibitory effects on the SP. Known candidates for EDLFs were investigated for their SP inhibitory effects, as well as how digitalis antibody immune Fab fragments, Digibind® and DigiFab™, bound them and affected the SP activity. Digibind® is also a sufficient affinity material used to isolate and purify PE EDLFs. Additionally, the placentas of preeclamptic women have high levels of similar EDLFs. These studies provide evidence for the existence of EDLFs that circulate in women with PE, and Digibind® is an effective and novel tool to bind, isolate and purify EDLFs in PE.

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Svensson, Åsa. "Application of a New Logic to Old Drugs: Angiogenesis Inhibition in Neuroblastoma." Doctoral thesis, Uppsala University, Department of Medical Cell Biology, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3458.

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Neuroblastoma is one of the most common solid cancers of early childhood. In Sweden, approximately 10-15 cases occur annually. The overall five-year neuroblastoma survival in Europe is approximately 45%. Since cancer treatment involves drugs with risks of side effects in the growing child, there is a need for more effective and less toxic drugs. One new approach in cancer treatment is inhibition of tumor angiogenesis, i.e., of new blood vessel growth into the tumor. An angiogenesis inhibitor may be combined with cytostatic drugs to enhance the efficacy. The aim of this study was to investigate how drugs could be used to inhibit angiogenesis and tumor growth in a xenograft model of human neuroblastoma in nude mice.

The tumors express the angiogenesis stimulator vascular endothelial growth factor (VEGF) on both protein and mRNA levels. The angiogenesis inhibitors SU5416 (an inhibitor of VEGF signalling) and TNP-470 (an inhibitor of endothelial cell proliferation) inhibited angiogenesis in our model. TNP-470, however, inhibited angiogenesis without significant reduction of the tumor growth, in contrast to SU5416.

We also discovered that the cytostatic drug CHS 828 could cause regression of neuroblastoma tumors in the model when given orally at a low daily dose, alone or in combination with the angiogenesis inhibitor SU5416 or TNP-470.

Furthermore, a new use of the cardiac glycoside digoxin was found. Digoxin inhibited FGF-2 -stimulated bovine capillary endothelial cell growth in vitro, and inhibited angiogenesis in vivo in the chick chorioallantoic membrane assay (CAM). It also inhibited neuroblastoma growth by approximately 50% in our neuroblastoma model.

In conclusion, CHS 828 and digoxin represent two classes of drugs with potent antitumor effects that may be valuable in treatment of neuroblastoma, either alone or in combination with angiogenesis inhibitors.

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Ma, Jie. "Human Endogenous Sodium Pump Inhibitors Measurement, Source, Synthesis and Regulation." BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/2953.

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The sodium pump (SP or Na+,K+-ATPase) is a membrane embedded protein complex that pumps 3 sodium ions out and 2 potassium ions into the cell per cycle and in so doing creates a cell membrane electrochemical potential. The membrane potential is critical for any functional cell. In the vasculature, reduction in the voltage potential causes vascular smooth muscle contraction and a narrowing of blood vessels (vasoconstriction) which can lead to increased blood pressure (hypertension). Substantial research over the past several decades has provided a vast amount of research on SP inhibitors, sometimes called endogenous digitalis-like factors (EDLF). Increased levels of these factors have been implicated in many hypertensive disorders including preeclampsia (PE), a life-threatening complication of pregnancy. It has been demonstrated that EDLF might be a causative factor in the pathophysiology of hypertension in PE. In order to elucidate EDLF production and regulation in PE, We developed a radioimmunoassay (RIA) measuring EDLF that could be applied to serum from pregnant women, placental homogenate and placental tissue culture. This assay employs Digibind, a commercially available Fab fragment derived from polyclonal antidigoxin antibodies that cross reacts with EDLF, as the primary antibody. Using Digibind RIA, we demonstrated that placenta is a source of EDLF production and regulation. Moreover, the identification of an inhibitor, ketoconazole and a substrate, 17-hydroxyprogesterone of the synthetic pathway of EDLF in placenta proved that this pathway shares steps with the steroid synthetic pathway. Some potential regulatory agents which have elevated levels in PE or be associated in PE and thus are thought to mediate PE, such as hydrogen peroxide, tumor necrosis factor-α (TNF-α) and hypoxia have also been demonstrated to be stimuli of EDLF production in placenta. These findings are helpful to the further study on EDLF synthesis and regulation in placenta. Once we elucidate the mechanisms, it could be easier to provide deeper insights into the pathogenesis of PE and subsequently develop earlier diagnosis and effective prevention of or therapeutic approaches to PE.

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Neves, Claodete Hasselstrom. "Efeitos da administração crônica da digoxina e do verapamil sobre o desempenho físico e a estrutura e função cardíaca em ratos submetidos ao treinamento físico intervalado." Universidade Federal de Mato Grosso, 2015. http://ri.ufmt.br/handle/1/682.

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O objetivo deste estudo foi investigar os efeitos da administração crônica de digoxina e do verapamil durante treinamento físico intervalado de alta intensidade (TFI) sobre o desempenho físico, capacidade funcional e morfologia cardíaca de ratos. Para tanto, 48 ratos Wistar, com 60 dias de idade, foram aleatoriamente distribuídos em 6 grupos(N=8/grupo): controle, não treinado (C), treinado, sem administração de droga (T), digoxina sem treinamento (DIGO), verapamil sem treinamento (VERA), treinado, com administração de digoxina (TDIGO) e treinado, com administração de verapamil (TVERA). A digoxina e o verapamil foram administrados via gavagem, na dose de 30μg/kg/dia e 5,0 mg/kg/dia respectivamente, durante todo o período experimental. Os grupos T, TDIGO e TVERA foram submetidos a um programa de TFI em esteira rolante durante 60 dias. Foi aplicado o teste de esforço progressivo máximo (TEM) e determinada a concentração sérica de lactato (LAC) sanguíneo. O TFI consistiu de sessões de corrida em esteira rolante 1 h/dia, 5 dias/semana por 60 dias. A intensidade de treino foi 80% da velocidade máxima (Vmáx) atingida no teste de esforço antes do TFI por 8 min e 20% da Vmáx por 2 min. A função cardíaca foi avaliada por ecocardiograma. Foi coletado o músculo esquelético, o músculo cardíaco e a gordura corporal total (GOR) para os dados anatômicos, o ventrículo esquerdo (VE) para análise histológica e o sangue para a análise bioquímica. A comparação entre os grupos foi realizada por meio da análise de variância (ANOVA) e Kruskal Wallis para o esquema de dois fatores independentes, complementada com o teste de Bonferroni, Tukey ou Dunn. O índice de significância considerado foi de 5%. A relação VE/peso corporal final (PCF), o diâmetro diastólico do VE (DDVE) e diâmetro sistólico do VE (DSVE) foram maiores no grupo TDIGO do que o grupo T e DIGO. Os parâmetros do TEM foram maiores e a concentração de LAC foi menor em ratos treinados em relação aos não treinados. A relação GOR/PCF foi menor no TDIGO e TVERA em relação ao DIGO e VERA, respectivamente. A relação VE/PCF foi maior no TVERA em relação ao VERA. O diâmetro interno do VE (DIVE) do grupo T, TDIGO e TVERA foram maiores em relação ao C, o TDIGO teve aumento em relação ao DIGO. O colesterol total e o LDL foram maiores no TDIGO comparado ao DIGO. A área do cardiomiócito foi maior nos grupos VERA e T comparados ao grupo C. Conclusão: O Treinamento intervalado promoveu hipertrofia cardíaca do tipo excêntrica. Entretanto, a administração concomitante de digoxina ou de verapamil não afetaram a morfologia cardíaca, a função cardíaca e o desempenho físico em ratos submetidos ao treinamento.
The aim of this study was to investigate the effects of chronic administration of cardiotonic (digoxin) and the calcium channel blocker (verapamil) during high-intensity interval exercise training (IET) on physical performance, functional capacity and cardiac morphology of rats. For this study, 48 Wistar rats, 60 days old, were randomly distributed into 6 groups (N = 8 / group): control, untrained (C), trained without drug administration (T), digoxin untrained (DIGO), verapamil without training (VERA), trained with digoxin administration (TDIGO) and trained with verapamil administration (TVERA). Digoxin and verapamil were administered by gavage at a dose of 30μg/kg/day and 5.0 mg.kg-1, respectively, throughout the experimental period. The groups T, TDIGO and TVERA underwent a IET program on a treadmill for 60 days. The progressive maximal exercise test was applied (TPM) and determined the serum concentration of lactate (LAC) blood. The IET consisted of sessions running on a treadmill 1 h/day, 5 days/week for 60 days. The training intensity was 80% of the maximum velocity (Vmax) achieved in the stress test before the TAI for 8 min and 20% of Vmax for 2 min. Cardiac function was assessed by echocardiography. Was collected skeletal muscle, cardiac muscle and total body fat (TBF) for anatomical data, the left ventricle (LV) for histological analysis and blood for biochemical analysis. The comparison between groups was performed using analysis of variance (ANOVA) or Kruskal Wallis for the two independent factors, complemented by the Bonferroni test, Tukey or Dunn. The significance level considered was 5%. The ratio VE final body weight (FBW), LV diastolic diameter (LVDD) and LV systolic diameter (LVSD) were higher in TDIGO group than the group T and DIGO. The parameters MET were higher and the concentration of LAC was lower in rats training in relation to the untrained. The relationship GOR/FBW was lower in TDIGO and TVERA compared to DIGO and VERA respectively. The ratio VE/FBW was higher in TVERA compared to VERA. The of the LV inside diameter (LVID) T group, TDIGO and TVERA were higher compared to C, TDIGO had increased compared to DIGO. Total cholesterol and LDL were higher in TDIGO compared to DIGO. The area of cardiomyocytes was higher in VERA and T compared to group C. Conclusion: TAI induced cardiac hypertrophy of the eccentric type. However, concomitant administration of digoxin or verapamil did not affect the cardiac morphology, cardiac function and physical performance in rats submitted to training.

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Nguyen, Khoa Thuy Diem. "Energy metabolism in the brain and rapid distribution of glutamate transporter GLAST in astrocytes." Thesis, The University of Sydney, 2008. http://hdl.handle.net/2123/3996.

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Glutamate transporters play a role in removing extracellular excitatory neurotransmitter, L-glutamate into the cells. The rate of the uptake depends on the density of the transporters at the membrane. Some studies claimed that glutamate transporters could transit between the cytoplasm and the membrane on a time-scale of minutes. The present study examined the distribution of glutamate transporter GLAST predominantly expressed in rat cortical cultured astrocytes between the membrane and the cytoplasm by using deconvolution microscopy and then analyzing the images. The regulation of the distribution of GLAST was studied in the presence of glutamate transporter substrate (D-aspartate), purinergic receptor activators (α,β-methylene ATP, adenosine), neuroleptic drugs (clozapine, haloperidol), ammonia (hyperammonia) and Na+/K+-ATPase inhibitors (ouabain, digoxin and FCCP). It was demonstrated that the translocation of GLAST towards the plasma membrane was induced by D-aspartate, α,β-methylene ATP, adenosine, clozapine and ammonia (at 100 μM and very high concentrations of 10 mM). However, the inhibition of Na+/K+-ATPase activity had an opposite effect, resulting in redistribution of GLAST away from the membrane. It has previously been claimed that the membrane-cytoplasm trafficking of GLAST was regulated by phosphorylation catalysed by protein kinase C delta (PKC-delta). Involvement of this mechanism has, however, been put to doubt when rottlerin, a PKC-delta inhibitor, used to test the hypothesis showed to inhibit Na+/K+-ATPase-mediated uptake of Rb+, suggesting that rottlerin influenced the activity of Na+/K+-ATPase. As Na+/K+-ATPase converts ATP to energy and pumps Na+, K+ ions, thus helping to maintain normal electrochemical and ionic gradients across the cell membrane. Its inhibition also reduced D-aspartate transport and could impact on the cytoplasm-to-membrane traffic of GLAST molecules. Furthermore, rottlerin decreased the activity of Na+/K+-ATPase by acting as a mitochondrial inhibitor. The present study has focused on the inhibition of Na+/K+-ATPase activity by rottlerin, ouabain and digoxin in homogenates prepared from rat kidney and cultured astrocytes. The activity of Na+/K+-ATPase was measured by the absorption of inorganic phosphate product generated from the hydrolysis of ATP and the fluorescent transition of the dye RH421 induced by the movement of Na+/K+-ATPase. This approach has a potential to test whether the rottlerin effect on Na+/K+-ATPase is a direct inhibition of the enzyme activity. Rottlerin has been found to block the activity of Na+/K+-ATPase in a dose-dependent manner in both rat kidney and astrocyte homogenates. Therefore, rottlerin inhibited the activity of Na+/K+-ATPase directly in a cell-free preparation, thus strongly indicating that the effect was direct on the enzyme. In parallel experiments, ouabain and digoxin produced similar inhibitions of Na+/K+-ATPase activity in rat kidney while digoxin blocked the activity of Na+/K+-ATPase to a greater extent than ouabain in rat cortical cultured astrocytes. In a separate set of experiments, Na+/K+-ATPase in the astrocytic membrane was found to be unsaturated in E1(Na+)3 conformation in the presence of Na+ ions and this could explain the differences between the effects of digoxin and ouabain on the activity of Na+/K+-ATPase in rat astrocytes. In addition, it was found that at low concentrations of rottlerin, the activity of Na+/K+-ATPase was increased rather than inhibited. This effect was further investigated by studying rottlerin interactions with membrane lipids. The activity of Na+/K+-ATPase has been reported to be regulated by membrane lipids. The enzyme activity can be enhanced by increasing fluidity of the lipid membrane. I have, therefore, proposed that rottlerin binds to the membrane lipids and the effects of rottlerin on Na+/K+-ATPase are mediated by changes in the properties (fluidity) of the membrane. The hypothesis was tested by comparing rottlerin and a detergent, DOC (sodium deoxycholate), for their binding to the lipids by using a DMPC (1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine) monolayer technique. DOC has been shown to both increase and inhibit activity of Na+/K+-ATPase in a manner similar to that displayed by rottlerin. The effects of rottlerin and DOC on the DMPC monolayers were studied by measuring the surface pressure of DMPC monolayers and surface area per DMPC molecule. I established that both rottlerin and DOC decreased the surface pressure of DMPC monolayers and increased the surface area per DMPC molecule. This indicates that both rottlerin and DOC penetrated into the DMPC monolayers. If rottlerin can interact with the lipids, changes in fluidity of the lipid membrane cannot be ruled out and should be considered as a possible factor contributing to the effects of rottlerin on the activity of Na+/K+-ATPase. Overall, the study demonstrates that rottlerin is not only a PKC-delta inhibitor but can have additional effects, both on the enzyme activities (Na+/K+-ATPase) and/or on lipid-containing biological structures such as membranes. The findings have implication not only for studies where rottlerin was used as a supposedly specific PKC-delta inhibitor but also for mechanisms of its toxicity.

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Nguyen, Khoa Thuy Diem. "Energy metabolism in the brain and rapid distribution of glutamate transporter GLAST in astrocytes." University of Sydney, 2008. http://hdl.handle.net/2123/3996.

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Doctor of Philosophy (Medicine)
Glutamate transporters play a role in removing extracellular excitatory neurotransmitter, L-glutamate into the cells. The rate of the uptake depends on the density of the transporters at the membrane. Some studies claimed that glutamate transporters could transit between the cytoplasm and the membrane on a time-scale of minutes. The present study examined the distribution of glutamate transporter GLAST predominantly expressed in rat cortical cultured astrocytes between the membrane and the cytoplasm by using deconvolution microscopy and then analyzing the images. The regulation of the distribution of GLAST was studied in the presence of glutamate transporter substrate (D-aspartate), purinergic receptor activators (α,β-methylene ATP, adenosine), neuroleptic drugs (clozapine, haloperidol), ammonia (hyperammonia) and Na+/K+-ATPase inhibitors (ouabain, digoxin and FCCP). It was demonstrated that the translocation of GLAST towards the plasma membrane was induced by D-aspartate, α,β-methylene ATP, adenosine, clozapine and ammonia (at 100 μM and very high concentrations of 10 mM). However, the inhibition of Na+/K+-ATPase activity had an opposite effect, resulting in redistribution of GLAST away from the membrane. It has previously been claimed that the membrane-cytoplasm trafficking of GLAST was regulated by phosphorylation catalysed by protein kinase C delta (PKC-delta). Involvement of this mechanism has, however, been put to doubt when rottlerin, a PKC-delta inhibitor, used to test the hypothesis showed to inhibit Na+/K+-ATPase-mediated uptake of Rb+, suggesting that rottlerin influenced the activity of Na+/K+-ATPase. As Na+/K+-ATPase converts ATP to energy and pumps Na+, K+ ions, thus helping to maintain normal electrochemical and ionic gradients across the cell membrane. Its inhibition also reduced D-aspartate transport and could impact on the cytoplasm-to-membrane traffic of GLAST molecules. Furthermore, rottlerin decreased the activity of Na+/K+-ATPase by acting as a mitochondrial inhibitor. The present study has focused on the inhibition of Na+/K+-ATPase activity by rottlerin, ouabain and digoxin in homogenates prepared from rat kidney and cultured astrocytes. The activity of Na+/K+-ATPase was measured by the absorption of inorganic phosphate product generated from the hydrolysis of ATP and the fluorescent transition of the dye RH421 induced by the movement of Na+/K+-ATPase. This approach has a potential to test whether the rottlerin effect on Na+/K+-ATPase is a direct inhibition of the enzyme activity. Rottlerin has been found to block the activity of Na+/K+-ATPase in a dose-dependent manner in both rat kidney and astrocyte homogenates. Therefore, rottlerin inhibited the activity of Na+/K+-ATPase directly in a cell-free preparation, thus strongly indicating that the effect was direct on the enzyme. In parallel experiments, ouabain and digoxin produced similar inhibitions of Na+/K+-ATPase activity in rat kidney while digoxin blocked the activity of Na+/K+-ATPase to a greater extent than ouabain in rat cortical cultured astrocytes. In a separate set of experiments, Na+/K+-ATPase in the astrocytic membrane was found to be unsaturated in E1(Na+)3 conformation in the presence of Na+ ions and this could explain the differences between the effects of digoxin and ouabain on the activity of Na+/K+-ATPase in rat astrocytes. In addition, it was found that at low concentrations of rottlerin, the activity of Na+/K+-ATPase was increased rather than inhibited. This effect was further investigated by studying rottlerin interactions with membrane lipids. The activity of Na+/K+-ATPase has been reported to be regulated by membrane lipids. The enzyme activity can be enhanced by increasing fluidity of the lipid membrane. I have, therefore, proposed that rottlerin binds to the membrane lipids and the effects of rottlerin on Na+/K+-ATPase are mediated by changes in the properties (fluidity) of the membrane. The hypothesis was tested by comparing rottlerin and a detergent, DOC (sodium deoxycholate), for their binding to the lipids by using a DMPC (1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine) monolayer technique. DOC has been shown to both increase and inhibit activity of Na+/K+-ATPase in a manner similar to that displayed by rottlerin. The effects of rottlerin and DOC on the DMPC monolayers were studied by measuring the surface pressure of DMPC monolayers and surface area per DMPC molecule. I established that both rottlerin and DOC decreased the surface pressure of DMPC monolayers and increased the surface area per DMPC molecule. This indicates that both rottlerin and DOC penetrated into the DMPC monolayers. If rottlerin can interact with the lipids, changes in fluidity of the lipid membrane cannot be ruled out and should be considered as a possible factor contributing to the effects of rottlerin on the activity of Na+/K+-ATPase. Overall, the study demonstrates that rottlerin is not only a PKC-delta inhibitor but can have additional effects, both on the enzyme activities (Na+/K+-ATPase) and/or on lipid-containing biological structures such as membranes. The findings have implication not only for studies where rottlerin was used as a supposedly specific PKC-delta inhibitor but also for mechanisms of its toxicity.

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Howard, Cory M. "Characterization of the CXCR4-LASP1-eIF4F Axis in Triple-Negative Breast Cancer." University of Toledo Health Science Campus / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=mco1596298549051863.

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25

Abarca, Jacob. "The effect of beta-blocker therapy, ACE inhibitor therapy,and digoxin therapy on the risk of hospitalization and resource utilizationamong patients with congestive heart failure enrolled in a managed care organization." Thesis, The University of Arizona, 2001. http://hdl.handle.net/10150/291440.

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Congestive heart failure (CHF) represents the end-stage of all heart disease. The current incidence of CHF in the US is 550,000 cases per year and is expected to increase in the future. Therapy with β-blockers, ACE inhibitors, and digoxin has been associated with a decreased risk of all-cause hospitalization and CHF-related hospitalization in randomized clinical trials. The purpose of this study was to evaluate the effect of beta-blocker, ACE inhibitor, and digoxin therapy on these outcomes and total direct medical costs among patients with CHF enrolled in a managed care plan. Neither therapies were associated with a statistically significant reduction in CHF-related hospitalizations. ACE inhibitor therapy (180 days) was associated with a significant decrease (34.7 percent, p < 0.0001) in the risk of all-cause hospitalization and lower total direct medical costs ($2135, p < 0.001) over a one year period. The results suggest increased use of ACE inhibitors is warranted.

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26

Duan, Qiming. "Cardiac Na/K-ATPase in Ischemia-Reperfusion Injury and Cardioprotection." University of Toledo Health Science Campus / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=mco1388151402.

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ALEMANNI, MATTEO. "The modulation of SERCA pump activity as a tool for management of hearth failure." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2009. http://hdl.handle.net/10281/7462.

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The current positive inotropic interventions for the management of heart failure (HF) are all associated to an unchanged or increased long term mortality, which limit their use. Istaroxime (IST) is a novel positive inotrope able to inhibit Na+, K+ ATPase and to stimulate SERCA pump. We employed IST as a tool to assess the role of a mild SERCA stimulation as a positive inotropic intervention. In a guinea pig model of HF, where the sarcoplasmic reticulum (SR) function was deranged, IST was able to restore an optimal SR function, increase the SR Ca2+ content and to improve all the EC coupling parameters considered. The comparison if IST and digoxin, a pure inhibitor of Na+, K+ ATPase, in mouse ventricular myocytes, showed that IST was less pro-arrhythmic than digoxin, as already observed in guinea pig. Digoxin induced a rapid accumulation of cytosolic Ca2+, while IST did not, and neither compound directly affected SR Ca2+ leakage, suggesting that a better compartmentalization of the ion was achieved in the presence of IST by the stimulation of SERCA pump. We concluded that the mild stimulation of SERCA is associated to a reduced pro-arrhythmic effect, and that it might represent a promising target for a new class of positive inotropic interventions associated to a reduced long term mortality.

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Claassen, Marleen. "Exploring the contribution of prenatal stress to the pathogenesis of autism as a neurobiological developmental disorder : a dizygotic twin study." Diss., University of Pretoria, 2006. http://hdl.handle.net/2263/23190.

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This research project explores the contribution of prenatal stress to the pathogenesis of autism as a neurobiological developmental disorder. The neurobiological impact of stress prior to the 28th week of gestation might produce structural neural changes, specifically regarding the cerebellum, the brain stem and limbic pathways, including the hippocampal area, which concept relates closely to the pathogenesis of autism. In this research project a significant focus is placed on prenatal hipothalamic-pituary-adrenal (HPA) activity due to the HPA axis’ interactivity with cortisol, digoxin and serotonin, as these biochemicals are significantly implicated in programmed foetal development, postnatal cortical behaviour, postnatal learning, as well as in functional impairment of socialization, communication and imagery associated with autism. Based upon the rationale of this research project and the conceptualisation of the topic of interest, the research problem was formulated as follows: In what unique ways does prenatal stress contribute to the pathogenesis of autism as a neurobiological developmental disorder? Sub questions included: Did the mother of the dizygotic twins experience significant stress during the period of gestation? What structural brain differences can be observed among the dizygotic twins at hand of MR-imaging? To which periods of prenatal development can these structural differences be related? How do these differences account for sensory, motor, cognitive, and affective behavioural differences among the dizygotic twins? What plasma differences can be observed among the dizygotic twins at hand of blood sampling? How does elevation of pre- and postnatal glucocorticoids relate to plasma difference among the dizygotic twins? How do these plasma differences account for sensory, motor, cognitive, and affective behavioural differences among the dizygotic twins? This research project represents quantitative research. The mode of inquiry is non-experimental at hand of a single dizygotic twin study. The following data generating strategies were employed: clinical intake interviews, administration of a diagnostic stress inventory and the 16-PF Questionnaire, MR-imaging, and the collection of blood plasma pathology results.
Dissertation (M.Ed)--University of Pretoria, 2006.
Educational Psychology
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Weitkamp, Christine [Verfasser]. "Warum zeigen die Herzglykoside Ouabain und Digoxin unterschiedliche Kreislaufwirkung? : Charakterisierung eines mutmaßlichen Herzglykosid-Bindungsproteins im Serum und Analyse der Wirkung beider Steroide auf die Endothelin-1- und NO-Freisetzung aus arteriellen Endothelzellen / Christine Weitkamp." Wettenberg : VVB Laufersweiler, 2005. http://d-nb.info/976405792/34.

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30

HANOT, REGIS. "Tolerance de l'association digoxine - cibenzoline : impact des antiarythmiques sur le traitement par digoxine." Lille 2, 1993. http://www.theses.fr/1993LIL2M037.

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Moriau, Didier. "Aspects pharmacocinétiques de l'interaction digoxine-quinidine/." Paris 5, 1989. http://www.theses.fr/1989PA05P010.

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32

Boe͏̈l, Frédéric. "Automatisation du prélèvement et du dosage HPLC de l'essai de dissolution des comprimés de digoxine." Paris 5, 1994. http://www.theses.fr/1994PA05P189.

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33

MOLINARI, BENOIT PATRICIA. "La digoxine chez le sujet age : interet du dosage de la digoxinemie ; application pratique." Toulouse 3, 1992. http://www.theses.fr/1992TOU31089.

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CANO, CANO NATHALIE. "Evaluation de l'immunoreactivite d'anticorps anti-digoxine en immunotoxicotherapie." Paris 6, 1993. http://www.theses.fr/1993PA066706.

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L'immunotoxicotherapie repose sur l'administration d'anticorps ou de fragments specifiques d'un toxique. L'objectif de notre etude a ete d'evaluer l'influence des caracteristiques d'un anticorps (affinite et dose) sur son potentiel de detoxication. Nous avons compare l'activite de 3 anticorps monoclonaux anti-digoxine, d'affinites differentes, a l'aide de modeles in vitro et in vivo. In vitro, la dissociation de la digoxine de son recepteur en presence d'anticorps est d'autant plus elevee que l'affinite de l'anticorps est grande. De plus, pour un anticorps donne, la dissociation est fonction de la concentration d'anticorps dans le millieu n reactionnel. La restauration de l'activite du recepteur na, k, atpase est maximale pour un rapport anti corps-digoxine stoechiometrique. In vivo, sur un modele de redistribution plasmatique de la digoxine chez le rat, l'administration des anticorps provoque une augmentation des concentrations plasmatiques de digoxine totale (redistribution) et une diminution de la fraction libre de digoxine (sequestration) d'autant plus importantes que l'affinite est grande. A une dose 5 fois superieure a la molarite, alors que l'anticorps de forte affinite a atteint son efficite maximale, l'igg d'affinite intermediaire possede une efficacite de redistribution comparable a celle de l'anticorps de forte affinite. Il existe une relation signoidale entre les parametres de redistribution, la dose et l'affinite qui permet de maitriser la dose detoxifiante en fonction de l'affinite et du nombre de sites actifs administres. Nos resultats indiquent une bonne correlation entre les etudes in vitro et in vivo

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Pignotti, René-Pierre. "Digoxine et fonction ventriculaire gauche de la personne agee." Bordeaux 2, 1988. http://www.theses.fr/1988BOR25288.

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36

Oweis, Shadi. "Cardiotonic Steroids Down-Regulate Sodium Hydrogen Exchanger Expression in the Proximal Tubule Cells." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1278521957.

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CLADET, PHILIPPE. "Digoxine - digitaline : le choix du traitement face au risque de surdosage chez la personne agee : a propos de 46 observations." Lille 2, 1990. http://www.theses.fr/1990LIL2M029.

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DAMASE, LUC. "Recherches pharmacologiques sur le mecanisme d'interaction digoxine amiodarone chez l'homme." Toulouse 3, 1988. http://www.theses.fr/1988TOU31164.

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39

Wahyono, Djoko. "Production et caractérisation d'anticorps monoclonaux dirigés contre la digoxine. Intérêt en immunoanalyse." Montpellier 1, 1990. http://www.theses.fr/1990MON13507.

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LAURANT, ERIC. "Intoxication grave au laurier rose : a propos d'un cas traite par les anticorps anti-digoxine." Clermont-Ferrand 1, 1991. http://www.theses.fr/1991CLF13061.

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41

Guedeney, Xavier. "Contribution à l'étude des composés digitaliques endogènes : propriétés immunologiques et biochimiques en période périnatale." Paris 5, 1988. http://www.theses.fr/1988PA05P614.

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BESSON, LAVEDAN SYLVIE. "Etude de la prescription de digoxine et de ses dosages seriques dans trente services du c. H. U. Purpan (toulouse) pendant deux ans." Toulouse 3, 1991. http://www.theses.fr/1991TOU31050.

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43

Marcaggi, P. "Intoxications digitaliques aigues : conduite a tenir en urgence ; interet de l'antidote anti-digoxine." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20052.

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44

Commeau, Philippe. "Etude des variations de la pharmacocinétique et des effets pharmacodynamiques cardiovasculaires de la Digoxine sous l'influence de la coadministration de la Nicardipine chez l'homme en insuffisance cardiaque." Rouen, 1986. http://www.theses.fr/1986ROUE05NR.

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L'effet des inhibiteurs du canal calcique lent sur les taux sériques de digoxine a largement été étudié. Ces travaux ont principalement porté sur le vérapamil et la nifépipine Ces inhibiteurs calciques augmentent de façon significative les concentration,. Sériques de la digoxine , principalement par une réduction de la clearance totale de la digoxine. Par contre l'association nicardipine-digoxine a été beaucoup plus rarement étudiée. Le but de cette étude a été double i -apprécier l'influence de la nicardipine orale sur la pharmacocinétique de la digoxine -apprécier les variations éventuelles des effets pharmacodgnamiques de la digaxine chez 9 patients atteints d' insuffisance cardiaque chronique congestive. L'étude pharmacodynemique a été réalisée grâce à l'emploi de 3 méthodes : échocardiographie uni- et bi-dimensionnelle , intervalles de temps systolique et cathéterisme cardiaque. L'administration de nicardipine per os chez ces sujets traités de façon chronique par la digoxine : -semble modifier peu la pharmacocinétique de la digoxine et de toute façon jamais dons les zones toxiques. L'interprétation des variations des taux sériques de digoxine est complexe. -améliore la fonction ventriculaire gauche et la contractilité myocardique grâce à une réduction de la post-charge due à une vasodilatation périphérique liée à l'action de la nicardipine, tendant à contrebalancer la vasoconstriction induite par la digoxine.

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POULAIN, GELARD YVETTE. "Traitement des intoxications digitaliques massives par les anticorps anti-digoxine fractionnes (fab) : a propos d'un cas, revue de la litterature." Nantes, 1989. http://www.theses.fr/1989NANT005M.

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46

Navarro-Teulon, Isabelle. "Ingénierie génétique des immunoglobulines appliquée au diagnostic et à l'immunoanalyse : mise au point d'un nouvel immunodosage de Digoxine, construction de banques combinatoires de fragments d'anticorps anti-thyroglobuline." Montpellier 1, 1995. http://www.theses.fr/1995MON13508.

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47

Salphati, Laurent. "P-glycoproteine et cytochrome p450 3a : interactions potentielles et roles complementaires dans l'absorption et la disposition des drogues." Paris 11, 1998. http://www.theses.fr/1998PA114805.

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48

Mundet, i. Tudurí Xavier. "Estudi de la utilització de la digoxina. Utilitat de la digoxinèmia com a marcador del seu ús." Doctoral thesis, Universitat Autònoma de Barcelona, 1990. http://hdl.handle.net/10803/5401.

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49

Lacarelle, Bruno. "Contribution de la pharmacocinetique a la maitrise et a l'elucidation des origines de la variabilite de la reponse therapeutique : applications aux aminosides et a la digoxine." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX22963.

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50

Reibel, Monique. "Le dosage des digitaliques chez l'hemodialyse : pharmacocinetique de la digitoxine, presence d'une activite digitalis-like endogene." Strasbourg 1, 1988. http://www.theses.fr/1988STR1M058.

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Dissertations / Theses on the topic 'Digoxin'

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