Дисертації з теми "Thyroid hormones Therapeutic use"
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Veltri, Flora. "Variables influencing thyroid function during pregnancy and their potential use in clinical practice." Doctoral thesis, Universite Libre de Bruxelles, 2020. https://dipot.ulb.ac.be/dspace/bitstream/2013/313347/4/TDM.pdf.
Повний текст джерелаDoctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
伍伯堯 and Pak-yiu Ng. "Investigation on the differential expression and hormonal regulation of olfactomedin in uterus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557765.
Повний текст джерелаRoberts, April M. "Steroid hormone treatments alter growth characteristics in transformed human ovarian cell lines." Virtual Press, 2003. http://liblink.bsu.edu/uhtbin/catkey/1265095.
Повний текст джерелаMugari, Mufaro Buhlebenkosi. "The inhibitory effect of rooibos on cytochromes P450 and downstream in vitro modulation of steroid hormones." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96680.
Повний текст джерелаENGLISH ABSTRACT: This study describes: 1. Substrate binding assays investigating the effects of methanolic extracts of unfermented and fermented Rooibos on the binding of natural substrates to ovine adrenal microsomal and mitochondrial P450 enzymes, demonstrating the interference of substrate binding in the presence of the Rooibos extracts. 2. The effects of selected flavonoids (quercetin, rutin and aspalathin) on the binding of natural substrates to ovine adrenal microsomal and mitochondrial P450 enzymes, demonstrating interference of substrate binding in the presence of the flavonoid compounds. 3. Substrate conversion assays in non-steroidogenic COS-1 cells to investigate the effects of methanolic extracts of unfermented and fermented Rooibos on the activity of key steroidogenic P450 enzymes (CYP17A1, CYP21A2, CYP11B1, and CYP11B2), demonstrating inhibition of the catalytic activity in the presence of Rooibos extracts. 4. The effects of selected flavonoids on the substrate conversion of the aforementioned key steroidogenic enzymes expressed in COS-1 cells. 5. An investigation of the effect of methanolic extracts of unfermented and fermented Rooibos on steroid hormone production in human adrenal H295R cells under basal and stimulated conditions, demonstrating the modulating effects of unfermented and fermented Rooibos extracts. Basal and stimulated steroid hormone production was decreased in the presence of unfermented and fermented Rooibos.
AFRIKAANSE OPSOMMING: Hierdie studie beskryf: 1. Die gebruik van substraatbindings-essais om die effek van metanoliese ekstrakte, van gefermenteerde- en ongefermenteerde Rooibos, op die binding van die natuurlike substrate aan skaap adrenale mikrosomale en -mitochondriale P450 ensieme te bepaal. Daar is getoon dat die ekstrakte 'n beduidende inhiberende effek op ensiemsubstraatinteraksie gehad het. 2. Die die inhiberende effek van geselekteerde flavonoïede (kwersetien, rutien and aspalatien) op die binding van die natuurlike substrate aan skaap adrenale mikrosomale en -mitochondriale P450 ensieme. 3. Die gebruik van substraatomsettings-essais in nie-steroïedogeniese COS-1 selle, om die effek van gefermenteerde- en ongefermenteerde Rooibos ekstrakte op die aktiwiteit van die steroïedogeniese P450 ensieme (CYP17A1, CYP21A2, CYP11B1, and CYP11B2) se katalitiese aktiwiteit te bepaal. Daar kon aangetoon word dat die katalitise aktiwiteite van bg. ensieme beduidend beïnvloed word deur die Rooibos ekstrakte. 4. Die gebruik van substraatomsettings-essais in nie-steroïedogeniese COS-1 selle, om die effek van geselekteerde flavonoïede op die aktiwiteit van bogenoemde steroïedogeniese P450 ensieme te bepaal. 5. 'n Ondersoek na die invloed van metanoliese ekstrakte van gefermenteerde- en ongefermenteerde Rooibos op steroïedhormoon biosintese in die menslike adrenale H295R-selmodel. Die ondersoek, onder basale en gestimuleerde toestande, het getoon dat beide Rooibosekstrakte in bogenoemde toestande steroïedhormoon produksie geinhibeer het.
Meyer, Eric. "Comparative bioavailability and ranking of topical corticosteroid formulations." Thesis, Rhodes University, 1985. http://hdl.handle.net/10962/d1001471.
Повний текст джерела林穎華 and Wing-wah Phoebe Lam. "A systematic review of postoperative treatments for laser eye surgery." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970643.
Повний текст джерелаMagnus, Ashley Denis. "Aspects of the bioavailability of topical corticosteroid formulations." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1009516.
Повний текст джерелаKMBT_363
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Milliken, Erin L. "USE OF A TRANSGENIC MOUSE MODEL OF OVARIAN HYPERSTIUMLUATION TO IDENTIFY THERAPEUTIC TARGETS AND MECHANISMS IN HORMONE-INDUCED MAMMARY CANCER." Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1121273034.
Повний текст джерелаSalb, Nicole [Verfasser], та Peter [Akademischer Betreuer] Nelson. "Application of engineered mesenchymal stem cells as therapeutic vehicles for the treatment of solid tumors : HIF1α-based targeting and the influence of thyroid hormones / Nicole Salb ; Betreuer: Peter Nelson". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1171131372/34.
Повний текст джерелаHorn, Je'nine. "The analysis of 6- and 24-hour iodine-131 thyroid uptake in patients with Graves' disease at Universitas Hospital." Thesis, [Bloemfontein?] : Central University of Technology, Free State, 2007. http://hdl.handle.net/11462/102.
Повний текст джерелаIn the South African Health Services (SAHS) it is each health worker’s responsibility to find ways to reduce health care cost and improve health service to the public. The measurement of radioactive iodine uptake (RAIU) by the thyroid gland for diagnostic purposes has been used as early as the 1940s. The 24-hour (hr) iodine-131 (131I) uptake measurement is traditionally used for the calculation of the 131I administered activity for therapy dosage. This entails that the patient’s hospitalisation is prolonged, which increases the costs. The literature also indicates that the 24-hr 131I uptake value can be discarded and only the 6-hr 131I uptake measurement is needed to calculate administered activity for therapeutic dosages for Graves’ patients. Therefore, if it can be confirmed that the 6-hr 131I uptake measurement alone is needed, the SAHS could decrease hospitalisation costs. The overall goal of the investigation was to analyse the 6-hr and 24-hr 131I uptake measurements of patients with Graves’ disease at the Universitas Hospital. The aim was to determine the relationship between the 6-hr and 24- hr RAIU values to establish the therapeutic dosage for Graves’ disease. To achieve the aim, three objectives were set. First, to serve as a background to the investigation, a literature survey relating to the RAIU measurements of patients with Graves’ disease was made. Second, a retrospective analysis was performed by collecting the 6-hr and 24-hr 131I uptake measurements of patients with proven Graves’ disease at the Universitas Nuclear Medicine Department (UNMD). Finally, the data obtained from the retrospective analysis was analysed, summarised and compared to answer the investigation questions. The investigation group included patients with confirmed Graves’ disease who had undergone both the 6- and 24-hr 131I RAIU at the Universitas Hospital from the beginning of 2004 to the end of 2005. Graves’ disease is confirmed by the following factors at the UNMD, namely: Suppressed TSH, elevated T4 and T3 values, an increased uptake on the 99mTc-pertechnetate scan and increased 6- and 24-hr 131I RAIU values. The UNMD statistics show that 178 patients were diagnosed with Graves’ disease during this period. The patients of the investigation group included both male and female patients from different races, ranging from 15-75 years. In order to increase the validity of the investigation, all factors that could influence the accuracy of the 131I thyroid uptake test were excluded. After the exclusion and inclusion criteria had been applied, the final investigation group was made up of 124 Graves’ disease patients. The data obtained from the patient files was noted on the different data sheets (see Appendix A) for further analysis. The information from these data sheets was then used to obtain the investigation results. The Department of Biostatistics of the University of the Free State (UFS) was consulted for recommendations regarding the management of data and the processing of results. All values were summarised by means and Standard Deviations (SD) or percentiles. Mean or median differences were calculated with a 95% Confidence Interval (CI). A regression analysis was made between the 6-hr and 24-hr 131I RAIU values. The highest RAIU value is the best to calculate the therapeutic dosage, as this gives a true reflection of the thyroid function of a Graves’ disease patient. In the investigation group the median of the 24-hr 131I RAIU values was higher than the 6-hr 131I RAIU values. The findings showed that the 24-hr 131I RAIU in most of the investigation group was the highest value and most effective to calculate the 131I therapeutic dosage. At a time when research-based practice is taking on an increasingly important role, it is essential for nuclear medicine departments to make evidence-based recommendations. This investigation found that the correlation between the 6-hr and 24-hr RAIU clearly justified the cost spent on Graves’ disease patients who must stay overnight for the 24-hr 131I RAIU procedure.
Schloms, Lindie. "The inhibition of adrenal steroidogenic enzymes and modulation of glucocorticoid levels in vitro and in vivo by aspalathus linearis (rooibos)." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97000.
Повний текст джерелаENGLISH ABSTRACT: This study describes: • the influence of a methanolic extract of unfermented Rooibos and five major Rooibos flavonoids, aspalathin, nothofagin, rutin, orientin and vitexin, on the activities of key adrenal steroidogenic enzymes - cytochrome P450 17β- hydroxylase/17,20-lyase (CYP17A1), 3β-hydroxysteroid dehydrogenase • the development of a novel UPLC-MS/MS method for the separation and quantification of 21 adrenal steroid metabolites; • the influence of Rooibos and aforementioned flavonoids on adrenal steroid hormone production in H295R cells - a human adrenal carcinoma cell line expressing the enzymes catalysing the production of mineralocorticoids, glucocorticoids and adrenal androgens, assayed under both basal (normal) and forskolin-stimulated (stressed) conditions; • the influence of Rooibos on the inter-conversion between cortisol and cortisone by 11βHSD1 and 11βHSD2 expressed in CHO-K1 cells; • the influence of Rooibos consumption on circulating steroid hormone levels and ratios in male Wistar rats; • the influence of Rooibos consumption on circulating steroid hormone levels and ratios in male and female human test subjects at risk for developing cardiovascular disease. (3βHSD2), cytochrome P450 21-hydroxylase (CYP21A2) and cytochrome P450 11β-hydroxylase (CYP11B1), expressed in non-steroidogenic COS-1 cells;
AFRIKAANSE OPSOMMING: Hierdie studie beskryf: • die invloed van metanoliese ekstrakte van ongefermenteerde Rooibos en vyf van die hoof flavonoïedverbindings in Rooibos, aspalatien, notofagien, rutien, oriëntien en viteksien, op die aktiwiteite van ensieme wat steroïedbiosintese in die bynier kataliseer – sitochroom P450 17α-hidroksilase/17,20-liase (CYP17A1), 3β-hidroksisteroïed dehidrogenase (3βHSD2), sitochroom P450 21-hidroksilase (CYP21A2) en sitochroom P450 11β-hidroksilase (CYP11B1), uitgedruk in nie-steroïed produserende COS-1 selle; • die ontwikkeling van ‘n geskikte UPLC-MS/MS metode vir die skeiding en kwantifisering van 21 steroïedmetaboliete in die bynier; • die invloed van Rooibos en die bg. flavonoïede op steroïedproduksie in H295R selle – ‘n menslike bynier kanker sellyn gekenmerk deur die ekspressie van die steroidogeniese ensieme wat die produksie van mineralokortikoïede, glukokortikoïede en bynierandrogene kataliseer, geanaliseer onder beide basale (normale) en forskoliengestimuleerde (gestresde) kondisies; • die invloed van Rooibos op die omeenskakeling tussen kortisol en kortisoon deur 11βHSD1 and 11βHSD2 in CHO-K1 selle; • die invloed van Rooibosinname op vlakke van sirkulerende steroïed hormone en relatiewe verhoudings in die bloed van manlike Wistarrotte; • die invloed van Rooibosinname op sirkulerende steroïed hormoon vlakke en relatiewe verhoudings in die bloed van mans en vrouens met ‘n hoë risiko vir die ontwikkeling van kardiovaskulêre siektes.
Parreira, Samara Lamounier Santana. ""Quantificação da força muscular e habilidades motoras de pacientes com distrofia muscular de Duchenne, em tratamento com corticoterapia"." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-04042006-153416/.
Повний текст джерелаIn 32 patients with Duchenne muscular dystrophy and receiving steroid therapy we assessed muscle strength along a follow-up of 14 months using Medical Research Council scale, Hammersmith functional motor scale, timed testing for rising from the floor and walking 9 meters, as well as rising weights. The tests were repeated monthly along the first 6 months and every two months by the rest of the follow-up. The study revealed a trend to functional stability and that the muscle strength can be evaluated at 3 and 6 months of treatment and then every 6 months while the steroid therapy is maintained
Palvie, Stefanie Michelle. "An investigation into the neuroprotective effects of dehydroepiandrosterone." Thesis, Rhodes University, 2006. http://hdl.handle.net/10962/d1003260.
Повний текст джерелаFernandes, Roberta Possato. "Quantificação do RNAm de tireoglobulina em sangue periférico de pacientes com câncer diferenciado de tireóide: acompanhamento a longo prazo." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-15042009-154717/.
Повний текст джерелаThe differentiated thyroid carcinoma (DTC) encloses 95% of all thyroid malignant disease. In USA, it increased 2,4 times in recent years (1973- 2002). The treatment includes total thyroidectomy, ablation with radioiodine (RAI) followed by TSH suppression with L-Thyroxine. The cancer recurrence occurs in 20% of the cases. Periodic evaluation through imaging examinations and serum thyroglobulin (TG) measurements by imunoassays method is recommended for careful follow-up of these patients. The anti-TG antibodies prevalence is 15-25% and would impair, partially, the serum TG use as a tumor marker. An alternative method to identify the recurrence of the tumor is the thyroid cells detection in peripheral blood, through the TG messenger RNA quantification (mRNA-TG) by real time RT-PCR. This new methodology increases the sensitivity detection for this molecule. The objective of this study was to verify the mRNA-TG peripheral blood quantification significance, as a complementary diagnostic method in the long term follow up of patients with DTC. Fourty five blood samples from patients with DTC have been collected before and 24, 48, 72 hours, 7 days, 1, 3, 6, 9 months, 1, 2, 4, 5, 6 and 7 years after the ablation therapy. Extensive technique standardization for mRNA-TG measurements was carried out to exclude methodological interventions and two housekeeping genes (GAPDH and HPRT1) were used to calculate the mRNA-TG concentrations. Concomitantly, serum TG measurements, hormonal profile and antibodies anti-TG assays were performed. The whole body scan was performed 7 days after RAI ablation to determine the stage of the disease. It was not possible to establish a cut-point value for mRNA-TG. The mRNA-TG did not differentiated the clinical stage of the disease in the long term follow-up and neither in the presence of anti-TG antibodies and TSH30ng/mL. Serum TG was able to differentiate the clinical stage of the patients during the follow-up. In conclusion mRNA-TG is not a good marker for the DCT recurrence, even when technical standardization, long term evaluation and the presence of antibodies anti-TG were considered. Thus it could not be used as a complementary diagnostic method in the DTC patients follow-up. This study confirmed the high sensivity of the real time RT-PCR whereas with very low specificity, consequently is unviable to be used in the DTC patients follow-up
Cotrim, Denise Moreira de Andrade. "Estudo das interleucinas no processo inflamatório na doença pulmonar obstrutiva crônica, Prednisona/uso terapêutico." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5150/tde-09102014-091632/.
Повний текст джерелаAlthough in chronic obstructive lung disease the use of oral corticoid is not indicated in the maintenance treatment, we identified a group of patients that make use of this medication continuously. The objective of this study was to analyze the inflammatory phenomena associated to the attempt of progressive reduction of oral corticoids in these patients. We evaluated induced sputum of 14 patients on long-term use of oral corticoids. After the basal evaluation, accomplished while the patients made use of their habitual dose of the medication (V0), we increased the dose of prednisone to 40 mg daily for two weeks (V1). To proceed we reduced the dose progressively until an exacerbation occurred (EXAC), when the dose of prednisone 40 mg daily was reintroduced for two weeks (AFTER). We compared the results to a group of patients with COPD not on use of oral corticoids, that were appraised in the basal condition (V0), when they exacerbated (EXAC) and after the treatment with prednisone 40 mg daily for two weeks (AFTER). The variables analyzed in the sputum were:, % of neutrophils, % of eosinophils, % of macrophages, total number of cells, interleukins 4, 6 and 8. We verified that the corticoid group presented a significant increase in the percentage of eosinophils at the exacerbation in relation to V0, and a significant reduction in AFTER in relation to EXAC. This didn\'t happen in the non corticoid group. When we compared the two groups we observed that the concentration of the interleukins was significantly higher in corticoid group in V0 and at the exacerbation in relation to the non corticoid group. When we analyzed the behavior of the interleukins along the evaluations in each group we observed that interleukin 4 tended to an elevation at the exacerbation in the corticoid group, without reaching statistical significance. Interleukins 6 and 8 increased significantly in the corticoid group in the visit AFTER. We concluded that the progressive reduction of oral corticoid induces exacerbation in patients with COPD on long-term use of prednisone with an eosinophilic inflammatory process that tends to reverse after the increase of the dose of the corticoid
Vale, Catarina Afonso Couto e. "The role of thyroid hormones in heart failure: triiodothyronine as a therapeutic target in HFpEF." Master's thesis, 2019. https://hdl.handle.net/10216/119942.
Повний текст джерелаVale, Catarina Afonso Couto e. "The role of thyroid hormones in heart failure: triiodothyronine as a therapeutic target in HFpEF." Dissertação, 2019. https://hdl.handle.net/10216/119942.
Повний текст джерела"Apoptotic effects of iodine in thyroid cancer cells." Thesis, 2010. http://library.cuhk.edu.hk/record=b6074822.
Повний текст джерелаThyroid cancer is the most common endocrine malignancy and exhibits the full range of malignant behaviors from the relatively indolent occult differentiated thyroid cancer to uniformly aggressive and lethal anaplastic thyroid cancer. Iodine is a well known key element in thyroid normal function maintenance and thyroid cancer development. However, the mechanisms of iodine in thyroid cancer cells development are limited. Recent researches have indicated that iodine could induce cancer cells apoptosis, staying clear from the dysfunction of iodide-specific transportation systems in thyroid cancer cells. Thus, iodine-induced apoptosis may be an effective pathway for iodine to affect thyroid cancer development, but we know little about them.
To further explore iodine on the apoptotic effects of chemotherapeutic agents in thyroid cancer, anaplastic thyroid cancer cell line ARO was used. Anaplastic thyroid cancer is lethal because of its rapid progression and poor response to chemotherapy and radioiodine therapy. The study examined the effect of moderate dose of iodine (50 muM) on the apoptosis of ARO cells treated with doxorubicin (Dox) and histone deacetylase inhibitor sodium butyrate (NaB). The cytotoxic effect of either Dox or NaB alone was limited, but co-administration of NaB and Dox (NaB-Dox) significantly increased mitochondrial-mediated apoptosis. The effects of iodine to apoptosis-induced by the two agents were diversified. Iodine reduced the apoptosis induced by Dox or NaB-Dox but promoted apoptosis induced by NaB. To explain this diversifying finding, the experiment found that iodine exaggerated NaB-mediated Bcl-xL down-regulation. In contrast, it reduced the effect of Dox on the decrease of Bcl-xL expression. Further experiments showed that iodine regulated the level of Bcl-xL in ERK- or/and p38-related pathways. The balance between ERK and p38 may determine the iodine-modulated Bcl-xL expression. The high ERK/p38 activity ratio up-regulated Bc1-xL and enabled the tumor cells to resist chemotherapy, whereas the low ERK/p38 down-regulated Bc1-xL and sensitized the tumor cells to chemotherapy. Taken together, iodine plays a critical role in apoptosis of thyroid cancer cells induced by chemotherapeutic agents. The balance between ERK and p38 may determine cell survival and death through modulating Bcl-xL expression in thyroid cancer cells. The findings provide some new insights into the roles of iodine in chemotherapeutic agents-induced apoptosis in thyroid cancer cells.
To summarize, iodine-induced apoptotic effects on thyroid cancer cells is a key pathway for iodine to influence thyroid cancer development and chemotherapy. Meanwhile MAPKs-related mutant p53, p21 and Bcl-xL expression are critical in deciding thyroid cancer cells survival and death. Moreover, iodine can influence chemotherapeutic agents-induced apoptosis through ERK/p38-mediated Bcl-xL expression.
Liu, Xiaohong.
"December 2009."
Adviser: Charles Andrew van Hasselt.
Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 111-146).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
"The effect of corticosteroid therapy on growth in Black South African children with nephrotic syndrome." Thesis, 1986. http://hdl.handle.net/10413/2433.
Повний текст джерелаThesis (M.Med.)-University of Natal, Durban, 1986.
"Investigation into the mechanism of action of corticosteroids to antagonise cisplatin- and motion-induced emesis." 2000. http://library.cuhk.edu.hk/record=b5890434.
Повний текст джерелаThesis (M.Phil.)--Chinese University of Hong Kong, 2000.
Includes bibliographical references (leaves 156-184).
Abstracts in English and Chinese.
Publications based on work in this thesis --- p.ii
Abstract --- p.iii
Acknowledgements --- p.vii
Chapter 1 --- INTRODUCTION --- p.1
Chapter 1.1 --- Corticosteroids --- p.2
Chapter 1.1.1 --- Chemical Structure of Steroids --- p.3
Chapter 1.1.2 --- Biosynthesis of Endogenous Corticosteroids --- p.3
Chapter 1.1.2.1 --- Regulation of Cortisol synthesis and negative feedback system --- p.4
Chapter 1.1.3 --- Biological Significance of Corticosteroids --- p.5
Chapter 1.1.3.1 --- Involvement of corticosteroids as anti-inflammatory drugs --- p.6
Chapter 1.1.3.2 --- Eicosanoid biosynthesis --- p.7
Chapter 1.1.3.3 --- Lipoxygenase pathway --- p.9
Chapter 1.1.3.4 --- Side-effects of prolonged use of corticosteroids --- p.9
Chapter 1.2 --- Organisation of the Emetic Reflex --- p.11
Chapter 1.2.1 --- Motor Pathway of Emetic Reflex --- p.12
Chapter 1.2.1.1 --- Retching and vomiting --- p.12
Chapter 1.2.1.2 --- Nausea --- p.13
Chapter 1.2.2 --- Components of the Emetic Reflex --- p.14
Chapter 1.2.2.1 --- The vomiting centre (VC) --- p.15
Chapter 1.2.2.2 --- Area postrema (AP) / Chemoreceptor trigger zone (CTZ) --- p.15
Chapter 1.2.2.3 --- The nucleus tractus solitarius (NTS) --- p.17
Chapter 1.2.2.4 --- Gastrointestinal tract and vagus nerves --- p.17
Chapter 1.2.2.5 --- Neurotransmitter receptors --- p.18
Chapter 1.3 --- Chemotherapy-Induced Emesis --- p.19
Chapter 1.3.1 --- Cancer as a cause of mortality in Man --- p.20
Chapter 1.3.2 --- Chemotherapeutic Agents --- p.20
Chapter 1.3.2.1 --- Different classes --- p.20
Chapter 1.3.2.2 --- Emetogenic potential --- p.21
Chapter 1.3.3 --- Cisplatin-Induced Emesis --- p.23
Chapter 1.3.3.1 --- Unfavourable effects associated with chemotherapy-induced nausea and emesis --- p.24
Chapter 1.3.3.2 --- Anticipatory nausea and vomiting --- p.24
Chapter 1.3.3.3 --- Profile of cisplatin-induced emesis --- p.25
Chapter 1.3.4 --- Animal Models of Cisplatin-Induced Acute and Delayed Emesis --- p.26
Chapter 1.3.5 --- Mechanisms and Pathways Involves in Chemotherapy-Induced Emesis --- p.28
Chapter 1.3.6 --- Anti-Emetic Drugs for the Treatment of Chemotherapy-Induced Emesis --- p.31
Chapter 1.3.6.1 --- 5-HT3 receptor antagonists --- p.31
Chapter 1.3.6.2 --- Dopamine receptor antagonists --- p.33
Chapter 1.3.6.3 --- Benzodiazepines --- p.35
Chapter 1.3.6.4 --- Cannabinoids --- p.35
Chapter 1.3.6.5 --- Antihistamines and anticholinergics --- p.35
Chapter 1.3.6.6 --- NK1 receptor antagonists --- p.37
Chapter 1.3.6.7 --- Corticosteroids --- p.38
Chapter 1.3.6.8 --- Multi-agent anti-emetic regimens --- p.39
Chapter 1.4 --- Motion-Induced Emesis --- p.41
Chapter 1.4.1 --- Incidence --- p.42
Chapter 1.4.2 --- Mechanisms and Pathways Involved in Motion Sickness --- p.43
Chapter 1.4.2.1 --- Importance of the vestibular apparatus --- p.44
Chapter 1.4.2.2 --- Importance of the area postrema --- p.45
Chapter 1.4.2.3 --- The nucleus tractus solitarius --- p.46
Chapter 1.4.2.4 --- Hormone and neurotransmitters --- p.46
Chapter 1.4.3 --- Animal models in Motion-Induced Emesis --- p.47
Chapter 1.4.4 --- Anti-Emetic Drugs for the Treatment of Motion Sickness --- p.48
Chapter 1.4.4.1 --- Anticholinergics --- p.49
Chapter 1.4.4.2 --- Antihistamines --- p.49
Chapter 1.4.4.3 --- Non-selective muscarinic and histamine receptor antagonists --- p.51
Chapter 1.4.4.4 --- Sympathomimetics --- p.51
Chapter 1.4.4.5 --- NK1i receptor antagonists --- p.51
Chapter 1.4.4.6 --- 5-HT1A agonists --- p.52
Chapter 1.4.4.7 --- 5-HT2 receptor agonist --- p.52
Chapter 1.4.4.8 --- Arginine vasopressin (AVP) antagonists --- p.53
Chapter 1.4.4.9 --- Opioid receptor agonists --- p.53
Chapter 1.4.4.10 --- Dexamethasone and hormone levels --- p.54
Chapter 1.4.4.11 --- Other anti-emetic drugs --- p.55
Chapter 1.5 --- Aims of the Studies --- p.56
Chapter 2 --- Methods --- p.59
Chapter 2.1 --- Cisplatin-Induced Emesis Studies --- p.60
Chapter 2.1.1 --- Animals --- p.60
Chapter 2.1.2 --- Induction and Measurement of Emesis --- p.60
Chapter 2.1.3 --- The Effects of Corticosteroids on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.63
Chapter 2.1.4 --- "The Effects of Dexamethasone (1 mg/kg, i.p.) Administered as an Intervention Treatment on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.63
Chapter 2.1.5 --- The Effects of Cortrosyn Depot (Tetracosactrin) on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.63
Chapter 2.1.6 --- The Effects of Metyrapone on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.64
Chapter 2.1.7 --- The Effects of Indomethacin on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.64
Chapter 2.1.8 --- "The Effects of DFU and L-745,337 Administered as an Intervention Treatments on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.64
Chapter 2.1.9 --- "The Effects of MK-886 (L-663,536) on Cisplatin-Induced Acute and Delayed Retching and Vomiting" --- p.65
Chapter 2.1.10 --- The Effects of a Combination of Indomethacin and MK-886 on Cisplatin- Induced Acute and Delayed Retching and Vomiting --- p.65
Chapter 2.1.11 --- Statistical Analysis --- p.66
Chapter 2.2 --- Motion-Induced Emesis Studies --- p.67
Chapter 2.2.1 --- Animals --- p.67
Chapter 2.2.2 --- Measurement of Emesis --- p.67
Chapter 2.2.3 --- Induction of Emesis in Motion-Naive Suncus murinus: Effects of Glucocorticoids --- p.68
Chapter 2.2.4 --- Induction of Emesis in Motion-Sensitive Suncus murinus: Effects of Dexamethasone --- p.70
Chapter 2.2.5 --- Preparation of Serum --- p.72
Chapter 2.2.6 --- Measurement of Serum Cortisol by Enzyme-Linked Immunoassay (ELISA) --- p.72
Chapter 2.2.6.1 --- Immunoassay kit --- p.72
Chapter 2.2.6.2 --- Assay procedures --- p.73
Chapter 2.2.7 --- Measurement of Serum Adrenocorticotrophin (ACTH) by Radioimmunoassay (RIA) --- p.75
Chapter 2.2.7.1 --- Immunoassay kit --- p.75
Chapter 2.2.7.2 --- Assay procedures --- p.76
Chapter 2.2.8 --- Statistical Analysis --- p.79
Chapter 3 --- Results --- p.81
Chapter 3.1 --- Cisplatin-Induced Emesis --- p.82
Chapter 3.1.1 --- General Profile of Emesis Induced by Cisplatin --- p.82
Chapter 3.1.2 --- Antagonism of Cisplatin-Induced Emesis by Corticosteroids --- p.82
Chapter 3.1.3 --- "The Effect of Dexamethasone (1 mg/kg, i.p.) Administered as an Intervention Treatment on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.84
Chapter 3.1.4 --- The Effect of Cortrosyn Depot (Tetracosactrin) on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.85
Chapter 3.1.5 --- The Effect of Metyrapone on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.85
Chapter 3.1.6 --- "The Effect of Indomethacin, DFU and L-745,337 on Cisplatin-Induced Acute and Delayed Retching and Vomiting" --- p.86
Chapter 3.1.7 --- The Effect of MK-886 on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.88
Chapter 3.1.8 --- The Effect of Combination of Indomethacin and MK-886 on Cisplatin- Induced Acute and Delayed Retching and Vomiting --- p.89
Chapter 3.2 --- Motion-Induced Emesis --- p.91
Chapter 3.2.1 --- General Effect of Motion on Serum Cortisol and ACTH Levelsin Motion Naive Suncus murinus --- p.91
Chapter 3.2.2 --- The Effect of Glucocorticoids on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion-Naive Male Suncus murinus --- p.92
Chapter 3.2.2.1 --- Effect of dexamethasone --- p.92
Chapter 3.2.2.2 --- Effect of betamethasone --- p.93
Chapter 3.2.2.3 --- Effect of methylprednisolone --- p.93
Chapter 3.2.3 --- The Effect of Glucocorticoids on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion Naive Female Suncus murinus --- p.94
Chapter 3.2.3.1 --- Effect of dexamethasone --- p.94
Chapter 3.2.3.2 --- Effect of betamethasone --- p.95
Chapter 3.2.3.3 --- Effect of methylprednisolone --- p.95
Chapter 3.2.4 --- The Effect of Dexamethasone on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion-Sensitive Suncus murinus --- p.96
Chapter 3.2.4.1 --- Effect of dexamethasone on male motion-sensitive animals --- p.97
Chapter 3.2.4.2 --- Effect of dexamethasone on female motion-sensitive animals --- p.97
Chapter 4 --- Discussion --- p.131
Chapter 4.1 --- "Cisplatin (5 mg/kg, i.p.)-Induced Emesis in Control Animals" --- p.132
Chapter 4.2 --- Anti-Emetic Action of Corticosteroids in the Ferret --- p.133
Chapter 4.3 --- Metyrapone Study --- p.138
Chapter 4.4 --- Cortrosyn Depot Study --- p.139
Chapter 4.5 --- Role of Cycloxygenase --- p.141
Chapter 4.6 --- Role of 5-Lipoxygenase --- p.143
Chapter 4.7 --- Duel Inhibition of Cycloxygenase and 5-Lipoxygenase --- p.144
Chapter 4.8 --- Anti-Emetic Potential of Glucocorticoids in Suncus murinus --- p.145
Chapter 4.9 --- General Summary --- p.149
Appendix I --- p.152
Appendix II --- p.154
References --- p.156
"Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and mitochondrial dysfunction." Thesis, 2010. http://library.cuhk.edu.hk/record=b6075047.
Повний текст джерелаIt is widely accepted that human islet amyloid polypeptide (hIAPP) aggregation plays an important role in the loss of insulin-producing pancreatic beta cells. Insulin secretion impairment and cell apoptosis can be due to mitochondrial dysfunction in pancreatic beta cells. hIAPP-induced cytotoxicity is mediated by the generation of reactive oxygen species (ROS). Phycocyanin (PC) is a natural compound from blue-green algae that is widely used as food supplement. Currently, little information is available about the effect of hIAPP on mitochondrial function of beta cells and protection of PC against hIAPP-induced cytotoxicity. In this thesis, I hypothesize that hIAPP may impair beta cell function with the involvement of mitochrondrial dysfunction, and this effects could be attenuated by PC. Therefore, the aim of this study was to investigate the role of mitochondria in hIAPP-induced apoptosis, the in vitro protective effects of PC and explore the underlying mechanisms.
It was found that hIAPP induced apoptosis in INS-1E cells with the disruption of mitochondrial function, as evidenced by ATP depletion, mitochondrial mass reduction, mitochondrial fragmentation and loss of mitochondrial membrane potential (DeltaPsim). Further molecular analysis showed that hIAPP induced changes in the expression of Bcl-2 family members, release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria into cytosol, activation of caspases and cleavage of poly (ADP-ribose) polymerase. Interestingly, the hIAPP-induced mitochondrial dysfunction in INS1-E cells was effectively restored by co-treatment with PC.
Our results showed that hIAPP inhibited the INS-1E cell growth in a dose-dependent manner. However, cytotoxicity of hIAPP was significantly attenuated by co-incubation of the cells with PC. hIAPP induced DNA fragmentation and chromatin condensation, which were key characteristics of cell apoptosis. These changes were inhibited by PC as examined by TUNEL assay and DAPI staining. Moreover, PC significantly prevented the hIAPP-induced overproduction of intracellular ROS and malonaldehyde (MDA), as well as changes of activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Furthermore, hIAPP triggered the activation of mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinase (JNK) and p38 kinase, and these effects were effectively suppressed by PC.
Taken together, I have demonstrated for the first time the involvement of mitochondrial dysfunction in hIAPP-induced INS-1E cell apoptosis, which was attenuated by PC through attenuating oxidative stress, modulating JNK and p38 pathways and reducing mitochondrial dysfunction.
Li, Xiaoling.
Adviser: Juliana Chung Ngor Chan.
Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 150-159).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.