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1
Chittchang, Montakarn Johnston Thomas P. "Effect of secondary structure on paracellular transport of polypeptides." Diss., UMK access, 2004.
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Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004."A dissertation in pharmaceutical sciences and chemistry." Advisor: Thomas P. Johnston. Typescript. Vita. Description based on contents viewed Feb. 23, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 202-223). Online version of the print edition.
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Cook, Andrew T. "The effect of accelerated aging on peelable medical products seals /." Online version of thesis, 1994. http://hdl.handle.net/1850/11980.
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Weise-Kelly, Lorraine Ann. "Drug-induced ataxia : effect of the self-administration contingency /." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0030/NQ66245.pdf.
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Dalal, Suntanu. "Amphetamine drugs potentiate morphine analgesia in the formalin test." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55488.
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There has been a great deal of research investigating drug combinations which can increase analgesia. A number of studies have been conducted with one particular combination--opioids combined with the amphetamine drugs. Despite the existing literature, this combination is rarely used in clinical practice. One purpose of this thesis is to review the literature pertaining to the opioid-amphetamine combination. Another purpose of this thesis is to investigate whether dextroamphetamine sulfate ($ circler$Dexedrine) can potentiate morphine sulfate analgesia in rats in the formalin test (Experiment 1). To investigate whether these results can be generalized to another psychostimulant, methylphenidate hydrochloride ($ circler$Ritalin) is used in Experiment 2. Methylphenidate has been chosen instead of another amphetamine drug because it is currently being used in clinical studies without supporting evidence from animal studies. The results of the two experiments indicate that low doses of d-amphetamine and methylphenidate can potentiate the analgesic effects of morphine.
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Bai, Shuang. "Effect of immunosuppressive agents on drug metabolism in rats." Thesis, Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3008270.
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Church, Donna Lea. "Depot medroxyprogesterone acetate discontinuation after weight gain in 17-19 year old adolescent girls." CSUSB ScholarWorks, 2002. https://scholarworks.lib.csusb.edu/etd-project/2047.
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Depot medroxyprogesterone acetate (DMPA) is a long acting progesterone only contraceptive agent. Side effects such as irregular bleeding patterns and weight gain are attributed to discontinuation. The purpose of this study was to describe depot medroxyprogesterone acetate discontinuation after weight gain in 17 to 19 year-old adolescent girls.
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Hammann, Felix. "Prediction of transport, pharmacokinetics, and effect of drugs /." Basel : [s.n.], 2009. http://edoc.unibas.ch/diss/DissB_8905.
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Chawla, Monica Kapoor 1950. "THE ROLE OF SEVERAL DRUGS AND COSOLVENTS ON INFUSION RELATED PHLEBITIS (THERMOGRAPHY)." Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/276915.
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Goble, David. "The impact of low to moderate alcohol consumption on different types of human performance." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1006042.
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Despite extensive research into the effects of alcohol consumption, there is no clear understanding into the mechanisms underlying human information processing impairment. The acute consumption of alcohol was investigated to determine the implications for human information processing capabilities, and to identify the extent to which these implications were stage-specific. Further aims included the investigation and quantification of caffeine-induced antagonism of alcohol impairment. Moreover, the aforementioned relationships were investigated in morning versus evening conditions. A test battery of six resource-specific tasks was utilised to measure visual perceptual, cognitive and sensory-motor performance, fashioned to return both simple and complex measures of each task. The tasks implemented were: visual perceptual performance (accommodation, visual detection, visual pattern recognition); cognition (memory recall- digit span); and motor output (modified Fitts‟ and a driving simulated line-tracking). Performance measures were recorded by the respective computer based tasks. Physiological variables measured included heart rate frequency, heart rate variability (RMSSD, High and Low Frequency Power) and body temperature. Saccade speed, saccade amplitude, pupil size and fixation duration were the oculomotor parameters measured. Three groups of participants (alcohol, caffeine+alcohol and control) n=36 were studied, split evenly between sexes in a mixed repeated/non-repeated measures design. The control group performed all test batteries under no influence. The alcohol group performed test batteries one and two sober, and three and four under the influence of a 0.4 g/kg dose of alcohol. Group caffeine+alcohol conducted test battery one sober, two under the effect of caffeine only (4 mg/kg), and three and four under the influence of both caffeine and alcohol (0.4 g/kg). The third test battery demonstrated the effects of alcohol during the inclining phase of the blood alcohol curve, and the fourth represented the declining phase. Morning experimentation occurred between 10:00 - 12: 45 and 10:30 -13:15 with evening experimentation between 19:00 - 21:30 and 19:30 - 22:00. Acute alcohol consumption at a dose of approximately 0.4 g/kg body weight effected an average peak breath alcohol concentration of 0.062 % and 0.059 % for the alcohol and caffeine+alcohol groups respectively. Task-related visual perceptual performance demonstrated significant decrements for simple reaction time, choice reaction time and error rate. Cognitive performance demonstrated no significant performance decrements, while motor performance indicated significant decrements in target accuracy only. Physiological parameters in response to alcohol consumption showed significantly decreased heart rate variability (RMSSD) in the modified Fitts‟ task only. A significant decrease in saccade amplitude in the memory task was the only change in oculomotor parameters. Prior caffeine consumption demonstrated limited antagonism to task-related alcohol impairment, significantly improving performance only in reduced error rate while reading. Caffeine consumption showed stimulating effects on physiological parameters, significantly increasing heart rate and heart rate variability when compared to alcohol alone. The design of the tasks allows for comparison between complex and simple task performance, indicating resource utilisation and depletion. Complex tasks demonstrated higher resource utilisation, however with no statistical performance differences to simple tasks. Physiological parameters showed greater change in response to alcohol consumption, than did the performance measures. Alcohol consumption imposed significant changes in physiological and oculomotor parameters for cognitive tasks only, significantly increasing heart rate frequency and decreasing heart rate variability, skin temperature and saccade amplitude. Caffeine consumption showed no antagonism of alcohol-induced performance measures. Physiological measures showed that caffeine consumption imposed stimulating effects in only the neural reflex and memory tasks, significantly increasing heart rate frequency and heart rate variability. Prior caffeine consumption significantly decreased fixation duration in the memory task only. The time of day at which alcohol was consumed demonstrated significant performance and physiological implications. Results indicated that morning consumption of alcohol imposes greater decrements in performance and larger fluctuations in physiological parameters than the decrements in evening experimental sessions. It can be concluded that alcohol consumption at a dose of 0.4 g/kg affects all stages in the information processing chain. Task performance indicates that alcohol has a greater severity on the early stages of information processing. Conversely, under the influence of alcohol an increased task complexity induces greater effects on central stage information processing. In addition, caffeine consumption at a dose of 4 mg/kg prior to alcohol does not antagonise the alcohol-induced performance decrements.
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Hoa, Nguyen Khanh. "Assessment of anti-diabetic effect of Vietnamese herbal drugs /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-585-2/.
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Elliott-Pearce, Ruth Ann. "The effect of drugs on isolated detrusor muscle contraction." Thesis, University of Leicester, 1996. http://hdl.handle.net/2381/34339.
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Detrusor instability is the commonest type of urinary incontinence in the elderly and is present in up to 50% of patients attending continence clinics. Treatment of this condition, aimed at reducing uncontrollable detrusor contractions, is at present unsatisfactory. For example, calcium antagonists are cliniclly disappointing and studies were carried out to investigate why they are ineffective. Rats were treated with nimodipine for 8 days or with a single dose. Treatment for 8 days had no effect on isolated detrasor contraction but a single dose reduced detrasor contractile response. It is propossed that chronic treatment with nimodipine caused an up-regulation of calcium channels as a compensatory mechanism. Oestrogens have been shown to have an inhibitory effect on detrusor muscle contraction after in vitro and in vivo treatment. In post-menopausal women with a uterus unopposed oestrogens should not be given, but progesterone has anti-oestrogenic actions. When rats were treated with oestrogen and progesterone for 8 days, there was no effect on rat detrasor contractile response. An anti-oestrogenic effect of progesterone has therefore been demonstrated in rat detrusor smooth muscle. Caffeine has been shown to increase detrasor pressme on bladder filling in patients with detrusor instability. The effect of low concentrations of caffeine on the contractile response of isolated human and rat detrusor muscle was therefore determined. Caffeine was found to have only a slight potentiating effect on isolated human and rat detruosr muscle contraction. The results in this thesis have important clinical imphcations for the treatment of detrusor instability. It may be more effective to administer calcium antagonists in an intermittent manner. Oestrogens are better given alone or with the lowest possible dose of progestogens. Caffeine would not be contraindicated in patients with detrusor instability.
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Gouws, Stephanus Andries. "The impact of hospital surveillance programmes on the incidence of adverse drug reaction reporting in a South African teaching hospital." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/27186.
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Post-marketing surveillance refers to any non-experimental or observational study, method, or monitoring strategy that is applied to obtain information on drug experience (primarily adverse) after a drug has been approved for clinical use. One of the major problems in post-marketing surveillance studies is the lack or under-reporting of drug experiences by health care professionals. This study was developed to describe the impact of three different prescription event monitoring programmes on the reporting of adverse drug reactions (ADR's) in the hospital situation. The intensive ADR monitoring programme and two voluntary ADR monitoring programmes which followed were conducted in the medical wards of an urban teaching and referral hospital. All patients admitted to the designated wards were monitored by a dedicated pharmacist in the intensive programme, ward pharmacists in the first voluntary programme and by medical and nursing staff in the second voluntary programme. The pharmacist monitored a cohort of patients prospectively in two medical wards for a period of three months. The patient's record was linked with any suspected ADR. All details, i.e. patient drug orders, characteristics and ADR description, were recorded and then reported. From 228 patients monitored, 25 cases have been reported. The impact of the intensive ADR monitoring programme was a reporting rate of 11 percent. Reports were received on ADR's of a particularly mild, common and pharmacologically predictable (type A) nature. The first voluntary ADR monitoring programme comprised the reporting of suspected AD R's and the recording of drug orders for the patients and the patient characteristics. The ward pharmacists monitored for suspected AD R's in all patients during their regular ward rounds. Six cases were reported in a population of 1506 patients monitored during the three months. The reports were mainly on moderate to severe suspected AD R's of pharmacologically unpredictable (type B) nature. The rate of reports received by the surveillance unit in this study was 4 reports per ward pharmacist per annum. The second voluntary ADR monitoring programme comprised the prospective monitoring of 1555 patients by medical and nursing staff during their stay at the designated medical wards during the three month period. Patients were monitored for any ADR and when an ADR was suspected, the patient characteristics and drug orders were recorded and reported to the surveillance unit. Ten cases were reported represented by six reports from doctors and four by sisters. The reporting rate was 2 reports per doctor in four years and 3 reports for each member of the nursing team in 5 years. Reports were mainly received on moderate to severe suspected ADR's of a pharmacologically unpredictable (type B) nature.
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Brophy, Conor Jane. "The effect of theophylline on the respiratory and quadriceps femoris muscles in man /." Title page, contents and abstract only, 1992. http://web4.library.adelaide.edu.au/theses/09MD/09mdb873.pdf.
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Davis, Christopher John. "Neuropharmacological investigations into the mechanisms of emesis caused by cytotoxic drugs and radiation." Thesis, University of Oxford, 1988. https://ora.ox.ac.uk/objects/uuid:b9afefde-a43e-415e-8754-ed2a8eaac620.
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Chu, Yu-Hsuan. "Custom Fluorophores for Investigating the Cellular Uptake Mechanisms and Side-Effects of Pharmaceuticals." PDXScholar, 2015. http://pdxscholar.library.pdx.edu/open_access_etds/2343.
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There is a significant current need to elucidate the molecular mechanisms of the side-effects caused by widely-used pharmaceuticals. Examples include the acute nephrotoxicity and irreversible ototoxicity promoted by the cationic drugs gentamicin and cisplatin. Gentamicin is an aminoglycoside antibiotic used for the prevention and treatment of life-threatening gram-negative bacterial infections, such as tuberculosis and meningitis. Cisplatin is used to treat a broad spectrum of cancers including head and neck, ovarian, cervical, stomach, bladder, sarcoma, lymphoma, testicular cancer and others.
The objective of this study is to design and synthesize rhodamine derivatives that can be used for the construction of geometrically well-defined cationic drug conjugates. The long-term goal is to use the conjugates as tools to aid in elucidating the properties and identities of ion channels involved in the uptake of cationic pharmaceuticals into kidney and cochlear hair cells. This will shed light on the origin and potential prevention of unwanted side effects such as nephrotoxicity and ototoxicity associated with specific cationic drugs.
A series of extended rhodamine analogs with reactive groups for biomolecule conjugation has been synthesized. These fluorophores show similar spectral properties to their prototype, Texas Red succinimidyl ester (TR-SE). However, they contain rigid linkers between the fluorophore and amine-reactive moiety. The resultant gentamicin conjugates of these materials are rigidified enabling one to assess channel pore dimensions without the confounding issue of conjugate folding. Preliminary cell studies are promising, as one observes reduced gentamicin uptake in both kidney and sensory hair cell upon systematically increasing the dimension of the fluorophore. This work has enabled us to tentatively assign the maximum dilated MET channel pore size as between 1.44 nm to 1.56 nm. However, this preliminary finding, though encouraging, needs further validation via ongoing studies with larger diameter fluorophore conjugates,
A cisplatin-Texas Red conjugate has also been synthesized to enable studies of cellular uptake mechanisms. This conjugate preserves not only the spectral properties of Texas Red after conjugation, but also the cytotoxicity of cisplatin. This has been validated in zebrafish. The series of rhodamine probes that have been conjugated to gentamicin should be similarly useful for cisplatin studies. These studies are planned. Additional future work includes the synthesis of semi-flexible (glycol) and flexible (alkyl) linkers to evaluate structure-activity relationships.
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Lange, Jeremy David. "The effect of anti-malarial drugs on the pituitary gland." Thesis, University of Leeds, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238726.
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Figueiredo, João Daniel Amaral. "The effect of anticancer drugs prodiginines in PP1 in melanoma." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/6861.
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Mestrado em Biomedicina MolecularUm dos principais mecanismos reguladores da função celular é a fosforilação de proteínas. É de focar que a fosforilação anormal de proteínas-chave pode estar associada a várias patologias, incluindo o cancro. Embora já existam muitos estudos sobre cinases no cancro, o conhecimento sobre as fosfatases que antagonizam a acção das cinases é muito menos. A PP1, uma das principais proteínas fosfatase de serina/treonina expressa em todas as células eucarióticas, está envolvida em vários processos celulares incluindo apoptosis e ciclo celular. Na realidade, diversos estudos demonstram que a PP1 regula variadas proteínas que são elementos-chave no processo de tumorigenesis. A AKT, uma cinase serina/treonina que se encontra desregulada em vários tipos de cancro, é um factor crucial na progressão e sobrevivência de melanoma. Prodigiosina, um membro da família de metabolitos secundários tripirrolicos pigmentados de vermelho, as prodigininas, demonstra propriedades anticancerigenas em vários tipos de cancro. Na verdade alguns estudos verificaram que a AKT é desfosforilada pela prodigiosina embora ainda seja desconhecido o mecanismo pelo qual tal acontece. Dada a importância da AKT na progressão e sobrevivência do melanoma e a capacidade da PP1 em desfosforilar a AKT é possível que a PP1 esteja envolvida em tal mecanismo. Os resultados preliminares demonstraram que a PP1 liga-se a um membro da família das prodigininas provando a interacção entre estas moléculas. Por outro lado, ensaios em linhas celulares de melanoma usando tratamentos com prodigiosina e cantaridina, um inibidor da PP1, demonstraram que a prodigiosina afecta isoformas da PP1 diferencialmente. Estes resultados sugerem que a prodigiosina actua em duas vias de sinalização distintas em melanoma, a via da AKT e a da MAPK, uma vez que alteração nos níveis de PP1α, uma das isoformas da PP1, se correlaciona com a variação dos níveis de fosforilação da AKT e as mudanças nos níveis da PP1γ com a variação dos níveis de fosforilação da MAPK. Com estes resultados propomos um modelo de como a prodigiosina desfosforila a AKT e como este processo contribui para a indução da morte celular em células de melanoma. Esperamos que este modelo ajude na compreensão do mecanismo de acção da prodigiosina bem como no reconhecimento das fosfatases como novos alvos terapêuticos no tratamento de cancro.
Protein phosphorylation is a major regulatory mechanism for cell function. It is noteworthy that several pathologies, including cancer to be associated with abnormal phosphorylation of key proteins. Although many studies have addressed the kinases that are misregulated in cancer, much less is known about the phosphatases that counteract their actions. PP1, a major serine/threonine protein phosphatase that is ubiquitously expressed in all eukaryotic cells, is involved in many cellular processes including apoptosis and cell cycle. In fact, several studies demonstrate that PP1 regulates several proteins that are key elements in the tumorogenesis process. AKT, a serine/threonine kinase that is disregulated in several types of cancer is a crucial factor in melanoma progression and survival. Prodigiosin, a family member of the natural red pigmented tripyrrolic secondary metabolites, prodiginines, show anticancer properties in numerous types of cancer. In fact, some prodigiosin studies demonstrate that AKT is dephosphorylated by prodigiosin by an unknown mechanism. Given the importance of AKT in melanoma progression and survival and the capacity of PP1 to dephosphorylate AKT it is possible that PP1 is involved in this mechanism. Our preliminary results showed that PP1 binds to one member of prodiginine family proving the interaction between these molecules. On the other hand, experiments with melanoma cell lines, using prodigiosin and cantharidin, a PP1 inhibitor, treatments, demonstrate that prodigiosin affect differently PP1 isoforms. These results suggest that prodigiosin acts in a different way in two altered pathways in melanoma, AKT and MAPK, since the alterations in PP1α levels, one of PP1 isoforms, are correlated with the conversion in AKT dephosphorylation and the variations in PP1γ levels with the changes in MAPK dephosphorylation. Given these results we propose a model of how prodigiosin dephosphorylates AKT and how this process contributes to induce cell death in melanoma cells. We expect that this model helps to understand prodigiosin action mechanism as well as acknowledge phosphatases as a therapy target in cancer treatment.
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Ngamratanapaiboon, Surachai. "Metabolomics investigations of the effect of drugs on mammalian cells." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/41178/.
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Cell-based metabolomics using LC-MS systemizes the study of the uniqueness of small-molecule metabolite (metabolomes) profiles in cellular processes. Cell-based metabolomics can potentially be used in many applications for the study of biological perturbation from stimulants in cellular pathways. The advantages of cell-based metabolomics include ease of control and interpretation when compared to the study of human subjects and animal models. Furthermore, this method can decrease some highly challenging problems that occur in genomics, transcriptomics and proteomics. Nowadays, cell culture in metabolomics studies has been used in many applications. These include cell culture and bioreactor optimisation, phenotype classification, stimulant testing effect, target and toxicity analysis, metabolic networks determination and modelling, and biomarker and drug target discovery. In this study, the reverse phase-liquid chromatography-mass spectrometry and hydrophilic interaction chromatography-mass spectrometry for comprehensive metabolic profiling well suited to the untargeted analysis of non-polar and polar metabolites in mammalian cells were developed, optimized and validated. These methods can separate and detect most of hydrophobic and polar metabolites that are normally found in mammalian cell lines. After that the LC-MS methods were applied to assess the effects of drugs with known and unknown cellular metabolic effects on three mammalian cell lines, namely HMVECs for antipsychotics experiment, MCF-7 cells for cordycepin experiment and MIN6 cells for fluoxetine experiment by using untargeted metabolic profiling. The global effects of antipsychotics at high therapeutic dosage in HMVECs were investigated. The results support for the toxicity hypothesis with measurements that confirm previous findings and reveal the exact biological pathways of antipsychotic-altered BBB functions. It was found that antipsychotics may affect the bioenergetics pathway due to mitochondrial dysfunction resulted in ketoacidosis and inducing oxide stress by reactive oxygen species generation. In the MCF- cell experiment, the results of the untargeted metabolite profiling demonstrated the clear anti-breast cancer effects of cordycepin and pentostatin. By investigating the metabolite profiles, clear synergistic effects of cordycepin and pentostatin combined in comparison to cordycepin activity alone in MCF-7 cells was observed. Furthermore, the pathway analysis indicated that anti-breast cancer activity was mainly responsible for alterations in purine and pyrimidine metabolism and bioenergetics. Additionally, cordycepin may be involved in the inhibition of cell proliferation and differentiation, and the activation of cell apoptosis. The last experiment on MIN6 cells, the developed and optimized HILIC-MS approach in order to determine the biological pathways which are impaired by fluoxetine on glucose-stimulated insulin secretion on MIN6 cell lines was performed. It is found that fluoxetine may impair glycolysis, TCA and fatty acid metabolism on MIN6 cell lines. Moreover, it is also reveal that the alteration of biological pathways on MIN6 cells by known ETC inhibitors (rotenone (Complex I inhibitor) antimycin (Complex III inhibitor)) and azide (a complex IV inhibitor). From comparison with these ETC inhibitors, it is found that fluoxetine may have the same effect pattern with azide.
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Chak, Man-lee Charlotta, and 翟敏莉. "A retrospective study on the effectiveness of anti-ulcer drugs in the prevention of nonsteroidal inflammatory drugs (NSAID)-inducedgastrointestinal effects." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31971453.
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Gabriel, Kara Irene. "Effects of prenatal ethanol exposure and postnatal handling on cognition/behavior and hypothalamic-pituitary-adrenal stress responsiveness in Sprague-Dawley rats." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ56547.pdf.
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Howell, Leonard L. "An experimental analysis of rate constancy." Diss., Georgia Institute of Technology, 1985. http://hdl.handle.net/1853/29865.
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Au, May-lan Alma. "The effects of subcortical lesions on memory." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1987. http://hub.hku.hk/bib/B29648270.
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Solomon, Matthew D. "The effect of cost-sharing on the utilization of prescription drugs for chronically ill patients." Santa Monica, Calif. : Rand, 2005. http://www.loc.gov/catdir/toc/fy0612/2006279614.html.
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Silberstein, D. J. "The effect of renal failure on the elimination of drugs by the liver." Thesis, University of Leeds, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379649.
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Ravaglia, Davide. "Modelling social behavior of Drosophila Melanogaster under the effect of drugs." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/18747/.
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Questa tesi affronta il problema di studiare il comportamento cognitivo negli animali attraverso metodi di analisi statistica e modelli dinamici stocastici. Negli esperimenti analizzati sono stati utilizzati degli esemplari di Drosophila Melanogaster confinati in un'arena a quali sono state somministrate droghe diverse in diversi esperimenti; parte integrante dello studio riguarderà l'influenza di queste droghe.
Lo scopo è esaminare il comportamento cognitivo degli animali attraverso l'analisi statistica degli incontri tra esemplari che possono avvenire sia per una situazione casuale che per una decisione dell'animale stesso. Per evidenziare la presenza di questa interazione sociale è stato prodotto un modello nullo dell'esperimento: diversi parametri estratti dai dati in possesso permettono la generazione di percorsi casuali. Assumendo la sua capacità di rappresentazione, differenze significative dal modello nullo indicheranno la presenza di comportamenti cognitivi.
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Tory, Rita. "The study of the effect of immunosuppressive drugs on lipid metabolism." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/7593.
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Introduction:
Lipid abnormalities including increased total cholesterol, triglycerides, and lowdensity
lipoprotein-cholesterol have been frequently reported in renal transplantation
and could be involved in the high frequency of cardiovascular disease in this
population. Immunosuppressive therapy appears to be a main factor that influences the
post-transplant lipid profile. Cyclosporine A (CsA), rapamycin (RAPA), tacrolimus
(TAC) and mycophenolate mofetil (MMF) are commonly used immunosuppressant in
solid organ transplant patients. Several of these immunosuppressive agents including
CsA, RAPA and TAC appear to have a significant effect on patient lipid level.
Although RAPA does not seem to cause nephrotoxicity as commonly seen in patients
treated with CsA or TAC, it seems to be associated with an incremental increase in
triglyceride level. However, the immunosuppressive-induced hyperlipidemia has not
been sufficiently described.
Purpose:
Our aim was to determine the effects of these drugs in vitro on key regulatory
enzymes of lipid metabolism; Cholesteryl Ester Transfer Protein (CETP), hepatic lipase
(HL) and lipoprotein lipase (LPL) activity within human plasma, as well as the in vivo
effects of TAC on these enzymes in renal transplant patients. In addition, we also
investigated the effects of RAPA and TAC on cholesterol efflux from human THP-l
macrophages.
Methods:
The effects of CsA, TAC, RAPA and MMF on CETP, HL and LPL activity
were first determined in vitro in human normolipidemic plasma and post-heparin
normal human plasma, respectively. We further investigated the in vivo effects of TAC
on these enzymes activities in renal transplant patients for one month following
transplantation. The cholesterol efflux study was conducted independently to assess the
effects of RAPA and TAC on ApoA-I- and HDL-mediated cholesterol efflux from
human THP-l macrophages, as well as adenosine-triphosphate binding cassette
(ABC)Al and ABCG1 protein expressions in these cells.
Results:
Our in vitro CETP study showed that CsA and RAPA induced CETP activity in
human normolipidemic plasma in a dose-dependant manner. Although, none of these
drugs, CsA, TAC, RAPA and MMF affected in vitro HL activity, these drugs
suppressed the LPL activity in the post-heparin plasma. Unlike TAC, RAPA was
shown to decrease apoAl-mediated cholesterol efflux and ABCA1 protein expression in
human THP-l macrophages. In agreement with our in vitro result, our clinical study
demonstrated that TAC significantly increased triglyceride levels and reduced the LPL
activity in the renal transplant patients, regardless of the patients were on statin or not.
Conclusions:
These findings suggest that the increase in CETP activity, suppression in LPL
activity and inhibition in the cholesterol efflux following either CsA, RAPA or TAC
treatments observed in the present study may be associated with hypercholesterolemia
and hypertriglyceridemia seen in patients administered these drugs.
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Daley, Emma. "The effect of mitochondrial membranolytic drugs on brain tumours in vitro." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272349.
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黃尚行 and Sheung-hang Wong. "The gastric effects of ethanol and their modulation by drugs in rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1989. http://hub.hku.hk/bib/B31232048.
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Michaelsen, Maria Høtoft. "The effect of digestion and drug load on absorption of poorly water soluble drugs from self-nanoemulsifying drug delivery systems (SNEDDS)." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59178.
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Dopheide, Marsha M. "The effect of modafinil on psychostimulant-evoked [³H]dopamine release from rat striatal slices." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5952.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 20, 2007) Includes bibliographical references.
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Mc, Erlane Verna May. "The anti-tumour effect of AQ4N and its' enhancement using a gene therapy strategy." Thesis, University of Ulster, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272332.
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El-Eraky, Hala Mohammed Tawfik. "The effect of gender on the pharmacokinetic and pharmacodynamic properties of drugs affecting cardiac repolarization : a study of antiarrhythmic drugs." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394683.
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Liu, Xiaoling. "Determination of whether the effects of statin drugs are mediated by phosphoinostide 3-kinase." Virtual Press, 2004. http://liblink.bsu.edu/uhtbin/catkey/1306853.
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Phosphoinositide 3-kinases (PI3Ks) are a family of proteins involved in many different aspects of cell signaling. To date, eight different human PI3K isoforms have been identified, and distinct roles are beginning to emerge for each family member. Statins, HMG co-A reductase inhibitors used clinically to lower LDL cholesterol levels, also act through the PI3K signaling pathway to regulate cholesterol independent of their lipid-lowering effects. In an effort to discover the role of pl 10f3 in mediating non-lipid lowering effects of pravastatin, a mutant of p110(3 was overexpressed in human coronary artery endothelial cells (HCAEC) to form a dominant negative model (p110(3 DN). Silence si-RNA as an alterative tool was also optimized to diminish p110(3 protein expression successfully. HepG2 3: RE was used to monitor statins function by assaying luciferase expression. Results from these studies will determine the contribution of p110f3 in mediating selective cellular responses to statin.Department of Biology
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Van, der Weyde Marlene P. "The effects of the beta-adrenergic agonist, ritodrine, in the fetal lamb." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/30417.
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Ritodrine is a beta-adrenergic agonist commonly used to inhibit premature labor contractions in women. The primary goal of ritodrine tocolysis is to prolong gestation, however, other indications may include fetal distress. The purpose of the current study was to examine the metabolic and behavioral effects of ritodrine in the fetus, using the chronically instrumented pregnant sheep as an experimental model.
Ritodrine was infused continuously into 11 fetal lambs at a rate of 2.6 ug/minute for a period of 8, 12 or 24 hours. Samples were taken simultaneously at predetermined time periods from a fetal femoral artery, umbilical vein, maternal femoral artery and uterine vein for the analysis of fetal and maternal arterial and umbilical and uterine venous blood gases, acid-base status, hematocrit, ritodrine concentration, uterine and umbilical blood flow, and glucose, lactate and oxygen concentrations and fluxes. Cardiovascular and behavioral variables were monitored continuously.
The average concentration of ritodrine in fetal arterial plasma was 20.0 ± 2.7 ng/ml (range 9.5 to 3 4.7 ng/ml) at the end of the infusion. This concentration is within the range of cord levels obtained in ritodrine exposed human fetuses at birth (7 to 79 ng/mL) . Fetal arterial plasma ritodrine levels at 8 hours post-infusion were still sufficiently elevated to exert considerable fetal effects. The apparent tolerance of the fetus to given plasma levels of drug varied considerably among animals.
The infusion of ritodrine resulted in many typical beta-adrenergic receptor mediated responses in the fetus. Fetal arterial glucose levels rose to 79% above the control by the end of the infusion. This was associated with an increase in fetal glucose delivery (70% above the control), a decrease in the umbilical veno-arterial glucose concentration difference and a tendency for fetal glucose uptake to decline. Fetal arterial plasma lactate concentrations rose more than fivefold during the infusion of ritodrine. This was associated with a rise in fetal lactate delivery (540% above the control), a slight increase in the umbilical veno-arterial plasma lactate concentration difference and a tendency for fetal lactate uptake to rise.
Fetal oxygen consumption rose progressively and significantly throughout the infusion of ritodrine and during the first 8 hours of post-infusion, reaching a maximum of 22% above the control by 8 hours post-infusion. Umbilical blood flow remained unchanged, therefore umbilical oxygen delivery was not increased to meet the additional oxygen demands of the fetus. The rise in fetal oxygen consumption was hence accomplished through an increase in fetal fractional oxygen extraction (from a control value of 32.0±1.1% to a maximum of 51.6±1.8% by 1.5 hours of infusion). The rise in fetal oxygen extraction resulted in concurrent declines in fetal arterial Po₂ (78% of the control) and O₂ content (55% of the control) and a widening of the veno-arterial oxygen content difference. By the end of the infusion, umbilical venous Po₂ and O₂ content values had also fallen significantly to 78% and 75% of the control respectively. These latter changes resulted in a concurrent 25% decline in fetal oxygen delivery which in turn contributed to the rise in fetal oxygen extraction.
Fetal arterial and umbilical venous pH declined rapidly and significantly from control values of 7.370±0.004 and 7.401±0.005 to 7.274±0.025 and 7.306±0.023 respectively by the end of the infusion. The acidemia was reflected by significant declines in base excess values and appeared to be entirely metabolic in nature, resulting from elevated blood lactate levels. The acidemia likely contributed to the progressive fall in fetal blood O₂ content through a rightward shift of the oxyhemoglobin dissociation curve (Bohr effect).
The rise in fetal oxygen consumption was reflected by a similar (although nonsignificant) increase in uterine oxygen consumption. Uteroplacental oxygen consumption appeared to remain unaltered. The rise in uterine oxygen consumption was not accompanied by a corresponding increase in uterine oxygen delivery, hence uterine oxygen extraction rose to 23.8±1.9% (from a control value of 19.5±1.6%) by 1.5 hours post-infusion. The rise in uterine oxygen extraction resulted in significant declines in uterine venous Po₂ and CO₂ values which likely contributed to the fall in fetal oxygen delivery.
Fetal heart rate increased significantly to 21% (34 beats per minute, bpm) above the control (162±7 bpm) during the first 1.5 hours of ritodrine infusion. It remained elevated by an average of 16% (26 bpm) throughout the remainder of the infusion and the first 8 hours of post-infusion, returning to the control by the end of the post-infusion period. Fetal arterial pressure remained unchanged from the control (46.2±1.5 mm Hg).
The incidence of fetal breathing activity fell significantly from an overall average control value of 43.2±2.6% to an average of 28.1±6.8% during the ritodrine infusion period. In most animals, breathing was most depressed near the end of the infusion. The incidence of low voltage electrocortical (ECoG) activity also fell significantly by an average of 7.5% while that of high voltage ECoG rose by 7.3%. Alterations in intermediate voltage activity were not observed. The incidence of fetal rapid eye movement also tended to fall by an average of 8.2% during the infusion of ritodrine. These behavioral changes may have resulted from the development of fetal hypoxemia, rather than as a direct effect of ritodrine.
In conclusion, these data have demonstrated that ritodrine infusion to fetal lambs results in significant physiological and behavioral changes in the fetus. These effects may put the fetus at risk, particularly in situations where fetal oxygen delivery is already reduced, as in various states of compromised pregnancy.Medicine, Faculty of
Obstetrics and Gynaecology, Department of
Graduate
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Zeitz, Christopher John. "Acute drug effects on the heart-haemodynamic, pharmacologic and metabolic correlations." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phz48.pdf.
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Addenda and corrigenda inserted on verso of back end paper. Includes: Publications and communications to learned societies (p. 4-5). Bibliography: leaves 272-286. Examines the acute myocardial uptake of drugs, particularly perindoprilat and enalaprilat in humans. The uptake of these agents is examined, together with the haemodynamic, metabolic and biochemical effects. In particular, the impact of these agents on angiotensin and bradykinin peptides both within the heart and peripherally is described. The acute effects of a range of cardioactive drugs upon the left ventricular force-interval relationship is examined.
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Chehresa, Azita. "Benzimidazole-resistance and associated changes in life history traits of Heligmosomoides polygyrus (Nematoda) in mice." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=42002.
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Association between albendazole anthelmintic resistance and a panel of life history traits in Heligmosomoides polygyrus was investigated both prior to and during drug-selection. Associations prior to anthelmintic application were studied in ten independent lines isolated without drug treatment from a susceptible stock population by random genetic drift. Variation among lines was detected in several life history traits (i.e., establishment, development and survival), and, despite lack of previous exposure to albendazole, lines also varied in their tolerance to the drug. No significant correlations were detected between drug-tolerance and any of the life history traits after 11 generations of isolation. The apparent lack of fitness differential between lesser and more drug-tolerant individuals of the susceptible population is not in accordance with the assumption that the low frequency of drug tolerant individuals in the susceptible population is explained by their lower fitness, but is consistent with the neutral theory. Associations between life history traits and drug resistance were also studied using two lines selected for albendazole resistance from the stock population, and two control lines exposed to the same monthly passage procedure but not to the drug. After 10 generations of selection, drug resistance increased from an LC50 of 0.48 $ mu$M to 2.03 $ mu$M. In a primary infection, the higher establishment and higher worm numbers one-month post-infection in the resistant parasites compared to the stock parasites occurred only in the drug-selected lines. Changes in these traits were attributed to the drug selection regime. In contrast, both drug-selected lines and passaged lines showed a faster rate of development and higher early egg production compared with the stock parasites; these changes were attributed to the passage procedure that presumably acted as a selective force on early life history traits. In immunized hosts, changes in several traits that o
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Wa, Kasongo Kasongo. "Development and in vitro evaluation of a clobetasol 17-propionate topical cream formulation." Thesis, Rhodes University, 2007. http://hdl.handle.net/10962/d1003277.
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One of the primary contributing factors to the escalating costs of health care is the high cost of innovator pharmaceutical products. As a consequence, health authorities in various countries and in particular in the developing world have identified generic prescribing and generic substitution as possible strategies to contain the escalating costs of health care provision. There is therefore a need for formulation scientists in developing countries to invest more time in the research and development of generic formulations. Clobetasol 17-propionate (CP) generic cream formulations containing 0.05% w/w of the drug were manufactured and characterized using in vitro testing. Formulation development studies were preceded by the development and validation of an RP-HPLC with UV detection for the quantitation and characterization of CP in innovator and generic cream formulations during formulation development and assessment studies. Furthermore the in vitro release ates of CP release from innovator and generic cream formulations were monitored using a validated in vitro release test method developed in these studies. The formulation of CP cream products was accomplished using a variety of commercially available mixed primary emulsifiers, such as Estol® 1474, Ritapro® 200, Emulcire® 61 WL and Gelot® 64. Successful formulations were selected based on their ability to remain physically stable immediately after manufacture and for 24 hours after storage at room temperature (22°C). Estol® 1474 was found to produce an unstable cream and was therefore not investigated further. The other three emulgents produced stable creams, but only the in vitro release profile of CP from a cream manufactured to contain Gelot® 64 was found to be statistically similar to that of the innovator formulation. Therefore the cream containing Gelot® 64 was selected as the most appropriate prototype generic cream formulation and was characterized in vitro in terms of CP content, viscosity, pH and in vitro release rate. Data generated from these studies were compared to those of the innovator product, Dermovate® cream, using statistical methods. The CP content, pH and in vitro release rate data of the CP formulation were similar to those of the innovator product, however the intrinsic viscosity of Dermovate® cream was almost three (3) times greater than the intrinsic viscosity of the test formulation developed using Gelot® 64. The CP cream formulation developed in these studies was stored for 4 weeks at 40 ± 2°C and 25 ± 5% RH in an incubator and the formulation was found to be stable. A formulation has been developed and assessed and found to be suitable for use as a topical semi-solid dosage form for CP.
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Lloyd, Edward John, and mikewood@deakin edu au. "A common structural basis for central nervous system drug design." Deakin University. School of Biological Sciences, 1986. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20050902.115505.
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The main theme of this thesis is that there is a common structural basis for drugs acting on the central nervous system (CNS), and that this concept may be used to design new CNS-active drugs which have greater specificity and hence less side-effects.
To develop these ideas, the biological basis of how drugs modify CMS neurotransmission is described, and illustrated using dopaminergic pathways. An account is then given of the use of physicochemical concepts in contemporary drug design. The complete conformational analysis of several antipsychotic drugs is used to illustrate some of these techniques in the development of a model for antipsychotic drug action.
After reviewing current structure-activity studies in several classes of CNS drugs (antipsychotics, anti-depressants, stimulants, hal1ucinogens, anticonvulsants and analgesics), a hypothesis for a common structural basis of CNS drug action is proposed- This is based on a topographical comparison of the X-ray structures of eight representative CNS-active drugs, and consists of three parts: 1.there is a common structural basis for the activity of many different CNS-active drug classes; 2. an aromatic ring and a nitrogen atom are the primary binding groups whose topographical arrangement is fundamental to the activity of these drug classes;
3. the nature and placement of secondary binding
determines different classes of CNS drug activity. A four-Point model for this common structural basis is then defined using 14- CNS-active drug structures that include the original eight used in proposing the hypothesis. The coordinates of this model are: R1 (0. 3.5, 0), R2 (0, -3.5, O), N (4.8. -0.3, 1.4), and R3 (6.3, 1.3, 0), where R1 and R2 represent the point locations of a hydrophobic interaction of the common aromatic ring with a receptor, and R3 locates the receptor point for a hydrogen bond involving the common nitrogen, N. Extended structures were used to define the receptor points R1, R2 and R3, and the complete conformational space of each of the 14 molecules was considered.
It is then shoun that the model may be used to predict whether a given structure is likely to show CNS activity: a search over 1,000 entries in the current Merck Index shows a high probability (82%) of CNS activity in compounds fitting the structural model.
Analysis of CNS neurotransmitters and neuropeptides shows that these fit the common model well. Based on the available evidence supporting chemical evolution, protein evolution, and the evolution of neurotransmitter functions, it is surmised that the aromatic ring/nitrogen atom pharmacophore proposed in the common model supports the idea of the evolution of CNS receptors and their neurotransmitters, possibly from an aromatic amine or acety1cho1ine acting as a primaeval communicating molecule.
The third point in the hypothesis trilogy is then addressed. The extensive conformation-activity analyses that have resulted in well-defined models for five separate CNS drug classes are used to map out the locations of secondary binding groups relative to the common model for anti-psychotics, antidepressants, analgesics, anticholinergics, and anticonvulsants. With this information, and knowledge derived from receptor-binding data, it is postulated that drugs having specified activity could be designed.
In order to generate novel structures having a high probability of CNS-activity, a process of drug design is described in which known CNS structures are superimposed topographically using the common model as a template. Atoms regarded as superfluous may be selectively deleted and the required secondary binding groups added in predicted locations to give novel structures.
It is concluded that this process provides the basis for the rational design of new lead compounds which could further be optimized for potent and specific CNS activity.
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Lynch, Catherine. "The effect of anti-epileptic drugs on the behaviour of the fetus." Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.579785.
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The rich behavioural repertoire of the fetus provides a means of assessing central nervous system integrity, and thus the well-being of the fetus. Pregnancy in women with epilepsy is associated with a higher risk of congenital malformation and long-term developmental delay. The cause of these risks is thought to be the anti-epileptic drugs that women with epilepsy continue to take during pregnancy to prevent seizures. This thesis, using fetal behaviour as a diagnostic tool, studied the effect of the anti-epileptic drugs; Carbamazepine, Lamotrigine and Valproate on the fetal behaviour. The spontaneous behaviour and the habituation response of the fetus were examined at 12- 15, 18-22, 31 and 37 weeks of gestation in two groups of mothers; those mothers with epilepsy taking anti-epileptic drugs and a control group of mothers not having epilepsy and thus not taking anti-epileptic drugs. Further analyses examined the effects of the specific drug; mothers were taking Carbamazepine, Lamotrigine or Valproate with a group of mothers not taking anti-epileptic drugs. There was a significant difference between the fetuses in the Carbamazepine group and the control group higher at 12-15 weeks gestation. Total activity was significantly higher in the Carbamazepine group compared with fetuses not exposed to anti-epileptic drugs. Mean mouth movement scores were significantly lower at 18-22 weeks in fetuses exposed to Carbamazepine. Habituation performance was significantly different for the fetuses exposed to Carbamazepine at 31 weeks gestation. The . fetuses exposed to Carbamazepine showed a poorer habituation performance. Postnatally children who had been exposed Valproate scored significantly lower in both the mental and psychomotor developmental index scores of the Bayleys scale of Infant Development than children who had not been exposed to anti-epileptic drugs. Anti-epileptic drugs were observed to affect the behaviour of the fetus, suggestive of an effect on the central nervous system.
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Yazid, Samia. "The effect of cromoglycate-like drugs on the glucocorticoid-annexin A1 system." Thesis, Queen Mary, University of London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511352.
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Krishnamoorthy, Mahesh Kumaar. "Effect of Retinal Permeability Variation on Pharmacokinetics of Drugs in the Eye." University of Cincinnati / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163578450.
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Meza, Benjamin. "The Effect of Cell Type on the Efficacy of CMV Antiviral Drugs." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1567.
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Until recently, all in vitro drug susceptibility assays of cytomegalovirus (CMV) were performed in clinically irrelevant fibroblast cells. This study sought to test if drug susceptibility was affected by cell type. MRC-5 embryonic lung fibroblasts and ARPE-19 retinal pigmented epithelial cells were infected with BADrUL131-Y4 epithelial/fibroblast tropic virus under serial concentrations of ganciclovir (GCV) or maribavir (MBV). Virus was quantified using plaque reduction, GFP fluorescence, and yield reduction. Both drugs performed less efficiently in ARPE-19 cells. A cell type effect was observed for both plaque reduction and yield reduction assays with implications for the treatment of CMV retinitis as well as other manifestations of CMV Disease that involve non-fibroblast cell types.
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Tremblay, Mélanie. "Kindling, drugs and decision-making : an exploration of the effect of anticonvulsant drugs and provoked seizures on a rat Gambling Task." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44938.
Full textAbstract:
Impulsivity is a major component of mania in bipolar disorder, and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are also observed in some patients with temporal lobe epilepsy (TLE), in which seizures originate in the amygdala and hippocampal formations, and incidence of pathological gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of bipolar disorder. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioural aspect targeted by these drugs. Patients with damage to the basolateral amygdala (BLA) also show deficits in decision-making, and rats with BLA lesions have shown such deficits in a variety of behavioural tasks. Few studies have looked at the effect of BLA stimulation on risky decision-making. This project first aimed at exploring the effect of the three anticonvulsant drugs currently also used as mood stabilisers- carbamazepine, valproate and lamotrigine- on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). We then investigated the effect of kindling of the BLA on this task, with the aim of antagonizing any behavioural effects with the anticonvulsant drugs. Thirty-two rats in total learned the rGT. Sixteen rats were used in the pharmacology study, and 16 were implanted unilaterally with a bipolar electrode into the BLA and stimulated twice daily until kindling had been established i.e. three class five seizures were observed. Carbamazepine appeared to slow processing speed, decreased premature responses and also blocked the pro-impulsive effect of amphetamine. Kindling increased choice of the small, but immediate reward option P1 and also increased premature responses. However, none of the changes observed were permanent and therefore, we could not assess the effect of carbamazepine on blocking the effect of kindling. Further studies looking at chronic administration of anticonvulsants, and the effect of kindling on acquisition of the rGT, would help us understand the neurobiological mechanisms underlying vulnerability to impairments in decision-making under uncertainty associated with TLE and other psychiatric disorders.
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Cader, Sarah. "Cognitive function in multiple sclerosis and its modulation by cholinergic drugs." Thesis, University of Oxford, 2005. http://ora.ox.ac.uk/objects/uuid:d07ad815-4fc6-43b7-96dc-97a2705d6c6a.
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In order to assess cognitive function in multiple sclerosis (MS) and the effect of cholinergic modulation, experiments were conducted using functional magnetic resonance imaging (fMRI) to assess the brain activation during cognitive tasks. A study comparing the processing of verbal working memory with an N-back task found that patients showed smaller increase in activation than healthy controls with greater task difficulty, suggesting a reduced functional reserve. Controls and patients showed differences of correlations between brain regions activated. Interactions between prefrontal regions may provide an adaptive mechanism that could limit clinical expression of the disease distinct from recruitment of novel processing regions. The effect of Rivastigmine on the cognitive processing in MS patients was tested in a longitudinal study, involving serial fMRI scans. Changes in the brain activation patterns were demonstrated with drug administration, without any changes in behavioural measures. Rivastigmine may act to increase the functioning of the normal neural network reducing the need for previously recruited compensatory mechanisms in MS patients. A study on healthy subjects examined the effect of cholinergic inhibition on cognitive processing and brain activation. Changes in functional activation due to Hyoscine during verbal working memory were found analogous to that in MS patients without any changes in behavioural measures. Processes that potentially impair brain cognitive function may recruit similar compensatory functional adaptive mechanisms. Studies on rats and MS patients explored the effect of Rivastigmine on the relationship of the BOLD fMRI signal with the underlying neural activity. Rivastigmine may be influencing the cortical excitability after direct cortical stimulation but showed only a small effect on the BOLD signal under more physiological neural activity. The neural activity in response to visual stimulation is slightly increased with Rivastigmine in MS patients, a change not detected with functional imaging. These studies suggest that changes in BOLD signal do represent sufficiently large changes of underlying neural activity in the presence of Rivastigmine. The relationship of damage in MS to measures of connectivity was studied using diffusion tensor imaging (DTI). Correlation was found between measures of connectivity and callosal size, a measure of fibre loss. The distribution of lesions was spatially correlated with changes in connectivity due to MS. Thus DTI could be utilized to explore the connectivity changes associated with MS, and the relationship with changes in functional activation.
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Ho, Yee-wa Eva, and 何綺華. "Effects of Ganoderma lucidum on rheumatoid synovial fibroblasts." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29489933.
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Brown, Michael Patrick. "Effect of Ototoxic Drugs on the Amphibian Auditory System: Injection of Gentamicin Sulfate into Anuran Otic Capsules and Recovery of Thresholds." PDXScholar, 1995. https://pdxscholar.library.pdx.edu/open_access_etds/4858.
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Hair cell trauma from aminoglycosides, which may lead to permanent loss of hair cells in mammals, was studied physiologically in frogs by measuring an auditory evoked potential (AEP) in Rana pipiens. The AEP was evaluated in order to measure threshold shift (TS) and recovery from TS after the administration of the aminoglycoside antibiotic, gentamicin. To obtain an AEP, chronic electrodes were implanted into the cranium near the cochlear nucleus. The frogs were then exposed to frequency-specific narrow band ~clicks" which included a single period 1 kHz sinewave, and a computer synthesized high frequency and low frequency click. Amphibians have two hearing organs, the amphibian and basilar papillae, sensitive to low (150-1500) and high (1500-2000) frequencies, respectively. The low (AP) and high (BP) frequency clicks were created to stimulate specifically the corresponding papillae. After normal thresholds were recorded for each frog, gentamicin sulfate, 200 μM, 300 μM, or 400 μM, was injected bilaterally into the otic capsules. Thresholds were recorded until the TS had disappeared, allowing the threshold recovery period to be measured. The injections of 200 μM yielded a 10 dB change in one animal and no change in two others. The injection of 300 μM into 10 frogs and 400 μM into 20 frogs yielded at least a 10 dB change in 60% and 93% of the frogs, respectively, with the concentration of 400 μM producing threshold shifts of 20 dB. Thus, the threshold shifts were dose-dependent. Recovery times varied between six and fourteen days. No apparent differences between thresholds for the high frequency click, low frequency click and sinewave clicks were observed.
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Abumansour, Hamza M. A. "Quantitative pharmacoproteomics investigation of anti-cancer drugs in mouse : development and optimisation of proteomics workflows for evaluating the effect of anti-cancer drugs on mouse liver." Thesis, University of Bradford, 2016. http://hdl.handle.net/10454/15724.
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Minimizing anti-cancer drug toxicity is a major challenge for the pharmaceutical industry. Toxicity is most frequently due to either the direct interaction of the drug on previously unidentified targets or its conversion to metabolites by drug metabolizing enzymes (e.g. CYP450 enzymes) that cause cellular, tissue or organ damage. Pharmacoproteomics is beginning to take a central role in studying changes in protein expression corresponding to drug administration, the results of which, inform about the mode of action, toxicity, and resistance in pre-clinical and clinical stages of drug development. The main aim of this research is to apply comparative proteomics studies on livers from male and female mice xenograft models treated with major anti-cancer drugs (5-flourouracil, paclitaxel, cisplatin, and doxorubicin) and CYP inducer, TCPOBOP, to investigate their effect on protein expression profiles (proteome). Within this thesis, an attention is paid to optimise a highly validated proteomics workflow for biomarker identification. Proteins were extracted from liver microsomes of mice treated in two separate sets; Set A – male (5-fluoruracil, doxorubicin, cisplatin and untreated) or Set B – female (5-fluoruracil, paclitaxel, TCPOBOP and untreated) using cryo-pulverization and sonication method. The extracts were digested with trypsin ii and the resulting peptides labelled with 4-plex iTRAQ reagents. The labelled peptides were subjected for separation in two-dimensions by iso-electric focusing (IEF) and RP-HPLC techniques before analysis by mass spectrometry and database searching for protein identification. Set A and Set B resulted in identification and quantification of 1146 and 1743 proteins, respectively. Moreover, Set A and Set B recovered 26 and 34 cytochrome P450 isoforms, respectively. The microsomal changes after drug treatments were quite similar. However, more changes were observed in the male set. Up-regulation of MUPs showed the greatest distinction in the protein expression patterns in the treated samples comparing to the untreated controls. In Set A, 5-fluoruracil and cisplatin increased the expression of three isoforms (MUP1, 2, and 6), whereas doxorubicin has increased the expression of four isoforms (MUP1, 2, 3, and 6). On the other side, only TCPOBOP in Set B has increased the expression of two isoforms (MUP1 and 6). Our findings showed that the expression of MUP, normally involved in binding and excretion of pheromones, have drug- and sex-specific differences. The mechanism and significance of MUP up-regulation are ambiguous. Therefore, the impact of each therapeutic agent on MUP and xenobiotic enzymes will be discussed.
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Maune, Jerene Mary 1953. "THE EFFECT OF CAFFEINE ON HEART RATE, RHYTHM AND BLOOD PRESSURE." Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/276372.
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Gregg, Amy B. "The immunological effects of antibiotic treatment and probiotic populations on oral tolerance in ova fed mice." Virtual Press, 2007. http://liblink.bsu.edu/uhtbin/catkey/1371839.
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Probiotics are a live microbial supplement that reside within the intestinal tract and are considered normal flora. The Balb/c mouse model was used to determine if the elimination of probiotics, general LAB species, by antibiotics plays a role in the breakdown of oral tolerance leading to the generation of an immune response to oral antigens. A mouse model was developed for in vivo research regarding probiotic populations and the effect on the induction of oral tolerance. The Balb/c mouse was used to determine if the mouse model had a colonized intestinal tract with probiotics followed by a reduction of probiotics that was done with orally administered antibiotics. After the reduction of probiotics, mice were fed oral antigen, ovalbumin, to determine that an immune response was not shown with oral antigen alone. After the mouse model was set up, mice were then fed oral antigen and then stimulated with immunizations to study the induction of oral tolerance and the possible effect of the absence of probiotics. The results indicated that mice with reduced probiotics and fed with oral antigen alone do not show an immune response. In contrast, mice fed with oral antigen followed by immunization indicate a higher OVA-specific serum IgG. This is evidence that correlates with clinical findings in disease states such as Crohn's Disease and Irritable Bowel Syndrome (IBD).Department of Biology
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Balaños, Guzman Carlos Alberto. "The effects of the kappa agonist U-50,488 on morphine-induced place preference conditioning and Fos immunoreactivity in the preweanling and periadolescent rat." CSUSB ScholarWorks, 1995. https://scholarworks.lib.csusb.edu/etd-project/1074.
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The effects of the kappa opioid agonist U-50,488 on morphine-induced condtioned place preference (CPP), locomotor activity and Fos immunoreactivity and assessed in 10-, 17- and 35-day old rats. It was predicted that kappa agonist treatment would block the unconditioned and conditioned behaviors produced by morhine (a mu opioid receptor agonist).