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1
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.
2
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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Ramadan, Waile Rushing Ann E. Hartberg W. Keith. "The protective effect of [alpha]-lipoic acid in doxorubicin induced cardiotoxicity in rats." Waco, Tex. : Baylor University, 2008. http://hdl.handle.net/2104/5218.
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Li, Y. M. J. "An in-vivo study of the anti-arrhythmic and electrophysiological effects of amiodarone, lignocaine and penticainide (CM7857) in the rat." Thesis, De Montfort University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233821.
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Huang, Yi Fei. "Myocardial pharmacokinetics and pharmacodynamics in the sheep /." Title page, contents and abstract only, 1991. http://web4.library.adelaide.edu.au/theses/09PH/09phh8742.pdf.
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Thesis (Ph. D.)--University of Adelaide, Dept. of Anaesthesia and Intensive Care, 1992.Accompanying diskette contains data of Chapters 3, 4, 5, 7, 8 and 9 (ASCII). Includes bibliographical references (leaves 177-207).
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Ritchie, Rebecca Helen. "Acute haemodynamic effects of three cardioactive agents: metoprolol, sotalol and milrinone : influence of myocardial content and systolic interval /." Title page, table of contents and summary only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09phr611.pdf.
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Shubat, Pamela Jane. "Monocrotaline toxicity and pulmonary arteries." Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184533.
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Monocrotaline is a pyrrolizidine alkaloid found in plants implicated in livestock and human poisoning. Laboratory rats given monocrotaline develop pulmonary hypertension and right heart hypertrophy in the weeks following administration of the chemical. Lung weight increases and right heart hypertrophy correlate with increased pulmonary artery pressure. Rats which consumed monocrotaline drinking water (20 mg/l) for only 4 days developed significant increases in lung and heart weights 14 days after exposure began. This exposure was equivalent to a dose of 15 mg/kg. Other treatment combinations of time (0-10 days exposure) and monocrotaline concentration (5-60 mg/l in drinking water) were tested. The accumulative dose calculated for each of the treatment combinations which produced toxicity was in the range of 15 to 20 mg/kg. Monocrotaline injury appears to be cumulative, but organ weight increases reverse once exposure is stopped. As pulmonary hypertension develops and pulmonary arteries hypertrophy, the force with which isolated pulmonary artery segments contract decreases. This is a loss of efficacy rather than potency to the contracting agents KCl, norepinephrine, and 5-hydroxytryptamine. Relaxation of arteries under conditions of potassium-return (a measure of Na⁺/K⁺ ATPase activity) was also altered by monocrotaline treatment. In vivo monocrotaline treatment had little effect on the force of K⁺-return relaxation. However, the rate at which arteries relaxed was significantly decreased following 4 days ingestion of monocrotaline drinking water (20 mg/l). In vitro ouabain treatment and endothelial injury also decreased the rate of K⁺-return relaxation. Another Na⁺/K⁺ ATPase activity, ⁸⁶Rb⁺ uptake, was decreased following monocrotaline treatment only when 5-hydroxytryptamine was present and only uptake associated with the endothelium was affected. These studies utilized a very low exposure to monocrotaline (4 days ingestion of 20 mg/l monocrotaline drinking water or 15 mg/kg) to produce toxicity in rats. Monocrotaline-induced toxicity measured 20 days after treatment included right heart and lung hypertrophy and decreased contractions of isolated pulmonary arteries. Monocrotaline treatment decreased the rate of Na⁺/K⁺ ATPase-dependent relaxation of isolated pulmonary arteries 4 days after treatment began.
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Rossouw, Ellen. "The effect of androgenic anabolic steroids on the susceptibility of the rat heart to ischaemia and reperfusion injury." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/53105.
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Thesis (MSc)--University of Stellenbosch, 2002.ENGLISH ABSTRACT: Background: Athletes use androgenic anabolic steroids (AAS) to enhance their physical performance. The abuse of AAS is however associated with a host of side effects including sudden death due to cardiac arrest. The use of AAS leads to myocardial hypertrophy, which possibly makes the heart more prone to ischaemia/reperfusion injury, since it often develops in the absence of proper vasculature development. Chronic AAS use also disrupts myocardial p-adrenoreceptor function and possibly cAMP, signalling in the heart. Drugs increasing cAMP and decreasing cGMP levels in the ischaemic myocardium exacerbate myocardial ischaemia/reperfusion injury. We also know that AAS causes coronary artery disease secondary to the deleterious alteration of lipid profiles by increasing the LOL cholesterol and decreasing the HOLcholesterol levels. AAS treatment may increase systemic TNFa levels by stimulating lymphocyte TNFa secretion that has been implicated in the depression of myocardial function, myocardial hypertrophy and the worsening of ischaemia/reperfsuion injury. Aims: To determine whether chronic AAS treatment in trained and untrained rats influences: 1) heart function and susceptibility to ischaemia/reperfusion injury, 2) myocardial cyclic nucleotide levels (cAMP and cGMP) and 3) myocardial TNFa levels. Material and methods: Male Sprague-Dawley rats (n=100) were divided into 4 groups: sedentary vehicle (placebo) treated group, sedentary AAS treated group, exercise vehicle (placebo) treated group, and exercise AAS treated group. Steroid treated animals received an intramuscular injection of nandrolone laureate (0.375 mg/kg) once a week, for six weeks. Training consisted of swim sessions 6 days a week for 6 weeks. Swim time was incrementally increased up to a maximum of 50 minutes a day. For biometric parameters heart weight and body weight were documented. Hearts were mounted on a l.anqendorff perfusion apparatus and left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF) was monitored. The hearts were subjected to a period of 20 minutes of global ischaemia, followed by 30 minutes of reperfusion. Functional parameters was again monitored and documented. For biochemical analysis, blood was collected for the determination of serum lipid levels and myocardial tissue samples were collected before, during and after ischaemia for the determination of myocardial TNFa, cGMP and cAMP levels and p38 activity. Conclusions: Results obtained would suggest that AAS exacerbate exercise induced myocardial hypertrophy. It also prevents the exercise-induced improvement in cardiac function. AAS use reduces reperfusion function in treated hearts, which may suggest that AAS exacerbates ischaemie and reperfusion injury. Furthermore it was seen that AAS elevates basal (preischaemie) cyclic nucleotide levels and basal (pre-ischaemic) as well as reperfusion TNFa levels. This may also contribute to the exacerbation of ischaemic and reperfusion injury.
AFRIKAANSE OPSOMMING: Agtergrond: Androgeniese anaboliese steroïede (AAS) word dikwels deur atlete gebruik om sportprestasie te verbeter. Die misbruik van AAS het egter talle newe effekte, insluitende skielike dood wat gewoonlik toegeskryf word aan hartaanvalle. Die gebruik van AAS lei onder andere tot miokardiale hipertrofie wat opsigself, as gevolg van ontoereikende vaskulêre ontwikkeling tydens die ontwikkeling van hipertrofie, die hart nog meer vatbaar vir isgemie/herperfusie skade maak. Kroniese AAS toediening versteur miokardiale beta-adtenoresepter funksie en moontlik die tweede boodskapper, sAMP, seintransduksie in die hart. Ons weet ook dat AAS koronêre hartvatsiektes veroorsaak. Laasgenoemde is sekondêr tot die nadelige lipiedprofiel verandering, wat 'n verhoging in LDL-C en 'n verlaging in HDL-C insluit. Middels wat miokardiale sAMP vlakke verhoog en sGMP vlakke in die isgemiese miokardium verlaag, vererger miokardiale isgemie/herperfusie skade. AAS behandeling kan moontlik ook sistemiese TNFa vlakke verhoog deur limfosiet TNFa sekresie te stimuleer. Die verhoogde TNFa vlakke word verbind aan die onderdrukking van miokardiale funksie, miokardiale hipertrofie en die verergering van isgemie/herperfusie skade. Doelwitte: Die doelwitte van die studie was om te bepaal of kroniese AAS toediening in geoefende en ongeoefende rotte 1) hartfunksie en die hart se vatbaarheid vir isgemie/herperfusie skade beïnvloed, 2) miokardiale sikliese nukleotiedvlakke (sAMP en sGMP) beïnvloed en 3) miokardiale TNFa-vlakke beïnvloed. Materiale en metodes: Manlike Sprague-Dawley rotte (n=100) is gebruik en in 4 groepe verdeel: 'n ongeoefende placebo groep (kontrole); 'n ongeoefende steroïedbehandelde groep; 'n geoefende placebo groep (kontrole) en 'n geoefende steroïedbehandelde groep. Steroïed behandelde diere het 'n intramuskulêre nandroloon lauraat inspuiting (0.375 mg/kg) een keer per week vir ses weke ontvang. Die oefenprogram het bestaan uit ses swemsessies 'n week vir ses weke. Die swemtyd is geleidelik weekliks verhoog tot by 'n maksimum tyd 50 min. Die waterbadtemperatuur is tussen 30 - 32 oe gehandhaaf. Vir biometriese parameters is hartgewig en liggaamsgewig genoteer. Harte is op 'n Langendorff perfusie apparaat gemonteer en linker ventrikulêre ontwikkelde druk (LVOD), koronêre vloei (KV) en harttempo (HT) is genoteer. Die harte is vervolgens blootgestel aan 20 minute van globale isgemie gevolg deur 'n 30 minute herperfusieperiode. LVOD, KV en HT is weer eens noteer. Vir biochemiese doeleindes is bloed voor perfusie versamelom serum lipied vlakke te bepaal. Miokardiale weefsel is versamel voor, tydens en na isgemie vir die bepaling van TNFa, cGMP en AMP vlakke asook p38 aktiwiteit. Gevolgtrekkings: Na aanleiding van resultate verkry wil dit voorkom asof die gebruik van steroïde oefeningsgeïnduseerde miokardiale hipertrofie vererger. Dit verhoed ook oefeningsgeïnduseerde verbetering in miokardiale funksie. AAS lei tot 'n verlaagde herperfusiefunksie in behandelde harte, wat dalk mag dui op MS verergering van isgemie en herperfusie skade. Verder was daar ook waargeneem dat MS basale (pre-isgemiese) sikliese nukleotiedvlakke en basale TNFa-vlakke sowel as herperfusie TNFa vlakke verhoog. Die verhoging in TNF-a vlakke mag dus moontlik ook bydra tot die verergering van isgemie- en herperfusieskade.
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Leigh, Felicity Suzanne Marshall. "The effects of diet, anorectic drugs and caffeine on various cardiovascular parameters in the rat." Thesis, University of Bath, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382595.
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Kalis, Joni Kathryn. "THE EFFECT OF BETA-ADRENERGIC BLOCKADE ON THE DRIFT IN OXYGEN CONSUMPTION WITH PROLONGED EXERCISE." Thesis, The University of Arizona, 1985. http://hdl.handle.net/10150/292014.
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Santos, Priscila Portugal [UNESP]. "Influência da suplementação de dieta com diferentes doses de vitamina D sobre variáveis cardíacas em ratos." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/92124.
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santos_pp_me_botfm.pdf: 349987 bytes, checksum: 913fc9a75063c45bd784ef00c6dc221f (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A frequência de hipovitaminose D é alta na população. A deficiência de vitamina D tem sido considerada problema de saúde pública no Brasil e no mundo. Além disso, a deficiência dessa vitamina está associada com o aumento do risco de várias doenças crônicas. Assim, está ocorrendo uso indiscriminado de vitamina D sem conhecer ao certo seus efeitos adversos. Estudos mostraram que essa vitamina é importante para o desenvolvimento e funcionamento adequado do coração. A deficiência de vitamina D provoca remodelação cardíaca enquanto que a suplementação de vitamina D, em modelos de agressão, atenua a remodelação. Porém pouco se sabe sobre sua influência no coração normal. O objetivo foi verificar se a suplementação com diferentes doses de vitamina D3 na dieta promove remodelação cardíaca com alterações na estrutura, na função, no metabolismo energético e nos moduladores inflamatórios do coração normal de ratos Wistar. Para isso foram utilizados 86 ratos machos, alocados em quatro grupos: Controle (C, n=21) recebeu dieta padrão; 3D (n=22), 5D (n=22) e 10D (n=21) receberam 3.000, 5.000 e 10.000 UI de colicalciferol/kg de dieta respectivamente. Após dois meses foi realizada a pressão arterial caudal e o estudo ecocardiográfico. Os animais foram eutanasiados, o soro e o ventrículo esquerdo foram utilizados para análises bioquímicas. Para análise estatística foi realizado ANOVA de 1 via e pós teste de Tukey ou Kruskal Wallis e pós teste de Dunn. Para avaliar a resposta dose dependente foi utilizado o teste de tendência (correlação de Spearman). As concentrações séricos de cálcio e fósforo foram maiores no grupo 5D e 10D em relação ao C. A pressão caudal foi maior nos grupos 3D e 10D em relação ao C e apresentou aumento dose dependente. A concentração sérica de 25 (OH) D3 foi maior no grupo 5D em relação aos outros grupos e foi maior...
Frequency of hypovitaminosis D in population is high and vitamin D deficiency has been considered a public health problem. Moreover, Vitamin D deficiency is associated with increased risk of many chronic diseases. Thus, it is widespread use of vitamin D without knowing its adverse effects. Studies have shown that this vitamin is important for cardiac development and functioning. Vitamin D deficiency results in cardiac remodeling and vitamin D supplementation in cardiac aggression models attenuates cardiac remodeling. However, influence of vitamin D supplementation in normal rats is not completed known. The aim of this study was to evaluate whether supplementation with vitamin D3 results in cardiac remodeling with changes in structure, function, energy metabolism and inflammatory mediators in the heart of normal rats. We used 86 male rats allocated into four groups: control (C, n = 11) received standard diet; 3D (n = 12), 5D (n = 13) and 10D (n = 11) received 3000, 5000 and 10,000 IU of cholecalciferol / kg diet. After two months the animals were submitted to functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Tukey, the test Kruskal Wallis complemented by Dunn. To evaluate the dose response was used the Spearman correlation. Serum calcium and phosphorus were higher in the 5D and 10D in relation to the group C. The blood pressure was higher in the groups 3D and 10D in relation to the group C. The increase in blood pressure was dose dependent. Serum 25 (OH) D3 was higher in the group 5D in relation to the other groups and it was higher in the group 10D in relation to the group C. There were no differences in echocardiographic variables of morphology and function. The activity of the enzyme β hydroxyacyl coenzyme A dehydrogenase was smaller in the groups 5D and 10D in relation to other groups... (Complete abstract click electronic access below)
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Azarbayjani, Faranak. "Common mechanism for teratogenicity of antiepileptic drugs : Drug-induced embryonic arrhythmia and hypoxia-reoxygenation damage." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5065-2/.
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Persson, Kirstin Gracia. "In vivo effects of crinum macowanii on the rat cardiovascular system." Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_4721_1222073945.
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Crinum macowanii (C. macowanii) (Amaryllidacea) as authenticated by Mr. F. Weitz at the Herbarium, University of the Western cape, is widely used a traditional remedy and is thought to have therapeutic value (Fennell and van Staden 2001). The objective of this study was to determine the cardiovascular effects of the crude aqueous extract of Crinum macowanii on the rat and to determine the effect of pre-treatment drugs on Crinum macowanii in in vivo, anaesthetized normotensive, male Wistar rats (200-250 g.).
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Gharanei, A. M. "Investigation into the cardiotoxic effects of doxorubicin and strategies for cardioprotection." Thesis, Coventry University, 2013. http://curve.coventry.ac.uk/open/items/ad712004-828e-4d9a-8ddb-17951146d414/1.
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Doxorubicin is one of the most effective anti-cancer agents; however its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Mitochondrial function and integrity are crucial for cellular processes in general and play an important role during diseased development. These characteristics of the mitochondria make them the prime target for treatments for majority of diseases and in particular of the cardiovascular system. The mitochondria are also considered to play an integral role in the manifestation of the cardiotoxic effects of compounds such as doxorubicin. The current project is designed to investigate the cardiotoxic effects of doxorubicin at tissue, cellular and protein level. In addition, it is investigated whether the inhibition of the mitochondrial permeability transition pore (mPTP) with cyclosporin A (CsA) or the inhibition of mitochondrial fission with the mitochondrial division inhibitor (mdivi-1) protects against the detrimental effects of doxorubicin on cardiac function. We also investigated whether co-treatment of doxorubicin with either CsA or mdivi-1 has any negative interaction with the cytotoxicity of doxorubicin against cancer cells. Langendorff results indicated that doxorubicin caused a time dependent reduction in the haemodynamic function of the heart as well as causing an increase in the infarct size to risk ratio in both naïve conditions and in conditions of ischaemia and reperfusion. Detrimental effects of doxorubicin on cardiac function were abrogated by co-treatment of doxorubicin with CsA or mdivi-1 in naïve conditions and in conditions of ischaemia and reperfusion. Cell viability data of isolated cardiac myocytes revealed that doxorubicin caused a concentration dependant decrease in the viability of neonatal cardiac myocytes as well as causing a reduction in the time taken to depolarisation and hypercontracture under sustained oxidative stress, all of which were prevented when co-treated with either CsA or mdivi-1. Doxorubicin significantly elevated the levels of p-Akt, p-Erk, p-Drp1 and p-p53. Co-treatment with CsA prevented the increase in the levels of p-Akt and p-Erk caused by doxorubicin in both naïve and IR condition whereas mdivi-1 prevented the increase in the levels of p-Erk, p-Drp1 and p-p53 and caused further increase in the levels of p-Akt. Using sinusoidal muscle length change during contraction and relaxation, it is demonstrated that doxorubicin caused a decrease in the power output, peak force and force during shorting. Detrimental effects of doxorubicin on work-loop contraction were abrogated when doxorubicin was co-administered with CsA. To conclude, results demonstrated that doxorubicin caused cardiotoxicity at tissue, cellular and protein level in both naïve conditions and in conditions of ischaemia and reperfusion injury. In addition, it is shown that the inhibition of mitochondrial permeability transition pore with CsA or the inhibition of the mitochondrial fission with mdivi-1 protect against doxorubicin-induced toxicity without affecting its anti-cancer properties.
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Santos, Priscila Portugal. "Influência da suplementação de dieta com diferentes doses de vitamina D sobre variáveis cardíacas em ratos /." Botucatu : [s.n.], 2011. http://hdl.handle.net/11449/92124.
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Resumo: A frequência de hipovitaminose D é alta na população. A deficiência de vitamina D tem sido considerada problema de saúde pública no Brasil e no mundo. Além disso, a deficiência dessa vitamina está associada com o aumento do risco de várias doenças crônicas. Assim, está ocorrendo uso indiscriminado de vitamina D sem conhecer ao certo seus efeitos adversos. Estudos mostraram que essa vitamina é importante para o desenvolvimento e funcionamento adequado do coração. A deficiência de vitamina D provoca remodelação cardíaca enquanto que a suplementação de vitamina D, em modelos de agressão, atenua a remodelação. Porém pouco se sabe sobre sua influência no coração normal. O objetivo foi verificar se a suplementação com diferentes doses de vitamina D3 na dieta promove remodelação cardíaca com alterações na estrutura, na função, no metabolismo energético e nos moduladores inflamatórios do coração normal de ratos Wistar. Para isso foram utilizados 86 ratos machos, alocados em quatro grupos: Controle (C, n=21) recebeu dieta padrão; 3D (n=22), 5D (n=22) e 10D (n=21) receberam 3.000, 5.000 e 10.000 UI de colicalciferol/kg de dieta respectivamente. Após dois meses foi realizada a pressão arterial caudal e o estudo ecocardiográfico. Os animais foram eutanasiados, o soro e o ventrículo esquerdo foram utilizados para análises bioquímicas. Para análise estatística foi realizado ANOVA de 1 via e pós teste de Tukey ou Kruskal Wallis e pós teste de Dunn. Para avaliar a resposta dose dependente foi utilizado o teste de tendência (correlação de Spearman). As concentrações séricos de cálcio e fósforo foram maiores no grupo 5D e 10D em relação ao C. A pressão caudal foi maior nos grupos 3D e 10D em relação ao C e apresentou aumento dose dependente. A concentração sérica de 25 (OH) D3 foi maior no grupo 5D em relação aos outros grupos e foi maior... (Resumo completo, clicar acesso eletrônico abaixo)Abstract: Frequency of hypovitaminosis D in population is high and vitamin D deficiency has been considered a public health problem. Moreover, Vitamin D deficiency is associated with increased risk of many chronic diseases. Thus, it is widespread use of vitamin D without knowing its adverse effects. Studies have shown that this vitamin is important for cardiac development and functioning. Vitamin D deficiency results in cardiac remodeling and vitamin D supplementation in cardiac aggression models attenuates cardiac remodeling. However, influence of vitamin D supplementation in normal rats is not completed known. The aim of this study was to evaluate whether supplementation with vitamin D3 results in cardiac remodeling with changes in structure, function, energy metabolism and inflammatory mediators in the heart of normal rats. We used 86 male rats allocated into four groups: control (C, n = 11) received standard diet; 3D (n = 12), 5D (n = 13) and 10D (n = 11) received 3000, 5000 and 10,000 IU of cholecalciferol / kg diet. After two months the animals were submitted to functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Tukey, the test Kruskal Wallis complemented by Dunn. To evaluate the dose response was used the Spearman correlation. Serum calcium and phosphorus were higher in the 5D and 10D in relation to the group C. The blood pressure was higher in the groups 3D and 10D in relation to the group C. The increase in blood pressure was dose dependent. Serum 25 (OH) D3 was higher in the group 5D in relation to the other groups and it was higher in the group 10D in relation to the group C. There were no differences in echocardiographic variables of morphology and function. The activity of the enzyme β hydroxyacyl coenzyme A dehydrogenase was smaller in the groups 5D and 10D in relation to other groups... (Complete abstract click electronic access below)
Orientador: Sérgio Alberto Rupp de Paiva
Coorientador: Leonardo A. M. Zornoff
Banca: Marcelo Macedo Rogero
Banca: Paula Schmidt Azevedo Gaiola
Mestre
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Komulainen, S. (Silja). "Effect of antihypertensive drugs on blood pressure during exposure to cold:experimental study in normotensive and hypertensive subjects." Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514286131.
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Abstract The aim of the present study was to describe the effects of different types of cold exposures on blood pressure (BP) and heart rate (HR) and to test how these cold-induced effects are modulated by antihypertensive drugs representing different kind of mechanisms of action. The tested drugs represented the following antihypertensive drug subgroups: metoprolol from beta-blocking agents, carvedilol from alfa- and beta-blocking agents, lisinopril from angiotensin converting enzyme inhibitors, eprosartan from angiotensin II antagonists, amlodipine from calcium channel blockers and hydrochlorothiazide from diuretics. The main outcome measures were the levels and changes in systolic (SBP) and diastolic blood pressure (DBP) and HR before, during and after cold exposure. The normotensive and mildly hypertensive subjects were exposed either to –15°C for 15 minutes (with winter clothing), 5°C for 45 minutes (minimal clothing) or to a cold pressor test (CPT). Before measurements at –15°C, metoprolol, carvedilol, lisinopril, eprosartan, hydrochlorothiazide or placebo were given for a week in a double-blind and crossover manner. In one test procedure (5°C and CPT) the test subjects ingested amlodipine for three days or were without drug ingestion before the tests in a crossover manner. Both SBP and DBP were markedly increased by all types of cold exposure. Cold-induced rises of SBP/DBP were higher during the exposure to 5°C and –15°C (19–35/20–24 mmHg) than during CPT (13/16 mmHg). Metoprolol, carvedilol, lisinopril, eprosartan and amlodipine decreased the level of BP during the exposure to 5°C and –15°C compared to placebo or no drug. The antihypertensive drugs, with dosages used in this study, did not affect the cold-induced rise of BP compared to no drug or placebo. HR increased during CPT, but decreased during exposure to 5°C and –15°C. Metoprolol and carvedilol decreased HR during exposure to –15°C compared to placebo. The present study demonstrates for the first time the effects of antihypertensive drugs on BP in hypertensive subjects exposed to cold similar to normal outdoor exposure in winter. Although the magnitude of the cold-induced rise in BP was not affected by the drugs, the drug-induced decrease in the level of BP kept the peak values in the cold closer to the recommended threshold limit valuesTiivistelmä Tutkimuksen tarkoituksena oli selvittää eri mekanismeilla vaikuttavien verenpainelääkkeiden vaikutusta verenpainevasteisiin ja sydämen lyöntitiheyteen kylmässä sekä verrata erilaisten kylmäaltistusten vaikutusta verenpaineeseen ja sydämen lyöntitiheyteen. Tutkitut lääkkeet edustivat seuraavia verenpainelääkeryhmiä: metoprololi beetasalpaajia, karvediloli yhdistettyjä alfa- ja beetasalpaajia, lisinopriili ACE-estäjiä, eprosartaani angiotensiini II antagonisteja, amlodipiini kalsiumestäjiä ja hydroklooritiatsidi diureetteja. Tärkeimmät mitatut vasteet olivat systolisen ja diastolisen verenpaineen ja sydämen lyöntitiheyden tasot ja muutokset ennen kylmäaltistusta, kylmäaltistuksen aikana ja sen jälkeen. Lisäksi mitattiin lämpötilavasteita ja tuntemuksia. Normo- ja hypertensiiviset koehenkilöt altistettiin joko –15°C:seen 15 minuutin ajaksi (talvivaatetuksessa), 5°C:seen 45 minuutin ajaksi (minimaalisella vaatetuksella) tai tehtiin ns. käden kylmävesitesti (CPT). Testisarjoissa (–15°C) metoprololi, karvediloli, lisinopriili, eprosartaani ja hydroklooritiatsidi tai plasebo annettiin viikon ajan kaksoissokko- ja vaihtovuoromenetelmällä. Yhdessä testisarjassa (5°C ja CPT) koehenkilöt ottivat amlodipiinia 3 päivän ajan tai olivat ilman lääkettä ennen testikertoja vaihtovuoroisessa järjestyksessä. Kaikki kylmäaltistustyypit nostivat merkittävästi sekä systolista että diastolista verenpainetta. Systolisen ja diastolisen verenpaineen nousu oli korkeampi koko kehon kylmäaltistuksissa (5°C tai –15°C) (19–35/20–24 mmHg) kuin ns. kylmävesitestissä (13/16 mmHg). Metoprololi, karvediloli, lisinopriili, eprosartaani ja amlodipiini laskivat verenpaineen tasoja koko kehon kylmäaltistuksessa verrattuna plaseboon. Yksikään verenpainelääkkeistä ei vaikuttanut merkittävästi kylmän aiheuttamaan verenpaineen nousuun verrattuna tutkimuskertaan ilman lääkettä tai plaseboon. Sydämen lyöntitiheys nousi ns. kylmävesitestin aikana, mutta laski koko kehon kylmäaltistuksissa (5°C ja –15°C). Metoprololi ja karvediloli laskivat sydämen lyöntiheyttä kylmäaltistuksessa (–15°C) verrattuna plaseboon. Tämä tutkimus kuvaa ensimmäistä kertaa, kuinka verenpainelääkkeet vaikuttavat verenpainetasoihin ja -vasteisiin kylmäaltistuksessa, joka simuloi tyypillisiä ulko-olosuhteita talvella. Vaikka lääkkeet eivät estäneet kylmän aiheuttamaa verenpaineen nousua, ne laskivat verenpaineen tasoa, jolloin verenpaine pysyi kylmässäkin lähempänä suositusrajoja
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Arstall, Margaret Anne. "Studies in myocardial ischaemia and infarction : effects of N-acetylcysteine on oxidative stress and myocardial salvage /." Title page, contents and summary only, 1995. http://web4.library.adelaide.edu.au/theses/09PH/09pha783.pdf.
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Mattern, Janet. "Muscarinic Receptor Modulation of the Phospholipid Effect in Cardiac Myocytes." Thesis, North Texas State University, 1986. https://digital.library.unt.edu/ark:/67531/metadc500469/.
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The muscarinic agonist carbachol stimulates a rapid increase in ^32Pi incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI) in calcium tolerant myocytes prepared from heart tissue. The density of muscarinic receptors, determined by [^3H]-QNB binding, is greater in the atria than in the ventricles. 250 uM carbachol decreased specific [^3H]-QNB binding to muscarinic receptors on myocyte membranes by fifty percent. Trifluoperazine, also a phospholipase C inhibitor, inhibited the carbachol stimulated increase in ^32Pi incorporation into PA and PI and did not interfere with muscarinic receptor binding. Therefore, isolated canine myocytes provide a suitable model system to further study the muscarinic receptor stimulated phospholipid effect, and its role in mediating biochemical processes and physiological function in the heart.
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Badrian, Bahareh. "Evaluation of the consequences of ERK and STAT3 activation in the heart." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2006. http://theses.library.uwa.edu.au/adt-WU2007.0027.
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[Truncated abstract] The enlargement of the heart, also known as myocardial hypertrophy, is thought to be a compensatory process that maintains the mechanical function of the heart in response to stress factors such as pressure or volume overload. Although this process is initially compensatory, it frequently results in heart failure and death. Cardiac hypertrophy is a complex process involving changes in the individual cardiac muscle cells, cardiac myocytes. As well as the morphological changes that result from hypertrophy, there are molecular changes within each cell that regulate the hypertrophic process. These molecular changes involve many different pathways within the cardiac myocytes and remain poorly understood . . . Both STAT3α and β overexpression resulted in the upregulation of the VEGF, MnSOD and SOCS-3 genes. This indicates that in the heart, STAT3β is able to activate the gene expression of these genes in a similar manner to STAT3α. However, STAT3α or β activation alone is not enough to induce cardiac hypertrophy. In conclusion, the results presented in this thesis determined a novel role for ERK in the induction of cell death in the heart and revealed many changes in cardiac gene expression following ERK activation. These genes may be the mediators of ERK responses and their identification provides valuable information and direction for further research in this area. One consequence of ERK activation was the negative regulation of the STAT3 pathway. Further investigation revealed for the first time that the STAT3 proteins themselves may not be involved in the induction of cardiac hypertrophy and that STAT3β, initially thought to be a transcriptional repressor, can induce the expression of genes that are known to be activated by STAT3α in the heart. Therefore, these results help to better understand the roles of these two signalling pathways in the heart.
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Davidson, Melissa Anne. "A Pharmacovigilance Approach for Assessing Cardiovascular, Osteological, and Carcinogenic Risk Associated with Thiazolidinedione Drugs Used in the Treatment of Type 2 Diabetes Mellitus." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38062.
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Diabetes is a chronic and debilitating disease that affects nearly half a billion people worldwide with the vast majority of diabetics suffering from Type 2 diabetes mellitus (T2DM), a disease characterized by insulin insensitivity that often requires pharmacotherapy to effectively maintain target blood sugar levels. The thiazolidinedione (TZD) class of drugs consists of oral hypoglycaemic agents used alone or in combination with other antidiabetic drugs to treat T2DM. The drugs within this class, which include rosiglitazone and pioglitazone, were originally heralded as providing novel first and second-line treatment of T2DM with glycaemic control and physiological effects comparable to, and in some cases, better than, first-line treatments such as metformin. However, over time they have also been associated with adverse cardiovascular, osteological, and carcinogenic effects in some, but not all clinical trials, observational studies, and meta-analyses. Given the conflicting evidence to date on the safety of TZD drugs, their role in the treatment of T2DM continues to be debated and epidemiological gaps remain. The objectives of this doctoral research are fourfold: 1) to conduct an in-depth review of the epidemiology of TZD pharmacotherapy including pharmacokinetics and modes of action, the results of previous studies investigating health risks and benefits associated with TZD treatment, and new and future uses for this class of drugs; 2) to determine whether diabetic patients treated with TZDs are at increased risk of adverse cardiovascular outcomes; 3) to assess whether TZD pharmacotherapy is associated with an increased risk of bone fractures and whether risks differ depending on fracture site and patient sex; and, 4) to investigate associations between TZD use and risk of bladder cancer. Specific research questions were investigated using nested case-control analyses designed to capture incident users of antidiabetic drugs and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records from more than 480 contributing hospitals throughout the United States. Findings from this work are reported in a series of manuscripts, including a published review paper. Key findings include: 1) TZD use was associated with an increased risk of incident myocardial infarction and congestive heart failure compared to never use of TZD drugs with a trend towards a potential early treatment effect within the first year of exposure to pioglitazone; 2) TZD use was associated with an increased risk of closed bone fractures among Type 2 diabetics with use of pioglitazone or rosiglitazone associated with an increased risk across multiple fracture sites in women, but only rosiglitazone use in men and only at peripheral fracture sites; 3) use of either pioglitazone or rosiglitazone were associated with an increased risk of incident bladder cancer compared to never users, however, a low number of bladder cancer cases resulted in underpowered analyses; and, 4) insulin use in a hospital setting may replace a patient's normal course of antidiabetic therapy which, when combined with other potential sources of bias in traditional nested case-control studies using hospital-based data, may lead to overestimation or underestimation of adverse health risks associated with non-insulin antidiabetic therapies. Although these findings warrant replication, the results of the research contained within this dissertation suggest that caution should be exercised when prescribing diabetic patients TZD drugs if they have cardiovascular, osteological, or carcinogenic risk factors. Additional pharmacovigilance studies should also continue to strive to better understand the health risks related to TZD therapy, especially as new therapeutic roles for TZDs in the prevention and treatment of some cancers, inflammatory diseases, and other conditions in non-diabetic populations are being explored.
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Branco, Klébia Magalhães Pereira Castello. "Análise clínica evolutiva do uso do tacrolimus como droga imunossupressora em transplante cardíaco pediátrico." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-24052011-163915/.
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O Tacrolimus é uma potente droga imunossupressora introduzida no transplante cardíaco no início da década de 90. Pacientes com rejeição refratária ou intolerância à ciclosporina podem responder à terapia de resgate com o tacrolimus. Os objetivos deste estudo foram: avaliar a evolução clínica das crianças submetidas ao transplante cardíaco que necessitaram da conversão de ciclosporina para tacrolimus por rejeição refratária, tardia ou efeitos adversos de difícil controle; avaliar a incidência de rejeição após a conversão para o tacrolimus e comparar a sobrevida dos pacientes em uso de tacrolimus e ciclosporina. Realizou-se estudo coorte, observacional, prospectivo, em 28 crianças submetidas ao transplante cardíaco no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e que foram submetidas à conversão da ciclosporina ao tacrolimus, no período de julho de 1999 a dezembro de 2009. Avaliou-se a incidência de episódios de rejeição e a sobrevida após a conversão. Realizou-se, também, a comparação entre os pacientes em uso de tacrolimus e os pacientes que permaneceram em uso de ciclosporina submetidos ao transplante cardíaco no mesmo período. A idade média no momento do transplante foi de 5,3 anos, e no momento da conversão de 8,2 anos. As causas de conversão foram efeitos adversos em 50% dos pacientes, rejeição tardia em 32% e rejeição refratária em 18%. O tempo médio de conversão e seguimento foram 36 meses e 74 meses, respectivamente. Observou-se resolução completa dos episódios de rejeição refratária e melhora dos efeitos adversos em todos os pacientes. A taxa de incidência (x100) de episódios de rejeição antes da conversão foi de 7,98 e após a conversão foi de 2,11 (p=0,0001). A taxa de episódios de infecção antes da conversão foi de 5,89 e após a conversão 4,18 (p=0,023). Pela análise das complicações pré e pós-conversão ao tacrolimus, não se evidenciou diferença estatisticamente significativa em relação a incidência de tumor, insuficiência renal, hipertensão arterial sistêmica, dislipidemia, litíase biliar, diabetes melito, anemia, alterações neurológicas, hirsutismo e hiperplasia gengival. Houve maior prevalência da doença vascular do enxerto após conversão para tacrolimus (p=0,004). Ao se comparar os pacientes com tacrolimus e os com ciclosporina, identificou-se diminuição significativa na taxa de incidência de episódios de rejeição (p=0,001), e na taxa de incidência de episódios de infecção (p=0,002), nos pacientes em uso de tacrolimus. Os pacientes convertidos ao tacrolimus apresentaram menor incidência de complicações neurológicas, hirsutismo e hiperplasia gengival, porém maior prevalência de anemia. Em relação à sobrevida, observou-se uma mortalidade de 25% nos pacientes em uso de tacrolimus, após um período médio de conversão de sessenta meses. Três óbitos foram secundários à rejeição, dos quais apenas um, no primeiro ano de transplante. Evidenciou-se menor sobrevida nos pacientes em uso de ciclosporina. O estudo clínico das crianças submetidas ao transplante cardíaco e que necessitaram de conversão do esquema de imunossupressão permitiu concluir que o tacrolimus foi eficaz como terapia de resgate para rejeição refratária e constitui opção terapêutica como droga imunossupressora de manutenção na faixa etária pediátricaTacrolimus is a potent calcineurin inhibitor that was introduced in heart transplantation therapy in the early 1990s. Organ transplant recipients with refractory rejection or intolerance to conventional immunosuppressant may respond to rescue therapy with tacrolimus. The aim of this study was to evaluate the clinical outcome of children undergoing heart transplantation who required conversion from a cyclosporine to a tacrolimus-based immunosuppressive regimen due to refractory rejection, late rejection or cyclosporine intolerance. We performed a prospective observational cohort study in 28 children who underwent cardiac transplantation at the Heart Institute (InCor) University of São Paulo Medical School and who required conversion from July 1999 to December 2009. The clinical outcome of the patients was evaluated after tacrolimus conversion. We also compared the patients on tacrolimus to the patients who remained on cyclosporine, and who had undergone heart transplantation during the same period. The mean age at the time of transplantation was 5.3 years and 8.2 years at the time of conversion. The causes of conversion were adverse side effects in 50% of patients, late rejection in 32% and refractory rejection in 18%. The mean time from heart transplant to conversion was 36 months and the mean follow-up period was 74 months. We observed complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (x100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (p = <0.0001). The rate of infectious episodes before conversion was 5.89 and after conversion was 4.18 (p = 0.023). There was no statistically significant difference in relation to tumor, renal failure requiring dialysis, systemic arterial hypertension, dyslipidemia, gallstones, diabetes mellitus, anemia, neurological complications, hirsutism and gingival hyperplasia after conversion. A significant incidence of cardiac allograft vasculopathy after conversion to tacrolimus was found (p = 0.004). When comparing patients on tacrolimus to patients on cyclosporine, there was a significant decrease in the incidence of rejection (p = 0.001), and infectious episodes (p = 0.002) in patients using tacrolimus. Patients converted to tacrolimus when compared to patients on cyclosporine had lower neurological complications, hirsutism and gingival hyperplasia, but higher prevalence of anemia. There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. Three deaths were secondary to rejection, and only one in the first year after transplant. Patients using tacrolimus showed greater survival rate when compared to patients taking cyclosporine. The clinical outcome of children undergoing heart transplantation and who required conversion of immunosuppressive regimen allowed us to conclude that tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option in pediatric patients
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Boachie-Ansah, G. "Adenyl compounds, adrenoreceptor activation, and acute ischaemia-related cardiac arrhythmias." Thesis, University of Strathclyde, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382268.
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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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Capewell, Simon. "Studies of the calcium antagonist felodipine in the treatment of hypertension and heart failure." Thesis, University of Newcastle Upon Tyne, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330281.
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Nicholas, Jacob. "Studies in the use of mexiletine in the coronary care unit." Thesis, Queen's University Belfast, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329369.
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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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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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Ye, Yanping. "Designing New Drugs to Treat Cardiac Arrhythmia." PDXScholar, 2012. https://pdxscholar.library.pdx.edu/open_access_etds/638.
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Heart failure resulting from different forms of cardiomyopathy is defined as the inability of the heart to pump sufficient blood to meet the body's metabolic demands. It is a major disease burden worldwide and the statistics show that 50% of the people who have the heart failure will eventually die from sudden cardiac death (SCD) associated with an arrhythmia. The central cause of disability and SCD is because of ventricular arrhythmias. Genetic mutations and acquired modifications to RyR2, the calcium release channel from sarcoplasmic reticulum, can increase the pathologic SR Ca2+ leak during diastole, which leads to defects in SR calcium handling and causes ventricular arrhythmias. The mechanism of RyR2 dysfunction includes abnormal phosphorylation, disrupted interaction with regulatory proteins and ions, or altered RyR2 domain interactions. Many pharmacological strategies have shown promising prospects to modulate the RyR2 as a therapy for treating cardiac arrhythmias. Here, we are trying to establish a novel approach to designing new drugs to treat heart failure and cardiac arrhythmias. Previously, we demonstrated that all pharmacological inhibitors of RyR channels are electron donors while all activators of RyR channels are electron acceptors. This was the first demonstration that an exchange of electrons was a common molecular mechanism involved in modifying the function of the RyR. Moreover, we found that there is a strong correlation between the strength of the electron donor/acceptor, and its potency as a channel inhibitor/activator, which could serve as a basis and direction for developing new drugs targeting the RyR. In this study, two new potent RyR inhibitors, 4-methoxy-3-methyl phenol (4-MmC) and the 1,3 dioxole derivative of K201, were synthesized which are derivatives of the known RyR modulators, 4-chloro-3-methyl phenol (4-CmC) and K201. The ability of K201, 1,3 dioxole derivative of K201 and 4-MmC to inhibit the cardiac calcium channel is examined and compared at the single channel level. All of these compounds inhibited the channel activity at low micromolar concentrations or sub-micromolar concentrations.
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D, Fleming Anne H. "The effect of nutritional knowledge on nutritional intake in individuals with heart failure." Connect to this title online, 2004. http://hdl.handle.net/1811/182.
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Senior Honors Thesis (Nursing)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains 23 p.; also includes graphics Includes bibliographical references (p. 22-23 ). Available online via Ohio State University's Knowledge Bank.
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Clark, Sarah A. "A clinical chemistry-based epidemiological study of the main causes of myocardial infarction." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390475.
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Maharsy, Wael. "Enhancing Cardiomyocyte Survival in Drug Induced Cardiac Injury." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23384.
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Cardiotoxicity associated with many cancer drugs is a critical issue facing physicians these days and a huge hurdle that must be overcome for a side effects-free cancer therapy. Survival of cardiac myocytes is compromised upon the exposure to certain chemotherapeutic drugs. Unfortunately, the mechanisms implicated in cardiac toxicity and the pathways governing myocyte survival are poorly understood. The following thesis addresses the mechanisms underlying the cardiotoxicity of two anticancer drugs, doxorubicin (DOX) and Imatinib mesylate (Gleevec). Transcription factor GATA-4, has recently emerged as an indispensable factor in the adult heart adaptive response and cardiomyocyte survival. Therefore, the specific aim of this project was to determine the role of GATA-4, its upstream regulators, as well as partners in survival. A combination of cell and molecular techniques done on in vivo, and ex vivo models were utilized to tackle these issues. In this study, we confirmed the cardiotoxicity of the anticancer drug, Imatinib mesylate and found to be age dependent. GATA-4, already known to be implicated in DOX-induced toxicity, was confirmed as an Imatinib target. At the molecular level, we identified IGF-1 and AKT as upstream regulators of GATA-4. Moreover, we confirmed ZFP260 (PEX-1), a key regulator of the cardiac hypertrophic response, as a GATA-4 collaborator in common prosurvival pathways. Collectively, these results provide new insights on the mechanisms underlying drug-induced cardiotoxicity and raise the exciting possibility that cancer drugs are negatively affecting the same prosurvival pathway(s), in which GATA-4 is a critical component. Therapeutic interventions aimed at enhancing GATA-4 activity may be interesting to consider in the context of treatments with anticancer drugs.
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Economos, Demetri. "Regulation of intracellular free calcium in heart and vascular smooth muscle by drugs and hormones." Thèse, Université de Sherbrooke, 1992. http://hdl.handle.net/11143/12085.
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Résumé: La contraction du muscle excitable, comme le muscle cardiaque et le muscle lisse vasculaire, dépend surtout de l'entrée du Ca2+ à l'intérieur de la cellule (ou la libération du [Ca]i) via des canaux voltages dépendants (de type T ou L) ou des canaux opérés par récepteurs. Le but de cette étude est de vérifier si certaines hormones comme l'insuline, l'endotheline-1 et la bradykinine augmentent le [Ca]i des cellules cardiaques et vasculaires via la stimulation des canaux calciques par un mécanisme qui est indépendant de l'activation des récepteurs. De plus, on a étudié les effets d'un agent pharmacologique, le BRL 34915, un ouvreur des canaux KATP afin de vérifier l'hypothèse que certains canaux Ca2+ dépendants du voltage peuvent être modulés indirectement par une hyperpolarisation de la membrane cellulaire. En utilisant la méthode de mesure du [Ca]i à l'aide de fura-2, nous observons au repos que le [Ca]i dans les cellules cardiaques de l'embryon de poulet, ainsi que dans les cellules du foetus humain âgé de 10 à 20 semaines et également les cellules aortiques du lapin, est près de 100 nM. La dépolarisation de la membrane de ces cellules avec du 30 mM du [K]o induit une augmentation rapide transitoire du [Ca]i, qui est suivie par une composante soutenue. L'augmentation transitoire de [Ca]i par 30 mM de [K]o est bloquée par des antagonistes des canaux calciques de type L tel la nifédipine. La composante calcique soutenue est insensible à plusieurs bloqueurs calciques comme la nifédipine et la vérapamil. Par contre, cette composante soutenue est bloquée par l'EGTA et le bloqueur calcique le PN200-110. L'ouvreur des canaux KATP, le BRL, diminue le [Ca]i induit par une haute [K]o. L'insuline et l'ET-1 induit surtout une augmentation soutenue du [Ca]i. Par contre la bradykinine induit une composante rapide transitoire suivie par une augmentation soutenue. L'effet de l'ET-1 sur la composante soutenue est insensible à l'antagoniste réceptoriel de type ET-A le BQ123. L'antagoniste du récepteur B1 de la bradykinine ainsi que la caféine diminuent la composante calcique transitoire sans affecter la composante soutenue induite par la bradykinine. En utilisant la méthode du "patch clamp" en configuration d'une cellule entière, le BRL 34915 augmente un courant sortant retardé et hyperpolarise la membrane. Par contre, l'insuline et l'ET-1 n'affectent pas le courant K+ sortant retardé et les courants calciques de type T et L. La bradykinine n'affecte pas non plus le courant K+ mais elle augmente les courants Ca2+ de type T et L. Ces résultats suggèrent que l'augmentation du [Ca]i par un agoniste dans les cellules cardiaque et vasculaire peut être médiée via la stimulation d'un récepteur, ou via un mécanisme qui est indépendant du récepteur.||Abstract: The contraction of excitable cells such as cardiac and vascular smooth muscle cells depend mainly on the entry of Ca2+ via voltage dependent Ca2+ channels (VOC) or receptor operated Ca2+ channels (ROC). The aim of this work is to verify if some hormones such as insulin, ET-1 and bradykinin increase [Ca]i in single cells of chick embryos, human fetuses, and rabbit aortic single cells via mechanisms that are receptor independent. Also, we studied the effect of a KATP channel opener (BRL 34915) in order to verify the hypothesis that [Ca]i could be modulated indirectly by this substance via increasing a delayed outward K+ current and hyperpolarization of the cell membrane. Using the fura-2 Ca2+ measurement technique, the intracellular free Ca2+ of our three different preparations was near 100 nM. Depolarization of the membrane of both heart and VSM cells with continuons superfusion of 30 mM [K]o induced a rapid transient increase of [Ca]i that was followed by a sustained component. The early transient increase of [Ca]i by high [K]o was blocked by the L-type Ca2+ channel antagonist nifedipine. However, the sustained component was found to be insensitive to this drug. PN200-110 another L-type Ca2+ blocker was found to decrease both the early and sustained increase of [Ca]i induced by sustained depolarization. Insulin and ET-1 produced a dose dependent sustained increase of [Ca]i that was blocked by PN200-110 or by lowering the [Ca]o with EGTA. However, bradykinin induced both a transient and sustained increase of [Ca]i. The transient increase of [Ca]i by bradykinin was decreased in presence of caffeine and the bradykinin B1 receptor antagonist. However, the sustained increase of [Ca]i induced by ET-1 or bradykinin was insensitive to ET-1 or bradykinin receptors antagonists. Using the whole-cell voltage clamp technique, only BRL 34915 was found to increase a delayed outward K+ current and hyperpolarize the cell membrane. Bradykinin, but not insulin or ET-1, increased both T and L- type ICa. These results suggest that the early increase of [Ca]i by a hormone could be mainly due to stimulation of L (and T-) type Ca2+ channels and seem to be mediated via receptor dependent mecanism. However, the sustained increase of [Ca]i by a hormone could be due to stimulation of a Ca2+ channel via mechanism that is receptor independent. Also, voltage dependent Ca2+ channels could be indirectly mediated by channels that modulate the resting membrane potential.
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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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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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Hopmeyer, Joanne. "Effect of physiologic parameters on the quantification of mitral regurgitation using the flow convergence method." Diss., Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/10969.
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Jaffray, Mariesha A. "The MEDMAN study : implementing change at the community pharmacy/general practice interface." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158336.
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Introduction Management of coronary heart disease (CHD), a major cause of mortality and morbidity in the UK, in primary care, remains sub-optimal. This work aimed to: evaluate impact of a community pharmacy-led intervention on appropriateness of treatment and quality of life of CHD patients; describe opinions and experiences of community pharmacists and GPs and use management of change literature as an explanatory framework for the findings. Methods The thesis comprises: two literature reviews (pharmacy-led interventions for CHD and NHS-based studies using change theories); an RCT evaluating the service; questionnaire surveys and qualitative interviews with community pharmacists and GPs, and comparison of a new model of change with two change theories. Results Review of pharmacy interventions revealed only small-scale studies demonstrating benefit for CHD patients. The change review revealed use of change management theories to implement change and as explanatory frameworks for change initiatives, in the NHS, but not in the pharmacy setting. The RCT recruited 1493 patients (980 intervention, 513 control), 70 pharmacies (102 pharmacists) and 48 practices (208 GPs). No significant differences were found in primary outcomes (appropriateness of treatment or quality of life). Questionnaires revealed positive attitudes to the service but need for pharmacist access to patient records and improved GP/community pharmacist relationships. Qualitative interviews indicated more divergent views. Attitudes were influenced by understanding and previous experience of medicines management, change drivers and implementation processes. Themes conceptualised into a ‘change readiness’ model, had similarities with Lewin’s planned change approach and Pettigrew’s receptivity model. All three models identified areas of sub-optimal intervention implementation and delivery. The new service did not improve appropriateness of treatment or quality of life because it was implemented and delivered sub-optimally. There is a need for greater use of an evidence based systematic approach to introduce new services, but research is required to confirm this approach would confer the hypothesised benefits.
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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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Hutton, Therese. "The effect of serum on the hypodynamic frog heart." Thesis, University of Central Lancashire, 1989. http://clok.uclan.ac.uk/21032/.
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An investigation was made of the effects of serum and serum fractions on the isolated spontaneously beating frog heart preparation. Initial experiments were performed to develop a sensitive bioassay preparation to test for inotropic agents in serum. The isolated spontaneously beating frog heart was found to be sensitive, reliable and responded consistently to serum and its components. During the development of the bioassay it was found that the heart became weak after prolonged perfusion. An investigation was then made to determine the mechanism underlying the development of the hypodynamic (weak) condition of the isolated heart. It was found that a heart which was immersed in static oxygenated Ringer's solution did not become hypodynamic. Continuous perfusion (washing) of the external surface of the heart led to partial development of the hypodynamic state. However when external perfusion was combined with internal perfusion, the onset of the hypodynamic state was faster reaching a steady-state of around 50% of the original tension after 150 minutes. During this steady state the preparation was used to investigate the inotropic effects of serum, serum fractions and several metabolic substrates including pyruvate, lactate and creatine on the heart. A comparative study was made in order to determine the oxygen consumption and the levels of endogenous lactate, pyruvate and creatine phosphate in the fresh and hypodynamic hearts. The levels of lactate, pyruvate and creatine phosphate were significantly decreased in the hypodynamic hearts comparea with normal preparations. Oxygen consumption was unchanged and contractile force decreased by 47% in the hypodynamic hearts. These initial results show that the development of the weak condition of the heart may be associated with a metabolic deficiency of the myocardium. Perfusion of the isolated spontaneously beating hypodynamic frog heart with dialysed serum taken from several animal species evoked both positive inotropic and chronotropic responses in the presence of cy•adrenergic (phentolamine),/3-adrenergic (propranolol) and cholinergic antagonists (atropine). These effects were dose-dependent. The cardioactive component(s) of serum were separated using several fractionation techniques. These included gel filtration on C50 and C200 Sephadex, filtration on Amicon microconcentrators and ultrafiltration on PM30 and XM100A membranes. During the separation procedures the fractions were tested for inotropic activity compared with dialysed serum. A fraction corresponding to serum albumin in molecular weight (60000-63000) evoked a positive inotropic effect on the heart. Commercial serum albumin evoked no net effect on the heart. Serum and its fractions were subjected to physical and chemical treatments including boiling, pH changes, chymotrypsin and lipase treatment and lipid extraction in an attempt to determine the nature of the cardioactive component(s). During the various stages of treatment the fractions were tested on the heart for bioactivity. Boiling, pH changes and chymotrypsin treatment failed to denature the cardioactive component of serum corresponding to serum albumin in molecular weight. After these treatments a positive inotropic response was still retained. Similar responses were obtained with a lipid extract of serum. However, the activity of these fractions disappeared after treatment with the enzyme lipase suggesting that that the cardioactive component has lipid like properties. No attempt was made to identify and characterise this unknown lipid due to lack of time. In conclusion, the present study demonstrates that serum contains a lipid—like cardioactive fraction which may be associated with serum albumin. It evokes positive inotropic and chronotropic effects on the isolated hypodynamic frog heart.
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Pace, Diane Todd. "Effect of postmenopausal hormone replacement on heart rate variability." View the abstract Download the full-text PDF version, 1998. http://etd.utmem.edu/ABSTRACTS/1998-003-pace-index.html.
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Thesis (Ph.D)--University of Tennessee Health Science Center, 1998.Title from title page screen (viewed on October 17 2008). Research advisor: Kay F. Engelhardt. Document formatted into pages (xi, 162 p. : ill.). Vita. Abstract. Includes bibliographical references (p.162).
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Hart, Matthew Thomas. "The Effects of Aerosol Drug Delivery on Airway Resistance through Heat-Moisutre Exchangers." Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/rt_theses/4.
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Introduction: The use of heat moisture exchangers (HMEs) is becoming more popular with many institutions delivering aerosolized medications between the HME and the endotracheal tube of patients being mechanically ventilated. When HMEs become saturated resistance can increase which can cause changes that can lead to patient-ventilator dysnchrony, development of intrinsic PEEP, and weaning difficulty. The purpose of this study was to determine the effects of aerosol drug delivery on resistance through heat-moisture exchangers. Method: An in-vitro model to simulate exhaled heat and humidity from a patient’s lungs was developed by connecting the test lung to a cascade humidifier that was placed between the endotracheal tube and the test lung. Temperature (37 ºC) and relative humidity (100%) were held constant through all test runs. Ventilator settings used for the study were as follows: Tidal volume 500 mL, frequency 15/min, PEF 60 L/min, PEEP 5 cmH2O, bias flow 2 L/min and I:E ratio 1:3.The pressurized metered-dose inhaler (pMDI; ProAir HFA) with a minispacer (Thayer Medical), hand-held nebulizer (HHN; Salter Labs) and placebo (No aerosol generator or medication) were compared. Albuterol sulfate (2.5 mg/3 ml) was administered through continuous HHN and six puffs of albuterol were given from a pMDI equaling one treatment. Neither medication nor aerosol device was used with the placebo group in order to determine the effect of HME on airway resistance during mechanical ventilation. Six aerosolized treatments were given to simulate a patient receiving albuterol every four hours over a twenty-four hour period. While five minutes was allowed between treatments, airway resistance was measured via the ventilator before and after the administration of the placebo, pMDI and HHN, which equaled five-minute intervals. Data Analysis: Descriptive statistics, dependent t-tests, one-way analysis of variance (ANOVA), repeated measures ANOVA and post-hoc multiple comparisons were utilized for the data analysis of this study, using SPSS version 16.0. A p-value<0.05 was considered significant. Results: There is a linear time effect with means of airway resistance increasing overtime not only with the placebo but also with the pMDI and nebulizer. At the end of all treatments, the means of resistance with the placebo, pMDI and nebulizer were 9.31 cmH2O/L/sec, 9.37 cmH2O/L/sec and 11.20 cmH2O/L/sec, respectively. While no significant difference was found between the placebo and the pMDI (p=0.452), the nebulizer significantly increased airway resistance when compared to placebo (p=0.004) and the pMDI (p=0.02). Conclusion: Airway resistance increases with use of the placebo, pMDI, and JN groups. Aerosol generators showed a greater increase in resistance when compared to placebo with the greater increase in resistance by HHN.
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McCabe, Christopher. "The effects of drugs acting at endothelin receptors on the cardiac electrophysiology of normal and ischaemic rabbit hearts." Thesis, University of Strathclyde, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401508.
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Mauck, Rebecca A. "The effect of prior education on the learning effect associated with the six-minute walk test in patients with congestive heart failure." Virtual Press, 2003. http://liblink.bsu.edu/uhtbin/catkey/1260490.
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A learning effect has been shown to be present in the repeated performance of the six-minute walk test and contributes to the variability of walk distance up to the third walk test. The purpose of this study was to see if education about the performance of the walk test could minimize the learning effect. It was hypothesized that education about the learning effect would decrease the learning effect. There were a total of 18 subjects (5 female and 13 male) with a mean age of 63.7+12.1 years that completed three standardized six-minute walk tests. The subjects were randomly assigned to either a Learning Effect Education (LEE) group or a Usual Care (UC) group. The LEE group was provided with education material about the learning effect approximately two days prior to their first walk test, with additional instruction immediately prior to their first walk test. The mean walk distances for the LEE group over the three walk tests were 1,248±297.4, 1,361.9±275.7, and 1,355.1+291.7 feet, respectively. Mean walk distances for the UC group over the three walk tests were 1,149.6+392.3, 1,123.6+427.5, and 1,209.9±368.7 feet, respectively. The hypothesis was tested and the repeated measures ANOVA showed a significant (p=0.033) interaction between the groups with respect to six-minute walk distance. A Bonferroni's post hoc analysis showed that mean walk distance (113.9+42.3 feet) increased significantly (p=0.048) from test one to test two in the LEE group. There was no significant difference between mean walk distance from test two and test three (6.8+31.1 feet) in the LEE group. In the UC group, there was no significant increase in mean walk distance from test one to test two (-26+42.3 feet), while there was a significant (p=0.04) increase in mean walk distance from test two to test three (86.3+31.1 feet). There was a significant difference between walk tests (p=0.011) with no significant difference between groups (p=0.333). In conclusion, the results from this study suggest that education may reduce the number of familiarization trials needed prior obtaining an accurate baseline six-minute walk test distance.School of Physical Education
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Ridgway, Andrea Janina. "Ultrasound doppler evaluation of mechanical aortic heart valves." Thesis, Georgia Institute of Technology, 1986. http://hdl.handle.net/1853/10213.
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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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