Resumo: A mamoneira (Ricinus communis L.) é uma espécie oleaginosa tropical, sendo o óleo extraído de suas sementes um dos mais versáteis da natureza e com inúmeras aplicações industriais. Embora ainda seja uma espécie rústica, ela está sujeita a diversas doenças, dentre elas o mofo-cinzento, causada pelo fungo Amphobotrys ricini. O melhoramento genético seria a melhor alternativa para o controle da doença, mas demanda tempo para se obter cultivares resistentes. Dessa Maneira, o uso de métodos de controle baseado em métodos químicos, alternativos ou biológicos mostra-se viável em curto prazo. O objetivo do trabalho foi estudar a eficiência de controle do mofocinzento, na cultura da mamoneira, utilizando-se de métodos químico, alternativo e biológico. Para tanto, foram verificados, in vitro, a eficiência de diferentes meios de cultura na esporulação do patógeno e do antagonista C. rosea. Verificou-se, também, a produção de escleródios do patógeno nos meios. Quanto à eficiência dos métodos, verificou-se, in vitro, a eficiência deles na inibição do crescimento micelial e da germinação dos conídios do patógeno. Após desenvolver e validar uma escala diagramática de avaliação de severidade da doença em racemos de mamoneira, verificou-se a eficiência de aplicação do antagonista C. rosea em frutos destacados da mamona inoculados com o patógeno. Em plantas submetidas a condições de estufa e em campo, verificou-se a eficiência dos métodos no controle da doença causada por A. ricini Quanto à esporulação, o melhor meio de cultura para o patógeno foi V8-20%, obtendo 5,7 x 106 conídios/mL. Para o antagonista C. rosea, o melhor meio foi o TJ- 5% (Suco de Tomate), produzindo 4,41 x 106 conídios/mL. O único meio que propiciou abundante produção de escleródios de A. ricini foi o aveia-ágar. Quanto a inibição do crescimento micelial do patógeno... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The castor bean (Ricinus communis L.) is a tropical oily species, and the oil extracted of its seeds is one of most versatile of the nature, with many industrial applications. Even being a rustic species, it still subjects to several diseases, between them the gray mold, caused by the fungus Amphobotrys ricini. The genetic breeding would be the best alternative for the disease control, but spend time to get a resistant cultivar. In this way, the use of methods of control based on chemical, alternative or biological methods shows viable in short time. The aim of this work was to study the efficiency of the control of gray mold, on castor bean crop, using chemical, alternative and biological methods. Therefore, they had been verified, in vitro, the efficiency of different culture medium in the pathogen sporulation and the antagonist C. rosea. The sclerotia production in the culture medium can be also verified. About the efficiency of the methods, in vitro, the inhibition of the mycelial growth and germination of conidia was verified. After to develop and to validate a diagrammatic scale of evaluation of severity of the disease in racemes of castor bean, the efficiency of application of the antagonist C. rosea in inoculated fruits detached of castor bean with the pathogen was verified. In plants submitted to greenhouse and field conditions, the efficiency of the methods in the control of the disease caused by A. ricini was verified About the sporulation, the optimum culture medium for the pathogen was V8-20%, getting 5,7 x 106 conidia/mL. For the antagonist... (Complete abstract click electronic access below) / Orientador: Maurício Dutra Zanotto / Coorientador: Edson Luiz Furtado / Banca: Francisco Luiz Araújo Câmara / Banca: Cezar Junior Bueno / Mestre

O uso de fármacos cardiovasculares tem aumentado consideravelmente nos últimos anos, incluindo o uso de beta-bloqueadores como o metoprolol. E embora estudos experimentais e clínicos tenham demonstrado benefícios na utilização desta classe de fármacos em pacientes sépticos, o bloqueio de receptores beta-adrenérgicos continua sendo contraditório, especialmente no choque séptico. Vinte fêmeas suínas nas quais o choque séptico foi induzido através da infusão intravenosa de Escherichia coli (6x109 UFC/kg em duas horas), foram randomicamente distribuídas (n=10 por grupo) em um grupo Metoprolol (GM; 214.2 ?g/kg de metoprol infundido em 45 minutos) ou grupo Controle (GC), o qual recebeu um volume correspondente de solução salina. Os parâmetros hemodinâmicos e de oxigenação foram avaliados no momento basal (TB), T30, T60, T120, T240 e T360 minutos. Amostras de sangue foram colhidas ainda em TB, T120 e T360 e armazenadas para posterior mensuração da concentração sérica de citocinas e marcadores cardíacos. Durante este período utilizou-se um protocolo de ressuscitação com Ringer lactato, norepinefrina (NE) e dobutamina para manutenção da pressão arterial média (PAM) > 65 mmHg, da pressão venosa central (PVC) em 8-12 mmHg e da saturação venosa mista de oxigênio (SvO2) > 65%. Os dados paramétricos foram analisados utilizando ANOVA de duas vias para medidas repetidas, seguidas por Tukey quando necessário, enquanto para os dados não paramétricos utilizaram-se os testes de Kruskall-Wallis e Mann-Whitney. A quantidade de fluido, NE e dobutamina foi analisada pelo teste t de Student, e a análise de sobrevivência foi realizada utilizando o Kaplan-Meier log-rank test. Exceto por um valor mais elevado do índice de resistência vascular sistêmica (IRVS) em T240 (p=0,02) nos animais tratados com metoprolol, todos os parâmetros analisados neste estudo apresentaram um comportamento similar em ambos os grupos. Nenhuma diferença foi observada também em relação ao volume total de fluido (p=0,914), à quantidade total de NE (p=0,069) e dobutamina (p=0,560) administrada, e ainda em relação à mortalidade. Embora estudos tenham demonstrado diversos benefícios na utilização de beta-bloqueadores em pacientes sépticos, e que estes tenham demonstrado resultados promissores, a administração de metoprolol não apresentou benefícios em nenhum dos parâmetros analisados em nosso modelo experimental. Porém, em um cenário onde a administração de beta-bloqueadores está em constante crescimento, é de grande importância saber que sua administração não apresenta efeitos deletérios nestes pacientes / The use of cardiovascular drugs considerably increased in recent years, including the use of ?-blockers, such as metoprolol. And although experimental and clinical studies had demonstrated benefits on the administration of these drugs in septic patients, the ?-blockade is still contradictory, especially in the septic shock. Twenty female pigs in which septic shock was induced through intravenous E. coli infusion (6x109 c.f.u/kg in 2h) were randomly assigned (n=10 per group) to the Metoprolol group (214.2 ?g kg-1 of metoprol infused in 45 minutes) or Control group, which received a correspondent volume of normal saline. Hemodynamic and oxygenation parameters were then evaluated at baseline (TB), T30, T60, T120, T240 and T360 minutes. Blood samples were collected at TB, T120 and T360 for posterior mensuration of serum cytokines and cardiac markers. During this period, a resuscitation protocol with lactated Ringer\'s solution, norepinephrine and dobutamine was used to maintain the mean arterial pressure (MAP) > 65 mmHg, the central venous pressure (CVP) between 8-12 mmHg and the mixed venous oxygen saturation (SvO2) > 65%. Parametric data were compared using the two-way repeated measures ANOVA, followed by the Tukey test when necessary, while the nonparametric data were analyzed with the Kruskall-Wallis and the Mann-Whitney test. The total volume of fluid and total amount of norepinephrine and dobutamine infused were analyzed by the Student\'s t-test. Survival analysis was performed using Kaplan-Meier log-rank test. Except for the higher values of systemic vascular resistance index (SVRI) at T240 (p=0.02) in the animals that received metoprolol, all the parameters analyzed in this study showed a similar behavior in both groups. No difference was also observed between groups in relation to the total volume of fluid (p=0.914), the total amount of norepinephrine (p=0.069) and dobutamine (p=0.560) infused, and related to the survival rate. Although some studies have demonstrated several benefits with the use of beta-blockers in patients with sepsis and show promising results, the administration of metoprolol did not improve any of the parameters analyzed in our experimental model. However, in a scenario where the administration of ?-blockers is increasing constantly, it is important to know that its administration do not present deleterious effects in these patients

Magister Pharmaceuticae - MPharm / The declining efficacy of antimalarial drugs against resistant Plasmodium falciparum strains in several endemic regions has amplified the world’s burden of neglected diseases. This has highlighted the need for alternate strategies for chemotherapy and chemoprophylaxis. Since malaria is prevalent primarily in third world countries, it is critical for novel therapies to be affordable. Previous research has found that some antihistamines possess inherent antimalarial activity and cause a marked reversal of chloroquine resistance in vitro and in vivo. Promising results have been demonstrated when chlorpheniramine was combined with chloroquine to reverse chloroquine resistance in two African studies (Sowunmi et al, 1997; Abok., 1997).Recently, astemizole and its principle human metabolite desmethylastemizole were identified as potent inhibitors of Plasmodium falciparum at sub-micromolar concentrations in both chloroquine sensitive and chloroquine resistant parasites, showing efficacy in vitro and in two mouse models. The promising results observed with these studies warrant a more comprehensive understanding of how antihistamines interact with the malaria parasite. Additionally, analysing the different structural and mechanistic characteristics of antihistamines may lead to the design and development of effective and affordable antimalarial agents or chloroquine resistance modulators.This thesis describes the antimalarial activity of mainly off-patent (generic) antihistamines by comparing the efficacy of a total of 24 antihistamines, representing histamine1, histamine2, and histamine3 receptor antagonists, against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Cyproheptadine, ketotifen, loratadine, desloratadine, 3-(1HImidazol-4-yl) propyldi (p-fluorophenyl) methyl ether hydrochloride and ciproxifan display IC50 values less than 4μg/ml. There was no significant difference in the sensitivity to antihistamines among the chloroquine sensitive and resistant parasites tested. A tricyclic nucleus appears to be an important structural scaffold for antihistamines which exhibit low IC50 values. Synergistic studies indicate that enhancement of the antimalarial effect of chloroquine on P.falciparum was observed with the ethanolamines against the chloroquine sensitive parasites.Cyproheptadine, ketotifen and desloratadine exerted a marked synergistic action with chloroquine against chloroquine sensitive and resistant parasites. Chlorpheniramine exhibited synergism with chloroquine against resistant parasites only.Microscopic studies illustrate the effect of antihistamines on parasite morphology when compared to control. Using immunofluorescence microscopy, it was seen that ketotifen decreases haemoglobin localization while cyproheptadine increases haemoglobin localization in the parasite’s food vacuole. Western blots have confirmed these results, in addition to indicating that chlorpheniramine decreases the haemoglobin content in the parasite. The results confirm that certain antihistamines do indeed cause a reduction in the growth of malaria parasites. Furthermore, the histamine1 and histamine3 receptor antagonists are most active while histamine2 receptor antagonists have no antimalarial activity. Microscopic studies suggest that antihistamines do not exert their antimalarial effect via a single mechanism of action.I wish to express my sincere appreciation to the following people and institutions whose supervision and assistance made the presentation of this thesis possible:My supervisor, Prof. Henry Leng. Thank for always believing in me. Your encouragement, kindness and calm temperament has given me the strength to complete this thesis even when times were tough. Your wisdom and understanding will always be remembered.My co-supervisor, Prof. Pete Smith. I sincerely thank you for allowing me the opportunity to work in your laboratory and for welcoming me into the department. Your kindness and welcoming attitude will forever be appreciated. Thank you for always being patient and understanding.Dr. Uschi Wiehart. Thank you for all the help in the laboratory and always being there for me. I truly value and appreciate your contribution to this thesis. Your friendship has added so much positive energy to my life. Thank you for your wisdom, inspirational advice and unfaltering encouragement Sumaya and Ntokosi, your help, advice and company in tissue culture, are truly appreciated.The UCT, Pharmacology students. Thank for all your assistance.My dearest Pharmaceutical Chemistry colleagues, Jaques Joubert, for your friendship and support and for always listening and Prof. Peter Eagles, your kindness, support and wise advice has given me strength when I needed it most. To my other School of Pharmacy colleagues. Prof. Sarel Malan and team, for your support and motivation.To my family for all your support and wisdom and to my baby brothers; Omar and Uzair for all the joy that you bring to my life.And finally to my dearest husband, Zaheer for all your love and support throughout my studies and for taking me to UCT to culture parasites every weekend

The purpose of this research is to help people who have been hurt by bad leadership, and also to find out why they move from one church to the other. This is an undercover issue since in most cases the Pentecostal church family projects strength than weakness. This study deals with people who have been hurt by bad leadership that verbally attacks and curses them from the pulpit. The pulpit is already a position of power and if not handled rightly, it has negative ramification on the hearers. One of it is the mobility of membership, from one Assembly to the other in search for more understanding and encouraging atmosphere.This particular abuse of power has been a burning issue within some of the Pentecostal churches and has been overlooked and without any redress. Therefore this thesis attempts through pastoral care approach, to deal with these issues, that have affected some church members. The problem in the study has been extensively explained and a method of helping and healing those that are hurt is also projected substantially. The different types of leadership and leadership qualities are also tabulated and explained to enable an understanding that people deserve a better approach. Since the researcher has been in the church for a long time, and through observation has experienced how some people were verbally abused from the pulpit has motivated her to conduct a research. Specially, on how to care for those who are wounded in spirit, as she mentioned some of the members have been hurt for almost three decades, yet they are still looking for a church where they can be spiritually fulfilled. It is appropriate to make this valuable research in the field of practical theology as the generated knowledge, shall help the people to heal the hurts and stabilize. It is reasonable to surmise that when a miss-normal is perpetuated without any challenge it takes a toll and becomes a standard behaviour. This research refuses to remain silent and has exposed and projected a healing solution to the plight of members that the pulpit victimises whether consciously and unconsciously. The willingness of the interviewees in these case studies is also highly commended as it roots the studies in concrete realities and generates lessons that are based on real life research. Copyright / Dissertation (MA(Theol))--University of Pretoria, 2013. / Practical Theology / unrestricted

Class III antiarrhythmic drugs share the common mechanism of widening the cardiac action potential without affecting conduction velocity. This thesis reports on the actions of newly developed putative Class III antiarrhythmic drugs, tedisamil, KC 8851, RP 62719, UK 68798, and risotilide, as well as an ATP-sensitive K⁺ channel blocker, glibenclamide. Studies were performed to examine the actions of these drugs in acute myocardial ischaemia and possible mechanisms responsible for these actions. The hypothesis tested was that drug treatment prevented arrhythmias induced by acute myocardial ischaemia. Species dependent actions of these drugs on ECG and blood pressure were examined in rats, guinea pigs, pigs and primates. The five putative class III drugs listed above were assessed for antiarrhythmic activity in a conscious rat model of myocardial ischaemia. It was found that only tedisamil and KC 8851, which widened the Q-T[formula omitted] interval of the ECG (by up to 65%) , were effective at suppressing fibrillation in this species. None of the drug treatments decreased the incidence of ventricular premature beats. Tedisamil, but not glibenclamide, prevented tachycardias in a rat model of myocardial ischaemia- and reperfusion-induced arrhythmias. In an anaesthetized pig model of acute myocardial ischaemia, tedisamil and UK 68,798 were shown to mildly prolong the Q-T[formula omitted] interval by less than 20%, but protection against arrhythmias was equivocal. In further studies, tedisamil and UK 68,798 were compared to each other for effects on ventricular epicardial action potential morphology using intracellular recording in vivo, and effects on ventricular effective refractory period using electrical stimulation in vivo in both rats and guinea pigs. Tedisamil (4 mg/kg, i.v.) prolonged rat ventricular epicardial action potential duration fourfold in vivo, while UK68,798 (up to 1 mg/kg, i.v.) was ineffective in this species. Tedisamil (4 mg/kg, i.v.) widened guinea pig ventricular epicardial potentials by 80%, while UK 68,798 (25 μg/kg, i.v.) increased these by 30%. Action potential widening paralleled increases in ventricular refractoriness to electrical induction of premature beats. It was found that the species selective actions of these drugs was most likely related to differences in selectivity for K⁺ channels which contribute to repolarization in myocardium. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

The purpose of my study was to determine and compare the effects of three calcium antagonists on systemic hemodynamics, ECG, blood flow distribution, tissue conductance and venous tone of the rat. The effects of a representative drug from Spedding's (1985) three subclasses of calcium antagonists on systemic hemodynamics, ECG, cardiac output and the distribution of blood flow were investigated by the microsphere technique in pentobarbital-anesthetized rats. The representative drugs were: I, nifedipine (12 and 35 µg/kg/min); II, verapamil (43 and 83 µg/kg/min) and III, flunarizine (174 and 275 µg/kg/min). Low and high doses were selected to give a decrease in mean arterial pressure of 10 and 20 mmHg, respectively, compared with control rats. At equal depressor levels, all the drugs similarly decreased total peripheral resistance while slightly but not significantly increasing cardiac output (CO) and stroke volume. Heart rate was decreased by verapamil and flunarizine, but increased by nifedipine. The high dose of nifedipine decreased contractility as measured by dP/dt and had no effect on PR-interval, while verapamil decreased dP/dt and prolonged the PR-interval. The low dose of nifedipine and both doses of flunarizine slightly but not significantly decreased dP/dt and had no effect on PR-interval. All three drugs similarly affected the distribution of blood flow. Blood flow to lungs, liver, and heart was increased while flow to the intestine, kidneys, spleen and skin was decreased. Arterial conductances in lungs, liver, heart and skeletal muscle were increased by the three drugs. These results show that representative drugs from the three subclasses of calcium antagonists had similar effects on the distribution of blood flow and arterial conductances but different chronotropic, dromotropic and inotropic effects. A final set of experiments were designed to evaluate calcium antagonist actions on venous tone, as venous tone is a primary determinant of CO and the calcium antagonists generally increase CO. The effects of three calcium antagonists, verapamil, nifedipine and flunarizine on mean arterial pressure (MAP), heart rate (HR) and mean circulatory filling pressure (MCFP), an index of total body venous tone, were investigated in the. conscious rat. Infusions of all three drugs caused a dose-dependent decrease in MAP and an increase in MCFP, compared with the corresponding values in control rats. HR was decreased by verapamil and flunarizine and slightly increased by nifedipine. Further experiments investigated whether the increase in MCFP by verapamil was indirectly caused by reflex activation of the autonomic nervous system. Rats were pretreated with a continuous infusion of the ganglionic blocker hexamethonium prior to infusion of verapamil. After treatment with hexamethonium, verapamil did not increase the MCFP. In fact the highest dose of verapamil significantly decreased MCFP. The results suggest that calcium antagonists have greater dilator effects in arterioles compared to veins. It appears that any direct venodilator effects of verapamil in conscious rats are masked due to reflex activation of the autonomic nervous system. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Changes in spontaneous spike activities recorded from murine frontal cortex networks grown on substrate-integrated microelectrodes were used to determine the dissociation constant (KB) of three GABAA antagonists. Neuronal networks were treated with fixed concentrations of GABAA antagonists and titrated with muscimol, a GABAA receptor agonist. Muscimol decreased spike activity in a concentration dependent manner with full efficacy (100% spike inhibition) and a 50% inhibitory concentration (IC50) of 0.14 ± 0.05 µM (mean ± SD, n=6). At 10, 20, 40 and 80 µM bicuculline, the muscimol IC50 values were shifted to 4.3 ± 1.8 µM (n=6), 6.8 ± 1.7 µM (n=6), 19.3 ± 3.54 µM (n=10) and 43.5 µM (n=2), respectively (mean ± SD). Muscimol titration in the presence of 10, 20, 40 µM of gabazine resulted in IC50s values of 20.1 (n=2), 37.17 (n=4), and 120.45 (n=2), respectively. In the presence of 20, 80, and 160 µM of TMPP (trimethylolpropane phosphate) the IC50s were 0.86 (n=2), 3.07 (n=3), 6.67 (n=2) µM, respectively. Increasing concentrations of GABAA antagonists shifted agonist log concentration-response curves to the right with identical efficacies, indicating direct competition for the GABAA receptor. A Schild plot analysis with linear regression resulted in slopes of 1.18 ± 0.18, 1.29 ± 0.23 and 1.05 ± 0.03 for bicuculline, gabazine and TMPP, respectively. The potency of antagonists was determined in terms of pA2 values. The pA2 values were 6.63 (gabazine), 6.21 (bicuculline), and 5.4 (TMPP). This suggests that gabazine has a higher binding affinity to the GABAA receptor than bicuculline and TMPP. Hence, using spike rate data obtained from population responses of spontaneously active neuronal networks, it is possible to determine key pharmacological properties of drug-receptor interactions.

No description available.

The naturally occuring ergot alkaloids of the fungus, Claviceps purpurea, and their many derivatives have been of neuropharmacological interest for many years because of their ability to affect peripheral and central adrenergic and serotonergic systems. More recently, selected compounds such as lergotile (2-chloro-6-methyl ergoline-8-beta acetonitrile) and and bromocriptine (2-bromo-alpha-ergocryptine), have been given additional attention due to their possible therapeutic potential in the treatment of parkinson’s disease, acromegaly and other disorders. There have been considerable data published attempting to establish the mechanism(s) whereby the ergot compounds exert their effects. A large portion of these experiments involves the interaction of ergot compounds with dopaminergic systems. This is a logical course of study, since many of the actions of the ergot compounds mimic the actions of compounds known to affect dopaminergic neurons, e.g. antagonists such as the phenothiazines and butyrophenones and agonists such as levodopa and apomorphine. In the last decade, much attention also has been focused on the role of serotonin (5-hydroxytryptamine) in the mediation of dopaminergic systems. There have been many conflicting reports published as to the role of serotonin but it is still uncertain whether or not serotonin does indeed play a role. The present study investigates two dopaminergic effects of the standard dopamine agonist apomorphine and the ergoline lergotrile and the similarities or differences that exist when serotonergic function is altered.

Using the method of qualitative content analysis, my research is focused on the visual and ideological representation of antagonists in eight PC games of first-person shooter genre (FPS), released between 2007 and 2019. The analysis is based on the identification of the stereotypical antagonistic representations. Its main attention is devoted to the ethnic and national stereotypes, because antagonists are ethnic and national Others in relation to protagonists. I aimed to define another summarizing and defining criterion of antagonistic representation, apart from the categories of othering already mentioned. In my thesis, I also describe ideological aspects which frame antagonistic representation. For the analysis of ideological content, I use Pötzsch's selective realism, which, by means of the four filters (violence, consequence, character and conflict) excludes negative and controversial aspects of war from FPS games. Not only does selective realism presents war selectively, it represents antagonistic actions selectively, too. In the text, I identify the stereotypical representations of three ethnic-national groups - orientalism and Cold War stereotypes in the case of Russians, neo-orientalism in the case of Middle Eastern antagonists and techno-orientalism in the case of East Asians. The ideology...