Siga este link para ver outros tipos de publicações sobre o tema: A Drugs.
Teses / dissertações sobre o tema "A Drugs"
Crie uma referência precisa em APA, MLA, Chicago, Harvard, e outros estilos
Veja os 50 melhores trabalhos (teses / dissertações) para estudos sobre o assunto "A Drugs".
Ao lado de cada fonte na lista de referências, há um botão "Adicionar à bibliografia". Clique e geraremos automaticamente a citação bibliográfica do trabalho escolhido no estilo de citação de que você precisa: APA, MLA, Harvard, Chicago, Vancouver, etc.
Você também pode baixar o texto completo da publicação científica em formato .pdf e ler o resumo do trabalho online se estiver presente nos metadados.
Veja as teses / dissertações das mais diversas áreas científicas e compile uma bibliografia correta.
1
Keesling, James Richard. "An evaluation of the drugs crime nexus, legalization of drugs, drug enforcement, and drug treatment rehabilitation". CSUSB ScholarWorks, 2000. https://scholarworks.lib.csusb.edu/etd-project/1697.
Texto completo da fonteResumo:
Law enforcement agencies are faced with the problem of how to reduce crime in the most economical method possible without violating the law. Since drug offenders also engage in a disproportionate amount of non-drug crime, then drug enforcement is considered as an acceptable general crime control method. Unfortuantely, this is an expensive option because incarcerating offenders is both costly and ony a short-term solution to the problem. A review of existing research examining the prior criminal histories of drug offenders compared to their previous involvement in violent and property crime is conducted to evaluate this relationship.
2
Osorio, Javier. "Hobbes on drugs| Understanding drug violence in Mexico". Thesis, University of Notre Dame, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3738644.
Texto completo da fonteResumo:
This dissertation analyzes the unprecedented eruption of organized criminal violence in Mexico. To understand the dynamics of drug violence, this dissertation addresses three questions. What explains the onset of the war on drugs in Mexico? Once the conflict starts, why does drug violence escalate so rapidly? And lastly, why is there subnational variation in the concentration of violence?
Based on a game theoretic model, the central argument indicates that democratization erodes the peaceful configurations between the state and criminal organizations and motivates authorities to fight crime, thus triggering a wave of violence between the state and organized criminals and among rival criminal groups fighting to control strategic territories. In this account, state action is not neutral: law enforcement against a criminal group generates the opportunity for a rival criminal organization to invade its territory, thus leading to violent interactions among rival criminal groups. These dynamics of violence tend to concentrate in territories favorable for the reception, production and distribution of drugs. In this way, the disrupting effect of law enforcement unleashes a massive wave of violence of all-against-all resembling a Hobbesian state of war.
To test the observable implications of the theory, the empirical assessment relies on a novel database of geo-referenced daily event data at municipal level providing detailed information on who did what to whom, when and where in the Mexican war on drugs. This database covers all municipalities of the country between 2000 and 2010, thus comprising about 9.8 million observations. The creation of this fine-grained database required the development of Eventus ID, a novel software for automated coding of event data from text in Spanish. The statistical assessment relies on quasi-experimental identification strategies and time-series analysis to overcome problems of causal inference associated with analyzing the distinct - yet overlapping - processes of violence between government authorities and organized criminals and among rival criminal groups. In addition, the statistical analysis is complemented with insights from fieldwork and historical process tracing. Results provide strong support for the empirical implications derived from the theoretical model.
3
Hernández, Yulán. "Drugs". Revista de Química, 2016. http://repositorio.pucp.edu.pe/index/handle/123456789/101299.
Texto completo da fonte
4
Dossou-Yovo, Flore. "Modification de la biodisponibilité orale des médicaments : interactions « Herb-Drugs » « Drugs- Drugs»". Thesis, Paris, CNAM, 2014. http://www.theses.fr/2014CNAM0936/document.
Texto completo da fonteResumo:
L’administration par voie orale des médicaments reste encore de nos jours la voie royale de la prise des médicaments car moins onéreuse et plus adaptée au confort du patient. Mais cette voie reste toujours inaccessible pour certains médicaments comme les médicaments biologiques et les bio similaires voir certains anticancéreux et antirétroviraux.Le but de ce travail est d’améliorer la biodisponibilité par voie orale des médicaments à faible biodisponibilité par la mise au point d’un promoteur d’absorption. Pour y arriver nous avons adopté comme stratégie de développer un promoteur qui agit à la fois sur le passage passif et sur le passage actif des médicaments. Les études in vitro ont été réalisées en chambre de perméation d’Ussing adaptées par la société Biomécatronics SAS (BéthuneFrance). Dans la première partie de ce travail (Brevet), nous avons montré que l’utilisation d’une composition pharmaceutique et/ou diététique comprenant un extrait de plante(Hibiscus sabdariffa) pouvait augmenter la biodisponibilité in vitro des médicaments et des xénobiotiques qui passent par la voie paracellulaire comme le cisplatine (21 fois),l’oxaliplatine (11fois), la fluorescéine isothiocyanate-Dextran 4000 (3 fois), mais également les médicaments connus pour leur transport actif par la voie transcellulaire comme l’Efavirenz (7 fois) et l’Atazanavir (4 fois). Dans la seconde partie de ce travail, nous avons cherché à vérifier si notre promoteur d’absorption des médicaments a un effet sur la couche de mucus intestinale.Cette couche peut être un facteur limitant de passage des médicaments au travers de la barrière intestinale.Dans un premier temps (article 1), nous avons induit l’augmentation de la couche mucus au niveau du colon de rat après un prétraitement pendant une semaine avec le métronidazole. Puis nous avions confirmé (article 2) que l’administration par voie orale de deux antibiotiques le Cotrimoxazole (CTX) et le métronidazole (MTZ) pendant une semaine augmente la couche de mucus au niveau du côlon ; aussi nous avons montré qu’il existe une relation entre l’augmentation de la couche de mucus et la diminution de la conductance qui est l’index de transport passif des ions, des électrolytes et de certaines molécules à faibles poids moléculaires.De plus l’augmentation de la couche de mucus au niveau de l’intestin est responsable de la diminution du passage transépithélial des deux antirétroviraux dont l’utilisation est recommandée en première ligne par l’OMS (le.Ritonavir et l’Atazanavir) surles sujets porteurs du VIH (virus de l’immunodéficience humain). Après les traitements auMTZ et au CTX la sécrétion de l’Atazanavir augmente respectivement dans le côlon proximal de 2 et 4 fois et dans le côlon distal de 3 et 5 fois. On obtient également une sécrétion du Ritonavir de 5 et 10 fois dans le proximal et de 2 et 5 fois plus dans le distal.Le travail se poursuit par l’étude de l’effet de notre promoteur d’absorption des médicaments sur la couche de mucus intestinal.En conclusion, ce travail montre que l’on peut augmenter la biodisponibilité in vitroen utilisant les promoteurs de l’absorption des xénobiotiques qui agissent à la fois au niveau du transport passif et actifOral dosing is still seen as the silver bullet of drug administration, as it is cheaper andbetter adapted to patient comfort. However, oral route is still inaccessible to many drugssuch as biologics and biosimilars respectively certain anticancer drugs and antiretrovirals(ARV).The aim of this present study was to find new drugs enhancers that improve the oralbioavailability of drugs and xenobiotics. All the studies were realized in vitro using Ussingchambers technic. To achieve the set objective we used the strategy to develop drugenhancer which can modulate at the same time transcellular and paracellular pathways.In the first part of this study (patent) we have shown that the use of a pharmaceutical and /or a dietetic formulation containing a plant extract (Hibiscus sabdariffa) could increase thebioavailability in vitro in rats not only of cisplatin (21 fold), oxaliplatin (11 fold) andFluorescein Isothiocyanate-Dextran 4000 (FD4, 3 fold). All that drugs were transportedthrough intestinal barrier using paracellular pathway. In addition the study showed thatthis formulated enhancer can increased the bioavailability of Efavirenz (7 fold) andAtazanavir (4 fold) which are active transported.In order to assess the effect of new drugs enhancer on mucus thickness that limits thetransport of xenobiotic through intestinal barrier, we decide to evaluate his effect on passiveand active transport of drugs.In the second part of this study we have shown that after a week of pre-treatment of ratswith Metronidazole (MTZ, publication 1) and Cotrimoxazole (CTX, publication 2), the twomost commonly used antibiotics in the prophylaxis against opportunistic infections in HIV /AIDS, both increase colonic mucus thickness that affect directly passive intestinalpermeability by reducing conductance an index of passive transport through intestinalepithelium. In addition those antibiotics also entail a change in the transepithelialconductance and ARV fluxes. After MTZ and CTX treatment the secretion of Atazanavir(ATZ) increases respectively in the proximal colon by 2 to 4 fold and in the distal colon by 3to 5 fold respectively. Ritonavir (RTV) is poorly absorbed in control, after a week of pretreatmentwith MTZ and CTX one rather notices a secretion of RTV 5 to 10 fold higher in theproximal and 2 to 5 fold higher in the distal colon. The next study will be conducted toevaluate the effect of new drugs enhancer on mucus thickness layer.In conclusion, oral bioavailability of drugs and xenobiotics can be enhanced bypharmaceutical composition that contains herbal extract which increase passive and activetransport of drugs through intestinal barrier
5
Rosenbaum, Erik. "Optical characterization of potential drugs and drug delivery systems". Doctoral thesis, Umeå universitet, Kemiska institutionen, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-40177.
Texto completo da fonteResumo:
This Thesis is a characterization study on substances having potency as drugs as well as on a lipid based drug-delivery matrix. The optical properties of newly synthesized molecules with proven pilicide properties have been characterized with several spectroscopic methods. These methods include optical absorption and fluorescence as well as time-resolved fluorescence. Upon covalently linking compounds with high quantum yields of fluorescence to specific parts of the pilicide, the biological impact was found to increase for some of the derivatives. Furthermore, by expanding the aromatic part of the pilicide molecule, a significant increase in the inherent fluorescence was obtained. The S0-S1 absorption band for these molecules was found to originate from an impure electronic transition, vibronically promoted by intensity borrowing from higher electronic states. Included in this Thesis is the measurement of how deeply some in this class of newly synthesized molecules become situated when placed inside ganglioside GM1 micelles, and how the molecules’ reorientation is affected. By means of radiation-less energy transfer, it was shown that the molecules place themselves close to the hydrophobic-hydrophilic interface inside the GM1 micelles. As a consequence they are exposed to a densely packed environment, which inhibits the free tumbling of the molecule. This restricted tumbling could be measured by means of time-resolved depolarization experiments. The release of drug-like fluorescent molecules is investigated from a lipid mixture, which upon equilibrium with water forms a mixture of inverted hexagonal and cubic phases. The lipid matrix displayed an extended release over the course of weeks, in vitro, for molecules having a large variation in hydrophobicity.
6
Attardo, Giorgio G. (Giorgio Giovanni). "Drug design and synthesis of novel heteroanthracycline antitumor drugs". Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74641.
Texto completo da fonteResumo:
Novel heteroanthracycline antitumor drugs were designed based on structure activity relationship studies and known mechanisms of drug action. Their preparation required the development of a general synthetic approach.After extensive studies, three methodologies were developed for the general synthetic plan. The first method involved photoenolisation of 2,5-dimethoxybenzaldehyde and SO$ sb2$ entrapment of the o-quinodimethane to give 4,7-dimethoxy-1-hydroxy-1,3-dihydrobenzo(2,3-c) thiophene-2,2-dioxide. This compound served as a general intermediate towards the synthesis of several heteroanthracyclinones. It could be reduced to the oxathiin-2-oxide derivative which thermally extruded SO$ sb2$ to yield the o-quinodimethane. Reentrapment of this latter intermediate with various glyoxalates gave key isochroman derivatives. The second method is an improvement over the first. Isochromandiones with a C-1 hydroxyl functionality were prepared from oxidative demethylation of 1-hydroxyisochromans. These were obtained after acid hydrolysis of the coupling products between epoxides and the cuprate of 2,5-dimethoxy-6-methylbenzaldehydedioxane acetal. The third method involved a sequential cycloaddition routine with two o-quinodimethanes.
By combining newly developed techniques with known methods, a general synthetic plan was developed. Consequently, the total synthesis of six tetracyclic structural hybrids of the naphthoquinone(2,3-c) pyranyl class of antibiotics was accomplished; along with the total synthesis of (R) and (S) 1-(4$ sp prime$-O-p-nitrobenzoyl-N-trifluoroacetyldaunosamine)-$ 1,3$-dihydrothioxantho(2,3-c) thiophene-2,2-dioxide, p-nitrobenzyl(5,12-dihydroxy-3,4-dihydrothioxantho(2,3-c) and (3,2-c) pyran-3-yl)formate, and eight novel heteroanthracyclines with the 5,12-dioxo-2,3,5,12-tetrahydroanthraceno(2,3-c) pyranyl backbone. The diastereomeric mixture of (1$ sp prime$S, 1R, 3S) and (1$ sp prime$S, 1S, 3R) methyl(11-hydroxy-1-$(2 sp prime,3 sp prime,6 sp prime $-trideoxy-3-trifluoroacetamido-L-lyxohexopyranose)-$5,12 $-dioxo-3,4,5,12-tetrahydroanthraceno(2,3-c) pyran-3-yl) formate was found to possess equipotent antileukemic activity to doxorubicin with no cross resistance.
7
Hill, John C. "DRUMMING AWAY DRUGS: AN INNOVATIVE ALTERNATIVE TOWARDS DRUG REHABILITATION". UKnowledge, 2014. http://uknowledge.uky.edu/cld_etds/14.
Texto completo da fonteResumo:
Drug use poses a serious threat to the quality of life for many Kentuckians and their families. Recent statistics indicate drug offenders account for a significant portion (in one year, 52,597 arrests were made for drug violations statewide) of individuals within thecriminal justice system, directly affecting the economic vitality within our state (Bunn & Slavova, 2012; Federal Bureau of Investigation, 2012). These statistics signify an overwhelming need for effective prevention efforts and innovative treatment alternatives. This study provides an innovative alternative treatment for drug offenders that infuses social and emotional coping strategies using percussion as a context. During the innovative program participants were able to express, recognize, articulate and evaluate themselves and their peers’ emotional coping strategies while developing peer camaraderie. They did so while being introduced to rudimentary drumming skills, fusing emotional intelligence with the art of drumming. The hypothesis is that this innovative program will enhance participant emotional intelligence to express, learn an effective coping skill, and establish camaraderie with their peers.
8
Hemingway, Judith Frances Mary. "Spatializing drugs discourses : cultural geographies of illicit drug-using". Thesis, University College London (University of London), 2003. http://discovery.ucl.ac.uk/10020432/.
Texto completo da fonte
9
Mohiddin, Syed Basha. "Development of novel unsupervised and supervised informatics methods for drug discovery applications". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1138385657.
Texto completo da fonte
10
Nissen, Lisa Monique. "Quality use of medicines : from drug use evaluation to rural community pharmacy practice /". St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16549.pdf.
Texto completo da fonte
11
Tayob, Shamima. "Challenges in the management of drug supply in public health centres in the Sedibeng District, Gauteng Province". Thesis, University of Limpopo (Medunsa Campus), 2012. http://hdl.handle.net/10386/683.
Texto completo da fonteResumo:
Thesis (MSc(Med)(Pharmacy))--University of Limpopo, 2012.ABSTRACT South Africa, 80% of the population is dependent on the vernment to provide for their health care needs, mainly ugh primary health care facilities. In the health objectives of the National Drug Policy, the government of South Africa outlines its commitment to ensuring availability and accessibility of medicines which are effective, affordable, safe and of good quality in all sectors of the health care system ( N a t ion a IDe par t men t of He a It h, 1 996) . In o rd e r to assess the availability of d ru g s and identify ch a II en g e s w hi c h . ex is tin the Emf u Ie n i sub - d is t r i c t wi t hi nth e Sedibeng district, a questionnaire was administered to 21 primary health care facility managers/store managers, fo u r Community Health Centre managers and five transport officers in the district. In addition, a document review process was conducted to verify aspects of th e facility managers' and store managers' responses. Bin cards and primary health care order files were also examined in conjunction with a checklist to establish whether stock control systems were in place. There was a 100% response with all primary health care centres and community health care centres completing th e questionnaires. It was established that drugs at primary and community health care clinics were procured from the Sedibeng district pharmacy. In each of these clin ics there were specific individuals responsible for medicine supply management. Only four primary health care clinics had full-time pharmacist assistants employed, and 14 clinics were visited by the assistants on a weekly/bi-weekly basis. There were no employees that have received training in drug supply management in the last 12 months in 88% of the clinics interviewed. Nineteen clinics claimed that the storage area was not large e n 0 ugh to s tor e a II the s toe k f or a m 0 nth's sup ply and 0 n I yon e clinic had a secure delivery area for their medication. It was established that 24 facilities received stock by two specific procedures namely; that the number of boxes were checked and the driver's note was then signed, and stock received was checked against the invoice. Of the interviewed cl i nics, 20% admitted that the re-order level had not been calculated for all tracer items in the store. Standard Operating Procedures, Standard Treatment Guidelines and the Essential Drugs List were also not available at all facilities. The results indicate inadequacies and weaknesses in procurement, quantification, stock control, storage and record keeping. It clearly demonstrates that inadequately-trained staff was a ma j 0 reo n t rib uti n g fa c tor to d rug s h 0 r tag e s. The r e was a I a c k 0 f monitoring and evaluation by th e district pharmacy as pharmacists did not manage to visit all the clinics each month. Most of the inadequacies and weaknesses can be addressed at facility level with pro per supervision, in-service training, mentoring and support of staff and the reinforcement of drug supply management training. Regular supervisory visits together with updating the monitoring too I in terms of th e problems identified will improve th e management of drugs and ultimately decrease the number of out of stocks where problems have been identified at primary health care level.
12
Zhang, Huarui. "Design, synthesis and activity evaluation of novel exosome inhibitors". HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/849.
Texto completo da fonteResumo:
Background: Exosomes are extracellular vesicles (EVs) that produced in the endosomal compartment of most eukaryotic cells, and have observed increasing attentions over the past decades. They play important roles in cell- to-cell communications, they can carry varieties of substances, like proteins, nucleic acids and lipids, to the target cells they encounter. These cargos could influence the function of recipient cells. This novel mode of intercellular communication is found to be of critical importance to many cellular activities. However, exosomes are involved in various diseases processes. Tumor- derived exosomes could promote cancer progression, and our preliminary study indicated that exosome released from osteoclasts could inhibit bone formation. We also found that osteoarthritis (OA) progression in OA mice could be attenuated by inhibiting exosomes released by osteoclasts. Therefore, inhibition of exosome release has potential value in the treatment of diseases. The exosome release is under control by RAB27A, which is a protein involved in protein transport and signal transduction. It is reported that a compound named Nexinhib20 could selectively inhibit RAB27A, but this compound is highly toxic to RAW264.7 cells, which IC 50 is 1.5 µM. Therefore, for safety concerns, it has to be chemically modified to reduce toxicity. Aim: (1) To design and synthesize a series compounds based on the structure of Nexinhib20. (2) To evaluate the toxicity and exosome inhibiting activity of the synthesized compounds and discuss the structure-activity relationships (SAR) of them. Materials and Methods: Nexinhib20 derivatives were synthesized by aldol reaction. The cytotoxicity of these compounds was evaluated by MTT assay. The exosome inhibiting activity of these compounds was evaluated through exosome isolation and quantitation. Result: A series of compounds were synthesized and their structures were confirmed by LC-MS and NMR. The structure-activity relationships of these compounds were discussed, and the results showed that compounds A3, A23 and B2 exhibited lower toxicity compared to Nexinhib20 and strong exosome inhibiting ability. Conclusion: The results of this project indicate that A3, A23 and B2 exhibited low toxicity and good exosome inhibiting activity. Based on this, further chemical modification could be applied to develop new exosome inhibitors with better efficacy
13
Hartmann, Neil Godfried. "Intercalative drugs in cancer chemotherapy : two approaches towards drug development". Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292983.
Texto completo da fonte
14
Kaza, Lakshmi S. "Novel Thermal Analytical Techniques to Characterize Drugs and Drug Delivery". Cleveland State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=csu1317258017.
Texto completo da fonte
15
Kigen, Gabriel Kimutai. "Assessment of Drug Interactions Between Antiretroviral and the Anthelminthic drugs". Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507508.
Texto completo da fonte
16
McCallum, Emma Clare. "Adaptive phase II clinical trial design using nonlinear dose-response models". Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709013.
Texto completo da fonte
17
Carroll, Steven M. McGuire Marvin H. "The economics of the drug war : effective federal policy or missed opportunity? /". Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2002. http://library.nps.navy.mil/uhtbin/hyperion-image/02Jun%5FCarroll%5FMcGuire.pdf.
Texto completo da fonte
18
Tooley, Jennifer. "Demon drugs and holy wars, Canadian drug policy as symbolic action". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ54654.pdf.
Texto completo da fonte
19
Wheeler, Daniel Wren. "Weakened by strengths : drugs in solution, medication error and drug safety". Thesis, University of Oxford, 2008. http://ora.ox.ac.uk/objects/uuid:238087a5-120b-4a3d-9437-5840cecf8b6a.
Texto completo da fonteResumo:
The concentrations of some drug solutions are often expressed as ratios or percentages. This system simplified prescription and dispensing when Imperial measures such as grains and minims were used. Ampoules of powerful vasoactive drugs such as catecholamines and potentially toxic local anaesthetics are still labelled as ratios and percentages, seemingly through habit or tradition than for any useful clinical reason. This thesis argues that adherence to this outdated system is confusing, causes drug administration errors, and puts patients at risk. Internet-based questionnaires were used to quantify medical students’ and doctors’ understanding of ratios and percentages. A substantial minority of almost 3000 doctors could not convert between ratios, percentages and mass concentration correctly, made dosing errors of up to three orders of magnitude in written clinical scenarios, and struggled with conversions between metric units. These findings are strong arguments for expressing drug concentrations as mass concentration and providing better drug administration teaching. High fidelity patient simulation was used to examine the influence of clearer ampoule labelling and intensive drug administration teaching. This allowed critical incidents to be reproduced realistically, clinical performances to be assessed, and outcome measures to be accurately recorded. Randomised controlled trials were conducted that demonstrated positive influences of both interventions for doctors and students. The difficulties that nurses encounter when preparing infusions of these drugs on critical care units were also studied and are reported. The findings presented should be sufficient to persuade regulatory authorities to remove ratios and percentages from ampoule labels – a straightforward, cheap, commonsense intervention. The lack of effective clinical error reporting systems and the extreme practical difficulties of conducting clinical trials in this field mean that a firm link between this intervention and patient outcome is unlikely ever to be made, but this should not be an excuse for maintaining the status quo.
20
Banks, Simon. "Incompatibilities between HPMC and model drugs : consequences for extended drug release". Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421473.
Texto completo da fonte
21
Javaheri, Hoda. "Wet granulated liquisolid drug delivery systems with hydrophobic and hydrophilic drugs". Thesis, University of Sunderland, 2017. http://sure.sunderland.ac.uk/8549/.
Texto completo da fonteResumo:
The formulation of hydrophobic drugs into appropriate dosage forms is challenging due to the problems associated with those drugs such as low solubility and poor dissolution. Using a liquisolid system is a promising method to improve the dissolution of hydrophobic drugs and in sustaining the release of hydrophilic drugs, in which solid drugs are dispersed in non-volatile liquid vehicles. The aim of this research was to use the liquisolid technique to enhance the dissolution rate of glibenclamide, a model hydrophobic drug, and to sustain the release of metformin-HCl, as a model hydrophilic drug. The wet granulation process was applied to liquisolid powders with the aim of overcoming issues of poor powder flowability and compressibility, especially using high viscosity liquid vehicles. This process was performed with liquisolid powders prior to compaction into tablets. Different liquisolid formulations were prepared using three liquid vehicles (polyethylene glycol400 (PEG® 400), Synperonic® PE/L44 and Cremophor® ELP), at 10 and 30 % w/w drug concentrations for glibenclamide; and 30% and 60% w/w drug concentrations for metformin-HCl. Avicel®PH102 was used as a carrier, whilst colloidal silicon dioxide was employed as a coating material to convert the wet mixtures into dry powders. Potato starch, 5% w/w, as a disintegrant was blended with the mixtures manually for 10 minutes and then 0.75% of magnesium stearate as a lubricant was added and mixed for 5 minutes. The final powder (depending on its flowability and compactability) was then compacted automatically using a single-punch tableting machine to give tablets with 4 mg for glibenclamide and 40 mg for metformin-HCl. Prepared liquisolid compacts were characterized by using British Pharmacopeia quality control tests: uniformity of weight, friability, disintegration, hardness and drug dissolution. iii It was found, for both drugs, that by application of wet granulation to liquisolid powder admixtures, the large-scale production of liquisolid compacts is feasible, which can be easily adapted to the pharmaceutical industry. In addition to enhancing the flowability and compressibility of the powders, the glibenclamide dissolution was also improved due to the enhanced binding of particles and because of the wetting effect of liquid vehicles on the hydrophobic drug, which make the drug more available for dissolution. For the sustained release preparations of liquisolid metformin-HCl, hydroxyl propyl cellulose (HPC) was used as a novel carrier in liquisolid compacts. The results showed 92% drug release after 12 hours using Cremophor®ELP (with 30% w/w drug concentration) which was the best sustained drug release formulation. Additionally, Eudragit® RL30D and Eudragit® RLPO have been used to study their effects on drug release from liquisolid formulations, examining if they can sustain or give more rapid drug release. Both types of Eudragit revealed immediate release with metformin-HCl rather than sustained drug release, with the tablets disintegrating within seconds. This suggests formulating orodispersible metformin-HCl tablets using Eudragit® RL30D as a liquid vehicle. In summary, liquisolid technology has led to promising results, not only in enhancing the drug dissolution of hydrophobic drugs, but also in sustaining and promoting the release of hydrophilic drugs.
22
Wang, Shining. "DRUG DEVELOPMENT OF TARGETED ANTICANCER DRUGS BASED ON PK/PD INVESTIGATIONS". Diss., Temple University Libraries, 2008. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/2535.
Texto completo da fonteResumo:
PharmaceuticsPh.D.
EGFR inhibitors, such as gefitinib, are examples of targeted anticancer drugs whose drug sensitivity is related to gene mutations that adds a pharmacogenetic [PG] dimension to any pharmacokinetic [PK] and pharmacodynamic [PD] analysis. The goal of this project was to characterize the PK/PD properties of gefitinib in tumors and then apply these results to design rational drug design regimens, and provide a foundation for future studies with EGFR inhibitors. Progressions of in vitro and in vivo studies were completed to understand the PK and PD behavior of gefitinib. In vitro cytotoxicity assays were first conducted to confirm the gefitinib sensitivity differences in a pair of human glioblastoma cell lines, LN229-wild-type EGFR and LN229-EGFRvIII mutant, an EGFR inhibitor-sensitizing mutation. Subsequent in vitro PD studies identified phosphorylated-ERK1/2 (pERK) as a common PD marker for both cell lines. To describe the most salient features of drug disposition and dynamics in the tumor, groups of mice bearing either subcutaneous LN229-wild-type EGFR or LN229-EGFRvIII mutant tumors were administered gefitinib at doses of 10 mg/kg intravenously (IV), 50 mg/kg intraarterially (IA) and 150 mg/kg orally (PO). In each group, gefitinib plasma and tumor concentrations were quantitated, as were tumoral pERK. Hybrid physiologically-based PK/PD models were developed for each tumor type, which consisted of a forcing function describing the plasma drug concentration-profile, a tumor compartment depicting drug disposition in the tumor, and a mechanistic target-response PD model characterizing pERK in the tumor. Gefitinib showed analogous PK properties in each tumor type, yet different PD characteristics consistent with the EGFR status of the tumors. Using the PK/PD model for each tumor type, simulations were done to define multiple-dose regimens for gefitinib that yielded equivalent PD profiles of pERK in each tumor type. Based on the designed PK/PD equivalent dosing regimens for each tumor type, gefitinib 150 mg/kg PO qd × 15 days and 65 mg/kg PO qd × 15 days multiple-dose studies were conducted in wild-type EGFR and EGFRvIII mutant tumor groups, respectively. In each tumor group, gefitinib plasma and tumor concentrations were measured on both day 1 and day 15, as were tumoral amounts of pERK. Different from single-dose model simulations, gefitinib showed nonlinear PK property in the wild-type tumor due to the down-regulation of membrane transporter ABCG2. Moreover, acquired resistance of tumoral pERK inhibition was observed in both tumor types. Nevertheless, gefitinib had an analogous growth suppression action in both tumor groups, supporting the equivalent PD dosing strategy. Overall, single-dose gefitinib PK/PD investigations in a pair of genetically distinct glioblastomas facilitated the development of hybrid physiologically-based PK/PD models for each tumor type, and further introduced a novel concept of PK/PD equivalent dosing regimens which could be applied in novel drug development paradigms. Preliminary multiple-dose gefitinib studies revealed more complex PK/PD characteristics that needed to be further explored.
Temple University--Theses
23
Naina, Mohamed Isa. "Novel approaches to pharmacovigilance : exploiting routinely acquired healthcare data". Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=165979.
Texto completo da fonteResumo:
Introduction: The main pharmacovigilance system in the United Kingdom is the ‘Yellow Card’ spontaneous reporting system which suffers from low reporting rate, and long lag time between drug launch and ADR recognition. Aim: The aim of this study is to develop a pharmacovigilance system to permit the early detection of adverse drug reactions using routinely acquired NHS health data with minimal cost and resources. Methods: There are 2 methods for this study; Phase 1: The extraction of drug persistence data from routinely acquired NHS health data, and Phase 2: Identifying the exact reason(s) for patient discontinuation of drug therapy within 6 months of the index prescription. Results: Phase1: During the study period 4243 patients were initiated on ramipril, 8849 patients on simvastatin, 3242 patients on ARBs, 3646 patients on amlodipine and 269 patients on lercanidipine. The 1, 2-3 and 4-6 month discontinuation rates were 9.9%, 4.9% and 4.2% respectively for ramipril, 9.5%, 3.4% and 3.2% for simvastatin, 8.7%, 2.9% and 2.5% for ARBs, 16.2%, 6.3% and 4.8% for amlodipine, and 17.8%, 3.7% and 3.7% for lercanidipine. Drug discontinuation rates determined agree closely with published data from trials and post marketing surveys in terms of the peak time at which ADRs and discontinuations occur (1 month), the populations most frequently affected (females and the young or elderly depending on drug), and the relationship between the frequency of ADRs and discontinuations relative to the drug of interest, especially for antihypertensive (CCBs>ACEIs>ARBs). Phase 2: Six (20%) of 30 participating primary care practices, contributing to the PTI database, agreed to be approached directly. Completed data was returned for 98% of patients whom discontinued amlodipine due to a specific ADR. Conclusions: Drug discontinuation rates obtained from health care databases is a good surrogate for ADR/E rates. Specific reasons for discontinuation, such as adverse drug reactions, can be identified directly from such electronic databases or more effectively from the primary care medical records held in primary care practices.
24
Chan, Kin-yi Ivy. "A study of determinants of relapse in psychotropic substance abuse /". Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19470757.
Texto completo da fonte
25
Bartu, Anne E. "A grounded study of the experience of detoxification from psychoactive drugs". Curtin University of Technology, School of Nursing, 1998. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=12124.
Texto completo da fonteResumo:
The main objective of this thesis was to develop a substantive theory that explained the phenomenon of detoxification from psychoactive drugs such as alcohol, tranquillisers, opioids, and amphetamines in a medical treatment unit for licit and illicit drug users. The other objectives were to (a) determine if the differences reported in earlier studies between licit and illicit drug users in terms of socio-demographic and drug use variables remain extant, and (b) assess the extent of minor psychiatric morbidity among the participants. Both grounded theory and quantitative methods of data collection and analysis were used in the study.The findings of the quantitative component of the study indicated that there were significant differences between licit and illicit drug users in regard to age, drug use characteristics, and completing the treatment program. That is, illicit drug users were younger than licit drug users, more likely to be poly drug users, and drop out of the program. The prevalence of minor psychiatric morbidity among the participants was 93.6%, and was largely independent of socio-demographic and drug use variables. The high prevalence of minor psychiatric morbidity suggests that the majority of participants warranted further follow-up support in the community after they left the treatment unit. The uptake of referrals for follow-up support, however, was 55.9%.The basic or core social psychological problem identified by the constant comparative method of grounded theory was found to have two parts, both of which were interpreted as forms of disequilibrium. The first part of disequilibrium, which was a precursor to treatment, was conceptualised as Hitting the Wall. The events associated with the symbolic "wall" interrupted the participants' drug focussed lifestyles and induced them to enter treatment. These events and problems were not resolved whilst in ++treatment, they lingered with the participants while they were in the unit, and remained to be addressed when they left. Whilst undergoing detoxification the participants encountered the second part of disequilibrium which was categorised as Incompatibility. The problem of Incompatibility was related to the heterogeneity of the participants and the structure of the treatment program that in many cases was unable to accommodate individual differences and needs.The core or basic social psychological process was conceptualised as Seeking Balance through Hanging In. The participants engaged in this process to deal with the disequilibrium of the precursor problem of Hitting the Wall and the problem of Incompatibility encountered in the unit. Seeking Balance through Hanging In was found to have four phases. The phases were Making the Break, Submitting to Cleansing, Fitting In, and Moving On. The process was linear in that the phases were sequential, and failure to complete a phase meant dropping out of the detoxification program. The experience of detoxification was modified by several contextual conditions. These were the physical enviroment, the participants' expectations of withdrawal symptoms, and the workload of the staff.The substantive theory, Seeking Balance through Hanging In, integrated all emergent categories, and explained the experience of the phenomenon of withdrawal from psychoactive drugs in a particular context. Recommendations for further research include testing the described phases and relationships of the substantive theory in similar environments, exploring the importance of the modifying conditions on client outcomes, and undertaking follow-up studies to determine the outcomes of those who completed the program as compared to the outcomes of those who dropped out. In addition, further studies are recommended to assess the transientness of the level ++
of minor psychiatric morbidity detected among the participants in this study.The findings of this study make an important contribution to understanding the experience of detoxification from the perspective of the participants. The substantive theory has implications for clinical practice, professional education, management, and further research.
26
Yeh, Teng-Kuang. "Pharmacokinetics of anti-aids and anti-cancer drugs : implications on drug delivery and drug interaction /". The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu148654688938101.
Texto completo da fonte
27
Mavridis, Lazaros. "High throughput virtual drug screening using spherical harmonic molecular surface representations". Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=25936.
Texto completo da fonte
28
Soane, Robert J. "Bioadhesive polymers as intranasal drug delivery systems for peptide and protein drugs". Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298078.
Texto completo da fonte
29
Coomber, Ross. "Perceptions of illicit drugs and drug users : myth-understandings and policy consequences". Thesis, University of Greenwich, 1999. http://gala.gre.ac.uk/8648/.
Texto completo da fonteResumo:
This submission to the University of Greenwich for a Ph.D. by published works is composed of ten peer-reviewed articles, five book chapters, and one journal editorial. The earliest publication is dated from 1992 while the two most recent articles have been formally accepted for publication and are to be published in the near future. The pieces, to aid coherence, are not arranged in strict chronological order but rather in an order best able to demonstrate coherence and theme. The central theme running through these published works relates to the ways that drugs, drug users, and the activities which surround them are often subject to exaggeration, distortion and untruths and that drug control policy, rather than being rationally based is often the result of fear, prejudice and unreason. The core of the submission, eight papers researching the dangerous adulteration of illicit drugs, reflects these issues strongly. An area almost untouched by social science prior to this research these papers represent an attempt to pull together a range of evidence to inform more fully about drug adulteration practices. A wide range of methods, including a relatively innovative approach to researching hard to reach groups via the Internet and World Wide Web were employed. Almost all of the findings are at odds with what is commonly and professionally (drugs field) assumed to happen as regards the adulteration/dilution of illicit drugs. The other contributions all reflect similar concerns but are focussed on other drug related areas. Each piece is preceded by a short contextualising introduction. The appendices include a complimentary unpublished paper on drug adulteration, the preface to one of two books to which I was sole editor, some shorter contributions to drug field publications which, whilst widely read are less academic in their tone and approach, and two publications which represent the culmination of earlier joint research on drug policy.
30
Sostelly, Alexandre. "Mechanistic model-based drug development in the management of anticancer drugs resistance". Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10203.
Texto completo da fonteResumo:
La résistance aux chimiothérapies anticancéreuses constitue un problème majeur dans la prise en charge du cancer. Les transporteurs d'efflux contribuent à ce phénomène de résistance en altérant l'accumulation intracellulaire des cytotoxiques. Dans le passé, l'inhibition du transporteur d'efflux P-gp n'a pas permis de surmonter ce phénomène notamment à cause du manque de méthodes adéquates pour identifier et quantifier la pharmacologie des inhibiteurs d'efflux. Récemment de nouveaux inhibiteurs de BCRP, l'un des derniers transporteurs d'efflux découverts, ont été synthétisés permettant de retester l'intérêt de l'inhibition de ces transporteurs dans la prise en charge de la résistance aux anticancéreux. Néanmoins, afin d'éviter les mêmes écueils que lors du développement des inhibiteurs de P-gp, il est nécessaire d'utiliser d'autres approches telles que la modélisation mathématique dès le début du développement préclinique de ces inhibiteurs. Cette thèse a pour but de montrer les bénéfices de la modélisation et de la simulation dans le développement préclinique des inhibiteurs de transporteurs d'efflux et plus largement dans le développement des molécules anticancéreuses. L'exemple utilisé au travers de ce travail concerne l'étude de l'interaction entre l'irinotecan, un cytotoxique largement utilisé dans le traitement du cancer colorectal, et le MBLI87, un nouvel inhibiteur de BCRP. Deux principaux axes ont été abordés dans ce travail : - Le développement de modèles (semi-) mécanistiques à effets mixtes pour identifier et quantifier les facteurs impactant l'efficacité de la combinaison irinotecan-MBLI87 - Le développement de modèles d'inhibition de la croissance tumorale à effets mixtes pour évaluer précocement ce type d'interaction de traitements et pour optimiser la réponse tumorale. Les résultats obtenus avec l'approche de modélisation ont permis d'identifier certains des mécanismes tumoraux impactant l'efficacité des inhibiteurs de transporteur d'efflux. De plus cette approche s'est révélée supérieure aux approches classiques dans l'évaluation de ces molécules et dans l'optimisation de la réponse tumorale démontrant la puissance de la modélisation et de la simulation comme outil de développement des molécules anticancéreusesAnticancer drug resistance is a major issue in the management of cancer disease. Efflux transporters contribute to the multidrug resistance by altering the intracellular disposition of cytotoxic drugs. In the past, the inhibition of P-gp efflux transporter essentially failed because of the lack of adequate methods to identify their mechanisms of action. Recently, new inhibitors of BCRP, one of the latest efflux transporter that have been discovered, have been developed that allow re-testing the multidrug resistance inhibition through efflux inhibition. Nevertheless, to avoid the same issues of development as for P-gp inhibitors, new methods have to be used. This PhD work aims to demonstrate the benefits of mechanistic models to support the development of efflux transporter inhibitors and more generally of oncology compounds through two axes: - The development of mechanistic models of the interaction between cytotoxic and efflux transporter inhibitors - The development of quantitative tumour growth inhibition models to early evaluate oncology compounds and optimize patients’ response The results obtained with this approach allow the identification of key mechanisms of efflux transporter inhibitors and demonstrate the power of modelling and simulation to support oncology drug development
31
Moorad, Razia. "Computer-aided drug design and the biological evaluation of anti-cancer drugs". Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20715.
Texto completo da fonteResumo:
Computer-aided drug design has become a promising alternative to high-throughput screening by identifying potential hits in silico for in vitro evaluation. In this study a combination of ligand-based and structure-based virtual screening was performed to identify in silico hits. This was based on finding similar inhibitors to 6-amino-4-(4-phenoxyphenylethylamino) quinazoline, a potent inhibitor of the Nuclear Factor kappa B (NF-κB), a transcription factor that has a pivotal role in cancer survival and Pentamidine, an anti-parasitic drug that has recently been demonstrated to possess tumour-killing activity. A hierarchical methodology consisting of a similarity search followed by structure-based virtual screening of the ZINC database was performed. In order to perform the docking studies, binding sites for 6-amino-4-(4-phenoxyphenylethylamino) quinazoline on the NF-κB/IκBα complex were identified through blind docking. In addition, the National Cancer Institute (NCI) database was screened, utilising existing structure-activity relationship data from literature. A pharmacophore search was designed to test the hypothesis of the structural features necessary for activity as seen with quinazoline inhibitors of NF-κB. No virtual hits from the ZINC database were confirmed with in vitro activity. On the other hand, three compounds identified from the pharmacophore search were confirmed to inhibit cancer cell proliferation in vitro, with compound NSC727152 demonstrating the most potent activity. In order to determine if NSC727152 acted similarly to 6-amino-4-(4-phenoxyphenylethylamino) quinazoline by inhibiting NF-κB, the effects of NSC727152 on the expression of NF-κB targeted genes, including the Growth Arrest and DNA Damage 45 (GADD45) α and γ and the Interleukin 6 (IL-6) genes were evaluated. GADD45 α and γ have been shown to be regulated by NF-κB during cancer progression and aberrant IL-6 gene expression has been implicated in cancer progression and mortality and its expression is at least partially mediated via constitutive activation of NF-κB. In this study, it has been demonstrated that GADD45 α and γ are upregulated after treatment with NSC727152. A down-regulation of the IL-6 promoter activity and mRNA expression in cancer cells treated with NSC727152 has also been demonstrated in this study. However, no hits similar to Pentamidine were confirmed with in vitro activity. In conclusion, the compound NSC727152 has been shown to inhibit NF-κB and further analysis is necessary to determine its full potential as an NF-κB inhibitor.
32
Kola-Mustapha, Adeola Tawakalitu. "Novel biomimetic polymeric nanoconjugates as drug delivery carriers for poorly soluble drugs". Thesis, De Montfort University, 2013. http://hdl.handle.net/2086/10243.
Texto completo da fonteResumo:
Active Pharmaceutical Ingredients with poor solubility have presented significant difficulties in drug product design and development including slow and ineffective absorption leading to inadequate and variable bioavailability. Therefore it has become increasingly desirable to overcome the low aqueous solubility of drug candidates and develop more novel and innovative formulation approaches to increase the dissolution rate of the poorly soluble drugs. This work focuses on the formulation of novel amorphous ibuprofen-polymer nanoconjugates based on the polymer-drug complexation in order to improve its physical and dissolution characteristics without the use of toxic organic solvents. Plain and ibuprofen-loaded binary and ternary nanoconjugates were prepared using four modified co-precipitation techniques including melt solubilization; alkaline solubilization; surfactant solubilization and hydrotropic complexation techniques. A remarkably high loading capacity was achieved ranging from 89.05 to 99.49% across the four techniques and polymer-polymer ratio of 50:50 was found to be most efficient. All the four techniques reduced the size of ibuprofen (2.87 μm) significantly in the presence of 2.0 x10-3 mM of Diethylaminoethyl Dextran (DEAE-Dextran) in the order melt solubilization (203.25 nm) > alkaline solubilization (185.68 nm) > surfactant (Tween 80) solubilization (122.17 nm) > hydrotropic complexation (77.92 nm). 5.0 x 10-4 mM of chitosan also reduced the size of ibuprofen from 2872.12 to 10.70 nm (268-fold reduction). The FTIR spectroscopic analysis revealed electrostatic, hydrophobic and hydrogen bonding interaction between solubilized ibuprofen and the cationic polymers (DEAE-Dextran and chitosan) to form a new product (an amide). Polymer-polymer complexation also occurred between DEAE-Dextran and gellan as well as chitosan and gellan to a different extent depending on the mixing ratios. 1H and 13C NMR analysis confirmed the conjugation between ibuprofen and each of the cationic polymers as well as the formation of a new amide product. DSC thermal analysis showed that the nanoconjugates exhibited new broad and diffuse peaks confirming that they did exist in amorphous state as multiple complexes. The TGA thermograms of the binary nanoconjugates exhibited one step degradation profile compared with the physical mixture which exhibited two steps. However the ternary nanoconjugates exhibited two steps degradation profile confirming the formation of multiple complexes. Marked enhancement of drug release was achieved by the four techniques compared with the ibuprofen control. All the DG (DEAE-Dextran - Gellan) complexes exhibited a higher release profile than ibuprofen control. Fickian and non-Fickian anomalous mechanisms were deduced for the drug release of ibuprofen from the binary conjugates. The ternary nanoconjugates exhibited non-Fickian (anomalous) diffusion, Fickian diffusion and Super Case II transport release mechanisms. The ternary nanoconjugate hydrogels exhibited complete release (100%) within 48 h. The lowest concentration of DEAE-Dextran, Gellan - Ibuprofen - DEAE-Dextran (GIbDD) 2:0.125, increased the release of ibuprofen by 13.4% however higher concentrations of DEAE-Dextran decreased the release profile steadily. It was concluded that DEAE-Dextran has potentials in the formulation of modified (extended) release of ibuprofen. The most prominent mechanism of release of ibuprofen from the nanoconjugate hydrogel was Super Case II transport. SEM and AFM micrographs of the drug loaded composite pharmaceutical films exhibited concentric spheres with two and three layers for the binary and ternary films respectively. This supports the evidence of internalization of ibuprofen by the polyelectrolyte complex. The FTIR and DSC results confirmed electrostatic and hydrophobic interactions between ibuprofen and DEAE-Dextran as well as between gellan and DEAE-Dextran. Thermal analysis revealed that plain bilayer films were thermally more stable than composite films. The addition of ibuprofen significantly increased (p < 0.05, n = 4) the swelling ratio of the films compared with films without the drug. The drug loaded bilayer films exhibited Fickian diffusion mechanism while the dominating mechanism for composite films was anomalous (Non-Fickian) transport. From the foregoing, it was evident that ibuprofen-polymer nanoconjugate present a novel tool for the delivery of ibuprofen with potential application for transdermal delivery.
33
Baker, Nicola Louise. "Screening for new natural drugs and drug resistance determinants in African trypanosomiasis". Thesis, London School of Hygiene and Tropical Medicine (University of London), 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590629.
Texto completo da fonte
34
Stephen, Linda J. "Antiepileptic drugs - treating populations". Thesis, University of Glasgow, 2010. http://theses.gla.ac.uk/2005/.
Texto completo da fonteResumo:
Epilepsy affects 50 million people world-wide. Since 1982, the Western Infirmary Epilepsy Unit has provided a specialist service for over 6900 people with suspected and established seizure disorders. The twelve studies detailed in this thesis discuss the management of epilepsy in different patient populations, and explore beneficial and adverse effects of antiepileptic drugs (AEDs). AED development has allowed advances in pharmacological treatment of localisation-related epilepsies. Thus, outcomes were investigated in 550 such patients followed-up at the epilepsy clinic over 13 years (Paper i). Of these, 312 (57%) became seizure-free on medication. Those with hippocampal sclerosis had the poorest outcome (p<0.01), and a higher incidence of febrile convulsions (p<0.001). Although many patients benefited from AED therapy, results may be biased, given this cross-sectional study analysed data from both newly diagnosed patients, and those with drug-resistant seizures. Many people with epilepsy take more than one AED, although supportive evidence is sparse. Hence, polytherapy outcomes in 2881 patients registered with the Epilepsy Unit database were examined (Paper ii). Of these, 1617 (56%) were seizure-free, with 332 (21%) taking more than one AED (287 on two, 86%; 42 on three, 13%; 3 on four, 1%). There were 40 duotherapy and 28 triple therapy combinations resulting in seizure freedom. Therefore, combining two or three, but rarely four AEDs may be useful for patients not responding to monotherapy. Because this was a retrospective analysis of newly treated patients and those with refractory epilepsy, the analysis was subject to bias. Lack of a control group was also a weakness. Epilepsy Unit staff are therefore now examining similar outcomes in a large population of newly treated patients only. To establish the place of recently marketed AEDs in clinical practice, four studies examined prospectively the efficacy and tolerability of the novel agent, topiramate, in uncontrolled epilepsy. Adjunctive topiramate was administered in 170 patients with refractory seizures (Paper iii). Seizure frequency and adverse events were monitored. Patients were followed-up until seizure freedom for ≥ 6 months, ≥ 50% or <50% seizure reduction, intolerable side-effects, or lack of efficacy occurred. Seizure freedom was achieved in 39 (23%) patients. A ≥50% reduction in seizure frequency was reported in 80 (47%) others. Doses were often lower than those in regulatory studies. Efficacy as monotherapy was also demonstrated. Using the same end-points, topiramate was added to AED regimens of 64 patients with learning disabilities and epilepsy (Paper iv). Remission from seizures was established in 16 (25%). In similar fashion, levetiracetam was started in 156 patients with uncontrolled epilepsy (Paper v). Of these, 40 (26%) became seizure-free, many on low doses. When the drug was added to AED regimens in 64 patients with learning disabilities, 24 (38%) became seizure-free for at least 6 months (Paper vi). Caregiver quality-of-life scores improved significantly with levetiracetam (p<0.001). It is important to recognise that for all four audits results may be biased due to their observational nature, and the fact that they were undertaken at a single centre, with no control group. For patients with learning disabilities, small numbers, and retrospective baseline recordings for some could also have introduced bias. In Papers vii, viii and ix, findings from longitudinal studies in teenagers, people with learning disabilities and epilepsy, and newly diagnosed elderly patients attending the Epilepsy Unit, are reported. At the Teenager Clinic, 301 adolescents were reviewed over four years (Paper vii). Epilepsy was excluded in 135 (45%), five taking AEDs. A single seizure occurred in 22 others. In the 144 with epilepsy, seizure freedom for ≥ 12 months was attained in 76 (53%), but outcomes were poorer than expected. Neuroimaging was abnormal in 27 (43%). Newly diagnosed patients fared better than those taking treatment (p<0.05). More teenagers with primary generalised seizures (60%) attained remission, compared to those with focal-onset seizures (46%) (p<0.02). The retrospective natures of the analysis, and lack of control group may have biased results, thus making statistical conclusions inaccurate. Findings suggested the need for improved services. Over four years, 214 patients with learning disabilities and refractory epilepsy were followed-up (Paper viii). Although it is generally thought these individuals’ seizures are difficult to control, 59 (43%) became seizure-free for ≥ 12 months with AEDs. There was no change in quality-of-life scoring during this time, and no relationship between extent of learning disability and seizure control. The observational nature of the audit, and lack of control group may have biased results. Currently, there are few data on elderly people with epilepsy. Thus, outcomes over a 20-year period in 117 newly diagnosed senior citizens were examined (Paper ix). After starting AED treatment, 93 (79%) became seizure-free for ≥ 12 months, 73 (62%) with their first drug. Prognosis was better than in younger patients, and for those with fewer pre-treatment seizures (p=0.0078). Again bias may have been introduced because of the study’s observational nature and lack of control group. The final studies concentrate on AED-related adverse effects (Papers x, xi and xii). Bone changes have been reported with AED use. Hence, the relationship between bone mineral density, and long-term AED treatment in 78 older adults (47 post-menopausal women, 31 men), taking hepatic enzyme-inducing or non-inducing AEDs, was explored in a case-controlled study (Paper x). Men had significantly lower bone mineral density than controls at the lumbar spine (p<0.01), and neck of femur (p<0.005). Women had statistically reduced bone mineral density at the femoral neck (p<0.05). It was concluded that long-term AED treatment is an independent risk factor for reduced bone mineral density in people with epilepsy. As sodium valproate may be associated with metabolic changes and polycystic ovarian syndrome, hormone profiles were compared in 76 young men and women taking sodium valproate or lamotrigine monotherapy, to assess whether a pharmacological effect of valproate was responsible (Paper xi). Results revealed only four obese females exhibiting biochemical characteristics of polycystic ovarian syndrome (p=0.05), with obese patients of both sexes (p=0.01), and valproate-treated men (p=0.03) having higher insulin concentrations. Results are not significant when corrected for multiple comparisons. It can therefore be concluded that no differences in metabolic indices between patients taking sodium valproate or lamotrigine existed. To examine further effects on androgenic hormones, and the efficacy and tolerability of sodium valproate and lamotrigine monotherapy, a randomised, prospective study in 225 patients was performed (Paper xii). Patients were recruited if they presented with a minimum of two unprovoked seizures of any type, or a single seizure and underlying neuropathology. Of patients with partial-onset seizures, 81 received sodium valproate and 80 were randomised to receive lamotrigine. Of those with idiopathic generalised epilepsies, 30 received sodium valproate and 34 took lamotrigine. Seizure-free rates were identical in both arms at twelve months between the valproate and lamotrigine cohorts. There was a trend towards superiority for valproate (57% seizure-free) over lamotrigine (35% seizure-free) for patients with idiopathic generalised epilepsies (p=0.09), but a converse separation of outcomes for localisation-related epilepsies (43% seizure-free with valproate, 53% seizure-free with lamotrigine, p=0.24). More patients taking sodium valproate withdrew due to adverse events (p=0.046), eight because of weight gain.
35
Li, Jian. "Ciliotoxicity of intranasal drugs". Thesis, Queen's University Belfast, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317473.
Texto completo da fonte
36
Ridout, G. "Percutaneous absorption of drugs". Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373320.
Texto completo da fonte
37
Walker, Teneille. "Therapeutic Drugs in Cancer". VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1722.
Texto completo da fonteResumo:
The first study examined the interaction between low doses of the multi-kinase inhibitor sorafenib and the histone deacetylase inhibitor vorinostat in colon cancer cells. Sorafenib and vorinostat synergized to kill HCT116 and SW480 cells. In SW480 cells, sorafenib+vorinostat toxicity correlated with CD95 activation and CD95-stimulated autophagy. Drug lethality in SW480 cells was blocked by knock down of CD95. In SW620 cells that are patient matched to SW480 cells, sorafenib+vorinostat toxicity was significantly reduced that correlated with a lack of CD95 activation and lower expression of ceramide synthase 6 (LASS6). Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and tumor cell killing, whereas knock down of LASS6 in SW480 cells suppressed CD95 activation. In HCT116 cells, sorafenib+vorinostat did not increase CD95 plasma membrane levels, weakly induced caspase 8 association with CD95, and knock down of CD95 enhanced drug lethality. In HCT116 cells sorafenib+vorinostat treatment caused CD95-dependent autophagy that was a protective signal. Thus, treatment of tumor cells with sorafenib+vorinostat activates CD95 that promotes viability via autophagy or degrades survival via extrinsic or intrinsic pathways. Drug-induced activation of the de novo ceramide synthesis pathway plays a key role in CD95 activation. The second project explores the mechanism by which the combination of 17AAG, an hsp90 inhibitor, and PD184352, a MEK1/2 inhibitor alters survival in colon cancer cells. 17AAG and PD184352 synergized to kill HCT116 and SW480 cells. In HCT116 cells drug-exposure increased CD95 plasma membrane levels In SW620 cells, 17AAG and PD184352 toxicity was significantly reduced that correlated with a lack of CD95 activation and lower expression LASS6. Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and tumor cell killing. In Mia Paca2 cells, a pancreatic cell line, inhibition of caspase 8 or overexpression of c-FLIP-s suppressed cell killing by PD184352 and 17AAG exposure. Drug lethality in Mia Paca2 cells was blocked by knock down of CD95. Additionally, overexpression of Bcl-xL or knockdown of caspase 9 decreased cell killing in 17AAG and PD184352 combination treatment. Thus, 17AAG+PD184352 exposure activates the extrinsic and intrinsic apoptotic pathways to kill Mia Paca2 cells. This document was created in Microsoft Word 2000.
38
Crispim, Rute Irene Claudio. "Impact of the national drugs politics (NDP) in the access the gratuitous Drugs". Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1907.
Texto completo da fonteResumo:
nÃo hÃThis work aims at the investigation of access to medicines free for users of SUS through the National Drug Policy. The database was used to PENAD98/03. In this research used is a model that conceitua access according to the individual use of the public health service, and receiving the medicine free taking into account the characteristics that lead to use those services. Through Logist model by the method of maximum likelihood has been unable to verify that access to free medicines rose between 6% and 9 percentage points five years after the promulgation of the PNM. The descriptive review with respect to the receipt of free product per lane-income, shows that even among users of SUS, those with higher incomes have a lower probability of receiving free medication. And for the carriers of chronic diseases such as diabetes and hypertension, are more likely to receive free medicine. These results show some effectiveness of the public service to reach those who are really in need.
Este trabalho tem como objetivo a investigaÃÃo do acesso aos medicamentos gratuitos para usuÃrios do SUS por meio da PolÃtica Nacional de Medicamentos. A base de dados utilizada foi a PENAD98/03. Nesta pesquisa utilizou-se o modelo que conceitua acesso de acordo com a utilizaÃÃo do individuo ao serviÃo pÃblico de saÃde, e recebimento do medicamento gratuito levando em conta as caracterÃsticas que levam a utilizar esses serviÃos. Mediante modelo Logist atravÃs do mÃtodo de mÃxima verossimilhanÃa foi possÃvel verificar que o acesso a medicamentos gratuitos aumentou entre 6 e 9% pontos percentuais cinco anos apÃs a promulgaÃÃo da PNM. A analise descritiva com relaÃÃo ao recebimento de medicamento gratuito por faixa de renda, mostra que mesmo entre os usuÃrios do SUS, aqueles com maiores rendimentos tÃm uma probabilidade menor de receber medicamentos gratuitos. E para os portadores de doenÃas crÃnicas como diabetes e hipertensÃo estes, tÃm maiores chances de receberem medicamentos gratuitos. Estes resultados demonstram certa eficÃcia do serviÃo pÃblico de atingir aqueles que realmente sÃo mais necessitados.
39
Li, Zezheng. "Estimating Minimum Effective Dose in Dose Response Studies". Fogler Library, University of Maine, 2009. http://www.library.umaine.edu/theses/pdf/LiZ2009.pdf.
Texto completo da fonte
40
Mahaguna, Vorapann. "Investigation of cellulose ether polymers in controlled drug delivery". Access restricted to users with UT Austin EID Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3037524.
Texto completo da fonte
41
Cook, Andrew T. "The effect of accelerated aging on peelable medical products seals /". Online version of thesis, 1994. http://hdl.handle.net/1850/11980.
Texto completo da fonte
42
Chittchang, Montakarn Johnston Thomas P. "Effect of secondary structure on paracellular transport of polypeptides". Diss., UMK access, 2004.
Encontre o texto completo da fonteResumo:
Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004."A dissertation in pharmaceutical sciences and chemistry." Advisor: Thomas P. Johnston. Typescript. Vita. Description based on contents viewed Feb. 23, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 202-223). Online version of the print edition.
43
McAndrew, Duncan Ross. "The structure of criminal networks". Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366272.
Texto completo da fonte
44
Mifsud, Janet. "Chiral aspects of the disposition and pharmacology of the enantiometers of ethosuximide". Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336672.
Texto completo da fonte
45
Triplett, Michael David. "Enabling solid lipid nanoparticle drug delivery technology by investigating improved production techniques". Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1101830018.
Texto completo da fonteResumo:
Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xv, 172 p.; also includes graphics (some col.). Includes bibliographical references (p. 161-172).
46
Gustafsson, Jörgen. "Synthesis of cyclohexenedicarbaldehydes and studies of their biologic activity". Lund : Organic Chemistry 2, Lund Institute of Technology, University of Lund, 1994. http://books.google.com/books?id=ULpqAAAAMAAJ.
Texto completo da fonte
47
Zhang, Feng. "Hot-melt extrusion as a novel technology to prepare sustained-release dosage forms /". Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
Texto completo da fonte
48
Foley, David William. "Substrate studies on PepT1". Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627919.
Texto completo da fonte
49
Hughes, Caitlin Elizabeth. "Overcoming obstacles to reform : making and shaping drug policy in contemporary Portugal and Australia /". Connect to thesis, 2006. http://eprints.unimelb.edu.au/archive/00003215.
Texto completo da fonte
50
Jonge, Jan-Willem de. "Diuretic drug cessation in general practice withdrawing diuretic drugs prescribed for ankle oedema /". [Maastricht : Maastricht : Rijksuniversiteit Limburg] ; University Library, Maastricht University [Host], 1993. http://arno.unimaas.nl/show.cgi?fid=6675.
Texto completo da fonte