Thesis (Ph. D.)--University of Wisconsin--Madison, 1952. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--New York University, 2001. / Includes bibliographical references (leaves 337-380).

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / Many pediatric patients require medications that are not available in age appropriate formulations, especially those with cardiovascular diseases. Furosemide and Captopril generally are produced in solid dosage forms for adults, and need to be fractionated and transformed in suspensions for use in children. The use of a suitable vehicle is critical to the preparation of a homogeneous, stable and palatable extemporaneous formulation that can guarantee the expected effect. In this work was evaluated the acceptability of a vehicle, named Gute, developed by a research group from Universidade Federal do CearÃ, considering that palatability is essential to treatment adherence in children. We analyzed the vehicle in different flavors with respect to the ability to mask the bitter taste of Captopril and Furosemide, the acceptance and preference without actives by healthy children and their parents, and the acceptance of extemporaneous formulations of the mentioned drugs administered to pediatric patients as prescribed. In the laboratory, eight panelists evaluated the masking ability of the vehicle flavored in mint, cherry, strawberry and neutral using a linear scale. ANOVA scores for bitterness intensity for captopril and furosemide showed that the flavored samples had significantly greater capacity of masking the bitter taste than the vehicle without flavor (neutral), however, there was no different between the flavors. 62 children 4-12 years and 21 guardians participated in the evaluation of the vehicle without actives flavored in mint, strawberry and cherry, using a facial-verbal hedonic scale with seven degrees. The three flavors were accepted and equally preferred by children and guardians. In hospitalized patients who received suspensions of Captopril (34) and furosemide (36), the flavors mint, strawberry and neutral acceptance was evaluated through the guardians with the hedonic scale and compared with the observation of the researcher .Suspensions in neutral and strawberry flavors were considered acceptable for both drugs. The correlation between the results from the two methods was moderate for Captopril, and absent Furosemide. The results for the neutral flavor showed that the addition of flavoring agents did not influenced in the acceptance and can be avoided in this case, an advantage in terms of safety for infants and neonates. / Muitos medicamentos necessÃrios a pacientes pediÃtricos nÃo sÃo disponÃveis em formulaÃÃes apropriadas à idade, principalmente aqueles que tratam doenÃas cardiovasculares. Captopril e Furosemida, de modo geral, sÃo produzidos na forma sÃlida em doses para adultos, e necessitam ser fracionados e transformados em suspensÃes para uso em crianÃas. O uso de um veÃculo adequado à crÃtico para o preparo de formulaÃÃes extemporÃneas homogÃneas, palatÃveis e estÃveis, que possam garantir o efeito esperado. Neste trabalho foi avaliada a aceitabilidade de um veÃculo com nome fantasia Gute, desenvolvido por um grupo de pesquisa da Universidade Federal do CearÃ, tendo em vista que a palatabilidade à essencial para a adesÃo ao tratamento em crianÃas. Analisou-se o veÃculo em diferentes sabores em relaÃÃo à capacidade de mascarar o gosto amargo de Captopril e Furosemida, sua aceitaÃÃo e preferÃncia sem ativos por crianÃas sadias e seus responsÃveis, bem como a aceitaÃÃo de formulaÃÃes extemporÃneas dos medicamentos citados, administradas a pacientes pediÃtricos, conforme prescriÃÃo. Em laboratÃrio, oito provadores avaliaram a capacidade de mascaramento do veÃculo flavorizado nos sabores menta, cereja, morango e neutro, utilizando uma escala linear. A anova dos valores de intensidade do sabor amargo, para Captopril e Furosemida, mostrou que a capacidade dos sabores flavorizados de mascarar o sabor amargo foi significativamente maior do que a do veÃculo sem sabor, contudo, os sabores nÃo diferiram entre si. Participaram da avaliaÃÃo do veÃculo sem ativos, nos sabores menta, morango e cereja, 62 crianÃas de 4 a 12 anos e 21 responsÃveis, usando uma escala hedÃnica facial-verbal de sete graus. Os trÃs sabores foram aceitos e igualmente preferidos pelas crianÃas e pelos responsÃveis. Com os pacientes internados que receberam suspensÃes de Captopril (34) e Furosemida (36), nos sabores menta, neutro e morango, a aceitaÃÃo foi avaliada atravÃs dos responsÃveis com uso da escala hedÃnica e comparada com a observaÃÃo da pesquisadora. As suspensÃes nos sabores neutro e morango foram consideradas aceitas para ambos os medicamentos. A correlaÃÃo entre os resultados provenientes dos dois mÃtodos de avaliaÃÃo da aceitaÃÃo foi moderada para Captopril, e para Furosemida, nÃo houve correlaÃÃo. Os resultados relativos ao sabor neutro mostraram que a adiÃÃo de flavorizantes nÃo influenciou na aceitaÃÃo das suspensÃes, podendo ser evitada nesses casos, uma vantagem em termos de seguranÃa para bebÃs e neonatos.

Organisations are continuously seeking for strategies to improve operations and gain competitive advantage. Maintenance tends to be a key management issue for many industrial companies. Maintenance management, being an integral part of manufacturing, can influence competitive companys‟ priorities, such as cost, quality and flexibility, and, hence, business strategy directly. The pharmaceutical industry also faces some unique challenges such as increasingly stringent safety and quality regulations, the effect of innovations in medical science and healthcare and a complex and costly design-to-market process (from product concept and development to market delivery). The industry is also going through turbulent times as it has to cope with challenges common to many other industries, how to deal with increasing competition, hold down costs, and expand. Regulatory compliance is one of the significant industry drivers for pharmaceutical companies. Regulations are enacted by government authorities to ensure public health and safety. The focus of regulation is on quality assurance and control in all areas such as receiving, manufacturing, storing, packaging, despatching and delivering. Apart from the required quality and safety checks, the regulations also mandate extensive record keeping of procedures, processes and systems. This treatise will investigate the maintenance management system of a pharmaceutical company and compare it to best practices. The true name of the pharmaceutical company that will be researched will not be disclosed for confidentiality reasons, instead it will be called My Pharmaceuticals. The company is based in Port Elizabeth. The research consists of a preliminary study to identify the problem areas in the maintenance management system within the company. A literature review of best practices in maintenance management systems combined with an investigation into the best pharmaceutical practices in maintenance management systems and regulatory controls are investigated and a model will be proposed to improve the current situation at the company.

Transthyretin (TTR) amyloidosis is a progressive, fatal disease in which deposition of amyloid derived from either mutant or wild-type TTR causes severe organ damage and dysfunction. TTR cardiomyopathy is an infiltrative, restrictive cardiomyopathy characterized by progressive left and right heart failure. Familial amyloid cardiomyopathy (FAC) is driven by pathogenic point mutations in the TTR gene that destabilize the TTR tetramer, prompting its dissociation into dimers and monomers, with subsequent misfolding, aggregation and deposition of toxic TTR amyloid aggregates in the myocardium. The most prevalent mutation that causes FAC is the V122I variant, carried by 3.4% of African Americans, that increases the risk of cardiomyopathic events several-fold in this population. AG10, a potent TTR kinetic stabilizer, prevents dissociation of V122I-TTR in serum samples obtained from patients with FAC. Further, we have described structural, biochemical, and animal studies of AG10 which reveal mechanistic and structural insights on the ability of AG10 to mimic the disease suppressing T119M variant in stabilizing TTR. The second part of the thesis discusses harnessing TTR as a platform to enhance in vivo half-life (t1/2) of therapeutic peptides. Native peptides typically display short in vivo t1/2, however conjugation of peptides to macromolecules causes steric hindrance which often harms the binding of peptides to target receptors, compromising the in vivo efficacy. Utilizing Gonadotropin Releasing Hormone (GnRH) as a model peptide, we show that t1/2 may be extended without compromising potency. Our approach involves endowing peptides with a small molecule that binds reversibly to the serum protein transthyretin. Our strategy was effective in enhancing the t1/2 of an agonist for GnRH receptor while maintaining its binding affinity, which was translated into superior in vivo efficacy. The third and final part of the thesis describes our effort on developing a fluorescent probe to quantify TTR in human serum using fluorescence polarization. TTR is used as a marker for nutritional and inflammatory status in critical patients. This assay development has the potential to minimize lab cost, effort, and time with regards to determination of TTR concentration in patients.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements of the degree of Master of Science in Medicine in Pharmaceutical Affairs. / Many will be disappointed to learn that pharmacoeconomic evaluations provide information, not answers. Although pharmacoeconomics broadens the perspective taken in evaluating drug therapies, the final drug therapy decision is still influenced by clinician preferences, patient desires, and the working and politics of the healthcare delivery system”. 1 Globally and in South Africa there is an increasing pressure on healthcare resources. These pressures have exponents both in the supply and demand arms of the economic equation and have set the scene for the development of a new discipline in healthcare. Pharmacoeconomics can be defined as “the description and analysis of the cost of drug therapy of health care systems and society”. 2 Pharmacoeconomics assesses the ratio of the cost to the consequences of specific drug therapies using a technique called Cost Effective analysis which uses tools such as Cost Minimisation analysis, Cost Effective analysis and Cost Benefit analysis / IT2018

No description available.

Background: Primary cilia are cellular organelles project from the cell surface of mammalian cell and play important roles in vertebrate development, organogenesis, health, and others genetic diseases. Primary cilium functions as a mechano-sensor and chemo-sensor. Defect in primary cilia causes the progression of polycystic kidney disease (PKD) which further leads to the inflammatory responses. We, therefore, investigated the role of Toll-like receptors 4 and 9 (TLR) in primary cilia towards PKD. Purpose: The main purpose of the proposed study is to identify and target the immune reactive proteins i.e. TLRs in the primary cilia. By targeting those primary cilia immune reactive proteins using suitable agonist and antagonists to study the control of cystic formation and their progression mechanisms. Methods: To target the ciliary immune TLR proteins (TLR4 and TLR9), we did immunostaining to evaluate their localization on primary cilia. Cilia lengths were measured and compared using differential interference contrast (DIC) and fluorescent imaging techniques. The in vitro3D cyst progression was monitored by adding agonists lipopolysaccharide (LPS) and oligodeoxynucleotides (ODN) and antagonist 4-hydroxy chloroquine (HCQ). Results: From our results we found that the TLR antagonist HCQ increases ciliary length in treated scrambled control, Pkd2knockout (KO) and TLR4KOcells as an immune response, whereas opposite results were observed with TLR9KO. However, the selected agonists for TLRs (LPS/ODN) increases cilia length in TLR9KO cells and decreases scrambled control, Pkd2KO and TLR4KO. In our 3D cyst cultures, we used agonists and antagonist for both the TLRs and observed that the cyst formations and progressions were inversely related to the cilia lengths. From these observations, we speculated that the new ciliary TLR proteins have a role in cystic progression. In conclusion, we found that the TLRs agonists/antagonist can modulate cilia length and TLRs role in inflammatory actions. The primary cilium already has central roles throughout cell biology, but here we propose, for the first time, that the cilium and the regulation of its structural importance in inflammation of PKD.

No description available.

Thesis (LL. M.)--University of Toronto, 2004. / Adviser: Colleen Flood.