published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

Thesis (Ph. D.)--University of Minnesota, 1932. / Caption title. Thesis note on p. [1] of each part. Vita on p. [1] on cover. Parts 2-3 have title: Action of cathartics on isolated dog's colon. Reprinted from the Archives of surgery, v. 27, 1933. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references. Bibliography on cover.

Thesis (Ph. D.)--University of Minnesota, 1932. / Caption title. Thesis note on p. [1] of each part. Vita on p. [1] on cover. Parts 2-3 have title: Action of cathartics on isolated dog's colon. Reprinted from the Archives of surgery, v. 27, 1933. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references. Bibliography on cover.

Whole fruits, grains and vegetables contain thousands of potential disease-fighting, healthpromoting nutrients. These foods play a critical role in bowel function, especially in the elderly. Strong epidemiological evidence has shown that greater amounts of crude dietary fibre are associated with a lesser prevalence of constipation and other gastrointestinal disorders. Constipation usually presents as a variety of symptoms, including reduced frequency of defaecation and impacted forms of stools and/or increased effort required to defaecate. Constipation is a problem that could affect any person at any time in his or her life, but in the elderly is more prevalent.Although anecdotal reports and dietary advice have suggested the use of kiwifruit as a laxative in humans, there are, at present no data available to support this. Kiwifruit is reported as the most nutrient-rich of the top 27 fruits eaten in the world today. The laxative property of kiwifruit could provide a natural remedy for constipation and would be cheaper than the laxatives on the market.Objective: The main objective of this study was to investigate if kiwifruit can act as a laxative, especially in elderly people.Study Design and Methods: This study was carried out in two stages, as a pilot and then a main study. In the pilot study, 71 participants (aged 18 - 50y) were divided into Group I and Group II. Group I made no changes to their normal diet for a six weeks period, while Group II were asked to add one kiwifruit for every 30kg body weight per day to their diet for a six week period. After the six weeks, the two experimental groups crossed over, maintaining the dietary regime followed by the other group for a further six weeks. So each subject was his or her own control. Daily recording of the frequency and characteristics of the stool were made by the participants in a diary. In the main study, 42 participants (aged 60 years and over) carried out the same dietary regime as the pilot study subjects. Elderly subjects of Group I made no changes to their diet, but was asked to record their daily frequency and characteristics of their stool for 3weeks. Group II subjects ate one kiwifruit for every 30kg body weight per day for a period of 3weeks. After the three weeks period, the two groups crossed over.Results: It was found from the pilot study that kiwifruit consumption was associated with significant softening of the stool (P<0.001); a significant increase in bulking of the stool (P=0.034) and the ease of bowel movement was improved (P<0.001). For the main study, kiwifruit consumption also showed softening of the stool (P<0.001) and the ease of bowel movement was improved (P<0.001), there was a slight but significant increase in bowel frequency (P=0.012) and the bulking of stool (P=0.002).Conclusion: The results from this study provide evidence that consumption of kiwifruit enhances laxation and that bowel function can be improved through changes in diet, both for younger and elderly people.

Thesis (MAppSc--Applied Science)--Auckland University of Technology, 2003. / Also held in print (100 leaves, 30 cm.) in Wellesley Theses Collection. (T 613.28 PAT).

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A Operculina alata, conhecida como jalapa, à uma planta cuja raiz à utilizada pela populaÃÃo em virtude do seu efeito laxante. Um ensaio clÃnico duplo cego, controlado por placebo, randomizado e paralelo avaliou a eficÃcia terapÃutica da tintura de jalapa no tratamento da constipaÃÃo intestinal funcional, na Unidade de Farmacologia ClÃnica, CearÃ, Brasil. Foram dois grupos de tratamento, o grupo Jalapa e o grupo Placebo, ambos compostos por 38 voluntÃrios com constipaÃÃo intestinal funcional. O estudo teve 3 fases, cada uma com duraÃÃo de 7 dias, em que o voluntÃrio registrava num diÃrio dados das evacuaÃÃes. No prÃ-tratamento houve a seleÃÃo de voluntÃrios. No tratamento ocorreu a randomizaÃÃo e administraÃÃo da tintura de jalapa ou placebo. No pÃs-tratamento os voluntÃrios foram observados apÃs suspensÃo da tintura de jalapa ou placebo. A eficÃcia foi avaliada atravÃs das variÃveis primÃrias: frequÃncia mÃdia de evacuaÃÃes (FME), consistÃncia mÃdia das fezes (CMF) e melhora global da constipaÃÃo (MGC). As variÃveis secundÃrias foram proporÃÃo de evacuaÃÃes com dor (PED), proporÃÃo de evacuaÃÃes com esforÃo (PEE), nÃmero de dias seguidos sem evacuar (DSE) e grau de melhora da constipaÃÃo. Todos os voluntÃrios participantes foram do sexo feminino. No grupo Placebo houve perda de segmento de 5 voluntÃrias e no grupo Jalapa, apenas duas desistiram. A maioria das voluntÃrias procedia da cidade de Fortaleza. O menor grau de escolaridade encontrado foi o ensino fundamental incompleto representado por 10,5% da amostra. Havia uso de agentes laxativos por 69,8% das voluntÃrias. No prÃ-tratamento, os grupos Jalapa e Placebo mostraram semelhanÃa estatÃstica quanto à idade, IMC e CMF, mas diferiram quanto a FME, onde o grupo Placebo (0321  0,108) apresentou valores maiores que os grupo Jalapa (0,262  0,132). No tratamento e pÃs-tratamento, a FME e a CMF foram significantemente maiores no grupo Jalapa que no grupo Placebo, com 55,26% dos voluntÃrios do grupo Jalapa apresentando aumento simultÃneo dos valores da FME e CMF, o que foi representado pela MGC, com probabilidade 3,5 vezes maior de melhorar da constipaÃÃo com a tintura de jalapa que com o placebo. Os valores da PED, da PEE e do DSE no grupo Jalapa foram menores e estatisticamente significantes que os do grupo Placebo nas fases de tratamento e pÃs-tratamento. A proporÃÃo de voluntÃrios do grupo Jalapa que relataram alÃvio razoÃvel e total dos sintomas da constipaÃÃo nas fases de tratamento e pÃs-tratamento foram significantemente maiores que no grupo Placebo. Houve alteraÃÃes da pressÃo arterial sistÃlica, diastÃlica e frequÃncia cardÃaca, mas foram consideradas sem relevÃncia clÃnica. NÃo ocorreram alteraÃÃes de massa corporal e eventos adversos graves, mas destacaram-se a tontura, cefalÃia e dor abdominal. Este estudo concluiu que a tintura de jalapa à eficaz no tratamento agudo da constipaÃÃo intestinal funcional nos voluntÃrios estudados. / The Operculina alata, known as Jalapa, is a plant whose root is used by the population because of its laxative effect. A double-blind clinical trial, placebo controlled, randomized, parallel evaluated the therapeutic efficacy of tincture of Jalapa in the treatment of functional constipation in the Unit of Clinical Pharmacology, CearÃ, Brazil. There were two treatment groups, the Jalapa group and the Placebo group, both consisting of 38 volunteers with functional constipation. The study had 3 phases, seven days in each phase, in which the volunteer data recorded in a diary of bowel movements. During the pre-treatment there was the selection of volunteers. In the treatment occurred the randomization and administration of tincture of Jalapa or placebo. The post-treatment were observed after the voluntary suspension of tincture of Jalapa or placebo. The effectiveness was evaluated through the primary variables: average frequency of evacuations (AFE), average consistency of faeces (ACF) and global improvement of constipation (GIC). Secondary variables were the proportion of evacuations with pain (PED), proportion of effort evacuations (PEE), number of consecutive days without evacuation (DWE) and degree of improvement in constipation. All volunteer participants were female. In the placebo group there was lost segment of 5 volunteers and in the Jalapa group, only two were removed. Most volunteers came from the city of Fortaleza. The lower level of education found the primary school was represented by 10.5% of the sample. There was use of laxative agents by 69.8% of volunteers. In the pre-treatment, Jalapa and Placebo groups showed statistically similar in age, BMI and ACF, but differed in the AFE, where the Placebo group (0321  0108) showed that the largest group Jalapa (0262  0132). In the treatment and post-treatment, the AFE and ACF were significantly higher in Jalapa group than in the Placebo group, with 55.26% of volunteers of the Jalapa group showing increased values of AFE and ACF, which was represented by the GIC with 3.5 times more likely to improve the constipation with the tincture of Jalapa that with placebo. The values of the PED, the PEE and the DWE in Jalapa group were lower and statistically significant than those in the placebo group during treatment and post-treatment. The proportion of volunteers reported that the Jalapa group reasonable and complete relief of symptoms of constipation during treatment and after treatment was significantly higher than in the placebo group. There were changes in systolic blood pressure, diastolic and heart rate, but were without clinical relevance. There were no changes in body mass and serious adverse events, but highlighted to dizziness, headache and abdominal pain. This study found that the tincture of Jalapa is effective in the acute treatment of functional constipation in volunteers studied.

Benefibra is a food supplement, produced by company Novartis s.r.o., which was launched onto the pharmaceutical market 3 years ago. Althought so many Print campaigns, TV campaigns and other marketing activities have been organised, Benefibra's launch wasn't a great success. The main goal of my thesis is the analysis of Benefibra marketing mix, to find reasons of the unsuccesfull launch onto the Czech market and to suggest changes in marketing mix, that would lead to reach goals, which company Novartis has determined during launching of Benefibra on the czech market in September 2006.

nÃo hà / ConstipaÃÃo à um problema clÃnico comum que compreende uma constelaÃÃo de sintomas como excessivo esforÃo, fezes duras, sensaÃÃo de evacuaÃÃo incompleta, uso de manobras digitais, ou defecaÃÃo infreqÃente. Seu tratamento emprega medicamentos que aumentem a freqÃÃncia e facilitem as evacuaÃÃes, bem como mudanÃas nos hÃbitos de vida. O objetivo desse estudo foi avaliar seguranÃa, eficÃcia terapÃutica e validar um mÃtodo analÃtico para a gelÃia TamarineÂ, um fitoterÃpico largamente utilizado como laxante, em pacientes com constipaÃÃo intestinal funcional. Foi realizado o perfil cromatogrÃfico da gelÃia Tamarine para confirmaÃÃo dos seus constituintes e anÃlise de estabilidade empregando cromatografia lÃquida de alta eficiÃncia (CLAE), onde seus principais constituintes foram identificados atravÃs dos tempos de retenÃÃo caracterÃsticos. A anÃlise de estabilidade da formulaÃÃo foi executada comparando os cromatogramas de lotes recÃm-fabricados com lotes apÃs 2 anos de fabricaÃÃo. O mÃtodo desenvolvido comprovou a qualidade das amostras testadas e sua estabilidade apÃs 2 anos de armazenamento. O estudo de toxicologia clÃnica foi do tipo aberto, realizado em 24 voluntÃrios saudÃveis de ambos os sexos que receberam diariamente a administraÃÃo de 5g da gelÃia Tamarine por 28 dias consecutivos. Os voluntÃrios foram avaliados antes, durante e ao final do perÃodo de administraÃÃo atravÃs de histÃria mÃdica, exame fÃsicos e laboratoriais. A formulaÃÃo foi bem tolerada e foram observados feitos adversos como cÃlicas (83,3%), aumento de evacuaÃÃes (58,3%), diarrÃia (20,8%), flatulÃncia e nÃuseas (12,5%). Os parÃmetros hematolÃgicos, metabÃlicos, funÃÃo renal e hepÃtica sofreram variaÃÃes pontuais ao longo do estudo, entretanto, consideradas sem significado clÃnico. O estudo de eficÃcia terapÃutica foi do tipo controlado, paralelo, aberto e randomizado empregando 124 voluntÃrios com constipaÃÃo intestinal funcional, selecionados de acordo com os critÃrios de Roma II e distribuÃdos aleatoriamente entre os grupos de tratamento com a gelÃia Tamarine (TAM) ou Metamucil (MET). Os pacientes em tratamento eram avaliados quinzenalmente para levantamento de efeitos adversos e avaliaÃÃo da eficÃcia feita pelo registro das evacuaÃÃes diÃrias, consistÃncia das fezes e pela melhora global referida pelos mesmos. A maioria dos pacientes apresentou dieta pobre em fibras e baixa ingestÃo de lÃquidos, entretanto, suas dietas nÃo foram alteradas durante o tratamento, as orientaÃÃes nutricionais foram realizadas ao final do estudo para nÃo interferir nos resultados. O uso do TAM aumentou o nÃmero de evacuaÃÃes nos pacientes apÃs 14 e 28 dias de tratamento, quando comparado com o perÃodo inicial de seleÃÃo. No 7o, 14 o, 21 o e 28 o dias a resposta dos pacientes que faziam seu uso foi maior do que o grupo tratado com MET (p&#61500;0,001), bem como a taxa de melhora 166,7% (p=0,003). A consistÃncia das fezes tambÃm melhorou, tornando-se mais amolecidas nos dois grupos. Tratamento com TAM reduziu a consistÃncia das fezes em todo o perÃodo de tratamento (p<0,001) enquanto que o controle teve reduÃÃo apenas na terceira semana (p<0,05). A avaliaÃÃo global dos pacientes (p=0,01 e 0,0367) e do investigador (p=0,0083 e 0,0193) realizadas no 14 e 28 dias de tratamento mostrou melhor aceitaÃÃo para o grupo tratado com TAM nos dois perÃodos de avaliaÃÃo. Nenhum sinal de toxicidade clÃnica ou laboratorial foi observado em todo o perÃodo de tratamento. O presente ensaio clÃnico conclui que a administraÃÃo de 5g da gelÃia Tamarine à segura e eficaz no tratamento da constipaÃÃo intestinal. / Constipation is a common clinical problem that comprises a constellation of symptoms that include excessive straining, hard stools, feeling of incomplete evacuation, use of digital maneuvers, or infrequent defecation. The treatment is composed by behavioral measures and a therapeutic approach. Initial intervention should include dietary measures and fiber supplements; however, if fiber supplement action is ineffective, substances that increase the fecal bolus, lubricants, osmotic agents and laxatives can be used. The aim of the present study was to establish the efficacy, safety and validate an analytical method. Tamarine jelly, a phytotherapic product from Barrenne IndÃstria FarmacÃutica Ltda. a phytomedicine used as laxative. The research project with the experimental protocol and informed consent, were submitted to and approved by the Research Ethics Committee of UFC. The chromatographic profiles of Tamarine jelly was done for confirmation of their constituents and stability analysis using high performance liquid chromatography (HPLC). The method showed the quality of the samples tested and its stability after 2 years of storage. The toxicology clinical trial consisted of an open study with 24 healthy volunteers of both sexes, with a mean age of 26.8 &#61617;&#61472;7.8 years, who orally received a daily dose of 5g Tamarine for 28 uninterrupted days. The volunteers were included in the study only when considered healthy after clinical evaluation, physical examination and laboratory tests which preceded the study. The laboratory tests included: heamatologic, biochemical and serologic analysis. This evaluation was repeated after the first, second, third and fourth week of treatment and at post-study. The jelly was well tolerated, however, some adverse gastrointestinal events were observed. Twenty volunteers (83.3%) reported episodes of light intestinal colic followed by hyperdefecation, five (20.8%) reported diarrhea and three (12.5%) flatulence and nausea. The clinical, electrocardiographic and laboratory tests did not show evidence of toxicity in the various organs and systems evaluated. The efficacy was evaluated in 124 constipated patients selected by Rome II criteria. The investigation was designed as a controlled, parallel and opened. After the selection period, Tamarine (TAM) or Metamucil (MET) was administered. Patients were provided with diary sheets to record each bowel movement and associated subjective symptoms rating stool consistency, abdominal pain and flatus. The efficacy and safety analyzed after each 14 days of treatment by the information recorded on diary and a global assessment of efficacy. Volunteers continuing with their routine activities and maintaining their normal general diets even showing a low consumption of fiber and liquids. The nutritional guidelines were implemented at the end of the study not to interfere in the results. TAM increased bowel frequency after 14 and 28 days when compared with no treatment period and on 7o, 14 o, 21o and 28o days was higher the MET (p<0,001). The stool consistency was changed and became softer in both groups. The alterations improved by TAM was observed in all treatment period (p<0,001) and MET changed only on the third week (p<0,05) . The patientâs global efficacy score (p=0,01 e 0,0367) and investigatorâs (p=0,0083 e 0,0193) realized that on 14 and 28 days of treatment was superior for the TAM group compared with MET. No signs of clinical or laboratory toxicity was observed throughout the treatment period. Confirming their traditional use, the administration of 5g of jelly Tamarine  phytotherapic proved to be safe and effective in the treatment of constipation.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The use of herbal medicines as an alternative treatment has increased by the belief that natural products do not cause damage to health. However cases in which natural products are added of synthetic drugs not declared, presumably to enhance the effectiveness them have been reported in the literature. In the case of weight loss formulations the main adulterants found are appetite suppressants, antidepressants, benzodiazepines, diuretics and laxatives. The identification of these frauds is only possible by applying the analytical methods able to detect the presence of adulterants in the formulations. This paper describes the development of two methods employing separation techniques with electrochemical detection for the determination of diuretics and laxatives as adulterants in herbal products. The method employing capillary zone electrophoresis (CZE) with contactless conductivity detection (C4D) allows the simultaneous determination of amiloride, chlorthalidone, hydrochlorothiazide, furosemide and phenolphthalein in the following optimized conditions: working electrolyte phosphate buffer 20 mmol L-1 (pH 9.2) containing 30% methanol (v/v) separation potential -15 kV, temperature 25 °C, injection hydrodynamic by gravity in 20 cm for 60 seconds. The method employing ion pair chromatography (IPC) with pulsed amperometric detection (PAD) allows the determination of hydrochlorothiazide, chlorthalidone and furosemide on the following conditions: mobile phase phosphate buffer 5 mmol L-1 (pH 4.5) containing SDS 0.3 mmol L-1 and 50% methanol (v/v), sample potential of +0.8 V, the cleaning potential of -0.2 V and +1.0 V, and flow rate of 1.0 mL/min. Both methods were validated in the parameters of linearity, limit of detection limit of quantification, precision, accuracy and selectivity, and were applied in the analysis of 26 samples of natural weight loss products purchased from pharmacies in nine Brazilian states. In three of 26 samples were identified the presence of illegal diuretic hydrochlorothiazide in concentrations ranging from 0.6 to 7.0 mg/capsule. In addition, five other samples called naturals contained declared on the label of the packaging the presence of synthetic diuretics hydrochlorothiazide or furosemide. Both methods were able to identify the adulterants present in samples with high selectivity and sensitivity. Furthermore, they presented very approximate results in the concentration of adulterants found in the formulations. There is still no unified regulation established by the government for control of herbal products. Each country has its laws, but the marketing is global. Maybe this is the reason why the adulteration of natural products has been a recurring practice in various parts of the world. Therefore, effective regulation for the natural products can result in the reduction of these offenses, and punishment of offenders, thus ensuring the rights of consumers to make quality treatment, safe and effective, without prejudice to health. Keywords: Pharmaceutical formulations, adulterants, diuretics, laxatives, methods of separation, electrochemical detection. / O uso de ervas medicinais como tratamento alternativo tem crescido por se acreditar que produtos naturais não causam danos à saúde. No entanto casos de adulteração de produtos naturais com adição não declarada de fármacos sintéticos, presumidamente para aumentar a eficácia dos mesmos, têm sido relatados na literatura. No caso de formulações emagrecedoras os principais adulterantes já encontrados são anorexígenos, antidepressivos, benzodiazepínicos, diuréticos e laxantes. A identificação destas fraudes só é possível com a aplicação de metodologias analíticas capazes de detectar a presença destes adulterantes nas formulações. Este trabalho descreve o desenvolvimento de duas metodologias empregando técnicas de separação com detecção eletroquímica para a determinação de diuréticos e laxantes como adulterantes em produtos naturais. O método empregando eletroforese capilar de zona (CZE) com detecção por condutividade sem contato (C4D) permite a determinação simultânea de amilorida, clortalidona, hidroclorotiazida, furosemida e fenolftaleína nas condições otimizadas: eletrólito de trabalho tampão fosfato 20 mmol L-1 (pH 9,2) contendo metanol 30% (v/v), potencial de separação -15 Kv, temperatura 25 °C; injeção hidrodinâmica por gravidade em 20 cm durante 60 s. O método empregando cromatografia de par iônico (IPC) com detecção por amperometria pulsada (PAD) permite a determinação de hidroclorotiazida, clortalidona e furosemida nas seguintes condições: fase móvel tampão fosfato 5 mmol L-1 (pH 4,5) contendo SDS 0,3 mmol L-1 e metanol 50% (v/v); potencial de amostragem de +0,8 V; potenciais de limpeza de -0,2 V e +1,0 V; e fluxo de 1,0 mL/min. Os dois métodos foram validados nos parâmetros de linearidade, limite de detecção, limite de quantificação, precisão, exatidão e seletividade e, foram aplicados na análise de 26 amostras de produtos naturais emagrecedores adquiridos de farmácias de manipulação de nove estados brasileiros. Em três das 26 amostras foi identificada a presença ilegal do diurético hidroclorotiazida em concentrações que variaram de 0,6 a 7,0 mg/cápsula. Além disso, outras cinco amostras ditas naturais continham declarado no rótulo das embalagens a presença dos diuréticos sintéticos hidroclorotiazida ou furosemida. Os dois métodos foram capazes de identificar os adulterantes presentes nas amostras com alta seletividade e sensibilidade. Além disso, apresentaram resultados bastante aproximados com relação às concentrações encontradas dos adulterantes nas formulações. Ainda não existe uma regulamentação unificada estabelecida pelos órgãos governamentais para o controle de produtos fitoterápicos. Cada país tem a sua legislação, porém a comercialização destes produtos é globalizada. Talvez por isso a adulteração de produtos naturais vem sendo uma prática recorrente em diversas partes do mundo. Logo, uma regulamentação efetiva para os produtos de origem natural, pode resultar na redução destas infrações, ou punição dos infratores, garantindo assim os direitos dos consumidores de realizar um tratamento de qualidade, seguro e eficaz, sem prejuízo à saúde.