Tesi sul tema "Laxatives"

Introduction Constipation is a common health problem, often self-diagnosed and self-managed with laxatives without healthcare professional involvement. To improve diagnosis and management, it is important to understand constipation prevalence, associated factors, and laxative utilisation among community-dwelling adults. Aim The research aimed to determine the prevalence of constipation and laxative use, to investigate factors associated with constipation and describe laxative utilisation in Australia. Methods The first part explored constipation and laxative use in the general adult population. A cross-sectional survey was conducted online using a large nationally representative sample. The study focused on constipation prevalence, associated factors and laxative utilisation as well as examining the impact of constipation definitions on prevalence. The second part explored constipation and laxative use in an older adult cohort. Using Australian Longitudinal Study of Ageing data, the prevalence of constipation, associated factors and laxative use were examined over time. Results The online survey was completed by 2,024 participants. The constipation definition had considerable impact on prevalence estimates. As per Rome III criteria, 24% of participants had chronic constipation. Ten factors were significantly associated with it. One third (37%) reported using laxatives for either constipation treatment or prevention with 56% using laxatives recommended by healthcare professionals. In the older adult study, 239 participants were followed for 11 years. Self-reported constipation (14% to 21%) and laxative use (6% to 15%) increased over this period. Conclusion Constipation and laxative use are common among community-dwelling adults. Increased healthcare professional involvement in diagnosis and management, particularly laxative choice and use, may improve health outcomes. Development of guidelines addressing laxative use for both treatment and prevention should be considered.

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 Â 0108) showed that the largest group Jalapa (0262 Â 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.

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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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 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.

A pesar de las extensas investigaciones durante las últimas décadas, la pancreatitis aguda (PA) continúa siendo un reto para el manejo clínico, con una importante carga de morbilidad, mortalidad y coste, cuando la enfermedad desencadena la disfunción de órganos y sistemas distantes. Por ello, cualquier tratamiento para reducir la severidad de la enfermedad podría mejorar el pronóstico de los pacientes. En este sentido, la presente Tesis Doctoral se ha centrado en la búsqueda de nuevas estrategias terapéuticas para la protección del órgano pancreático. El objetivo principal de esta Tesis Doctoral es estudiar el efecto protector del PEG35 en distintos modelos experimentales in vivo e in vitro de inflamación pancreática y, más concretamente: 1. Caracterizar los mecanismos de protección del PEG35 en un modelo experimental de pancreatitis aguda necrotizante en rata. 2. Analizar los efectos de la administración de PEG35 en un modelo experimental de pancreatitis aguda edematosa intersticial en rata. 3. Evaluar la respuesta del PEG35 frente a la inflamación y la muerte celular en células acinares pancreáticas. 4. Analizar el efecto del PEG35 en la modulación de la inflamación mediada por exosomas.

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.

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Várias espécies de Senna são bastante conhecidas por suas propriedades terapêuticas, sendo utilizadas na medicina popular para o tratamento de inflamação na garganta e constipação. Neste estudo, foram avaliadas algumas propriedades biológicas e farmacológicas das folhas de Senna macranthera como as atividades anti-inflamatória, laxativa, sobre motilidade intestinal, antimicrobiana e antioxidante. A triagem fitoquímica do seu extrato metanólico e partições permitiu a identificação de compostos fenólicos como flavonoides, taninos e cumarinas na maioria das amostras, com exceção da partição em hexano, que apresentou antronas, triterpenos e esteroides em sua composição. O perfil cromatofráfico obtido por CLAE mostrou a presença da antraquinona emodina em todas as amostras. A partição em hexano reduziu significativamente o edema de pata induzido pela carragenina em ratos, de maneira similar ao diclofenaco de sódio. Atividade laxativa comparável ao padrão bisacodil foi observada para o extrato em metanol e partição em hexano, porém somente o último aumentou a motilidade intestinal. Além disso, o extrato metanólico e partições foram avaliados quanto a sua atividade antioxidante e a partição em acetato de etila apresentou pronunciada atividade, comparável ao padrão rutina. Significativa atividade antibacteriana sobre Pseudomonas aeruginosa também foi encontrada para o extrato em metanol e partição em hexano. Não foi observada citotoxidade para Artemia salina ou espécies de Leishmania para nenhuma amostra.
Several species of Senna are well known for their therapeutic properties, being used in the folk medicine to treat throat inflammation and constipation. In this study, an attempt was made to evaluate some biological and pharmacological properties of Senna macranthera leaves. In this regard, the anti-inflammatory, the laxative and the intestinal motility effects, and also the antimicrobial and antioxidant activities of its methanolic extract and partitions were determined. The phytochemical screening allowed the identification of phenolic compounds like flavonoids, tannins and coumarins in the majority of the extracts except for the hexane one which presented anthrones, triterpenes and steroids in its composition. The HPLC profile showed the presence of the anthraquinone emodine in all samples. The hexane partition significantly reduced carrageenan-induced paw edema in rats in a manner similar to that of sodium diclofenac. Laxative effect was observed for the methanolic extract and hexane partition comparative to the standard drug bisacodyl, however only the later increased the intestinal motility. Moreover, the samples were evaluated for their antioxidant activity and ethyl acetate partition presented a pronounced activity comparable to the standard rutin. Antibacterial activity against Pseudomonas aeruginosa was also found for metanolic extratct and hexane partition. No cytotoxicity against Artemia salina and Leishmania species were detected for any extracts.

BACKGROUND:Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density BMD] have not previously been investigated.METHODS:This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (greater than or equal to]2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI.RESULTS:Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95% confidence interval CI], 1.03-1.10) for falls, 1.02 (95% CI, 0.85-1.22) for hip fractures and 1.01 (95% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake.CONCLUSION:These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use.

La constipation est un symptôme précis, dont les étiologies sont exposées à la suite d'un rappel sur la physiologie du côlon. L'auteur étudie alors les diverses classes pharmacologiques de laxatifs et présente les spécialités commercialisées. Il évoque aussi l'abus de ces médicaments. Après quelques généralités sur le conseil à l'officine, une enquête réalisée dans cinq pharmacies de Côte-d'Or décrit notamment une automédicamentation fréquente de certaines classes de laxatifs. Elle dresse un profil des consommateurs et précise la nature des médicaments dispensés sur ordonnace. Enfin, l'auteur examine divers aspects de la pratique du conseil pharmaceutique dans ce domaine, au travers d'une vingtaine d'exemples issus de son expérience professionnelle. Il met ainsi en évidence le rôle actif de l'équipe officinale en matière de constipation et de laxatifs.

Resumo: Operculina macrocarpa (L.) Urb., Convolvulaceae, popularmente conhecida como batata-de-purga ou jalapa, é utilizada pela população como laxante e no tratamento da leucorréia. O objetivo deste trabalho foi realizar o controle de qualidade da droga vegetal, otimizar o processo extrativo desta espécie, avaliar a atividade laxante e antioxidante da raiz desta planta, realizar ensaios toxicológicos e ainda caracterizar fitoquimicamente a espécie por CLAE (Cromatografia Líquida de Alta Eficiência) e EM (Espectrometria de Massas). Foram realizados testes farmacopéicos de controle de qualidade, que comprovaram a autenticidade e a qualidade da droga vegetal. Avaliou-se a atividade laxante de O. macrocarpa através de diferentes modelos experimentais de trânsito intestinal utilizando o extrato hidroetanólico, o chá, a resina e os ácidos caféico, clorogênico e ferúlico. Verificou-se que o extrato hidroetanólico, o chá e os ácidos fenólicos apresentaram atividade laxante no modelo experimental avaliado e para atividade antioxidante foi observada uma discreta atividade para o extrato, o chá e a resina comparados com o padrão de ácido caféico. Na avaliação toxicológica o extrato hidroetanólico e o chá apresentaram uma diminuição nos valores das transaminases séricas AST (Aspartato aminotransferase) e ALT (Alanina aminotransferase), sugerindo hepatotoxicidade. Foi traçado o perfil químico do extrato hidroetanólico, do chá e da resina onde foram identificados os ácidos caféico, ferúlico, clorogênico, metil-ferúlico, quínico, dicafeoil-quinico e dímero do ácido caféico por CLAE e EM. Os ácidos fenólicos identificados foram quantificados por CLAE. Os resultados obtidos neste estudo químico-farmacológico de Operculina macrocarpa são fundamentais para o futuro desenvolvimento de um produto farmacêutico... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Operculina macrocarpa (L.) (Urb.), Convolvulaceae, popularly known as 'batata-depurga', is used by the population as a laxative and for the treatment of leucorrhea. The aim of this work was to carry out the quality control of vegetal drug, evaluate the antioxidant and laxative activity of the root of this plant, to carry out toxicology assays and phytochemical characterization by HPLC (High Performance Liquid Chromatography) and MS (Mass Spectrommetry) of this specie. Pharmacopeial tests of quality control had confirmed the authenticity and quality of sample. The laxative activity was evaluated by different experimental models for the hydromethanolic extract, tea, resin, and caffeic, chlorogenic and ferulic acid. The results showed that hydroethanolic extract, tea and phenolic acids had significant activity in experimental model tested. The results showed a little antioxidant activity for the extract, resin and tea when compared with standart caffeic acid. In the toxicological evaluation hydroethanolic extract and tea had presented alterations in the seric levels of transaminases ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) suggesting hepatotoxicity. Chemical profile of ethanolic extract, tea and resin was carried out by HPLC and MS and these techniques could identify caffeic, ferulic, chlorogenic, methylferulic, quinic, dicaffeoylquinic acids and a caffeic acid dimer. The phenolic acids were quantificated by HPLC. The results obtained in the chemical-pharmacological study of Operculina macrocarpa are fundamental for the future development of a pharmaceutical product with standarts of safety and efficacy... (Resumo completo clicar acesso electronic access below)
Orientador: Hérida Regina Nunes Salgado
Coorientador: Wagner Vilegas
Banca: Clélia Akiko Hiruma Lima
Banca: Luis Vitor Silva do Sacramento
Banca: Marco Vinícius Chaud
Banca: Dominique Corine Hermine Fischer
Banca: Hérida Regina Nunes Salgado
Doutor

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Universidade Estadual Paulista (UNESP)
Operculina macrocarpa (L.) Urb., Convolvulaceae, popularmente conhecida como batata-de-purga ou jalapa, é utilizada pela população como laxante e no tratamento da leucorréia. O objetivo deste trabalho foi realizar o controle de qualidade da droga vegetal, otimizar o processo extrativo desta espécie, avaliar a atividade laxante e antioxidante da raiz desta planta, realizar ensaios toxicológicos e ainda caracterizar fitoquimicamente a espécie por CLAE (Cromatografia Líquida de Alta Eficiência) e EM (Espectrometria de Massas). Foram realizados testes farmacopéicos de controle de qualidade, que comprovaram a autenticidade e a qualidade da droga vegetal. Avaliou-se a atividade laxante de O. macrocarpa através de diferentes modelos experimentais de trânsito intestinal utilizando o extrato hidroetanólico, o chá, a resina e os ácidos caféico, clorogênico e ferúlico. Verificou-se que o extrato hidroetanólico, o chá e os ácidos fenólicos apresentaram atividade laxante no modelo experimental avaliado e para atividade antioxidante foi observada uma discreta atividade para o extrato, o chá e a resina comparados com o padrão de ácido caféico. Na avaliação toxicológica o extrato hidroetanólico e o chá apresentaram uma diminuição nos valores das transaminases séricas AST (Aspartato aminotransferase) e ALT (Alanina aminotransferase), sugerindo hepatotoxicidade. Foi traçado o perfil químico do extrato hidroetanólico, do chá e da resina onde foram identificados os ácidos caféico, ferúlico, clorogênico, metil-ferúlico, quínico, dicafeoil-quinico e dímero do ácido caféico por CLAE e EM. Os ácidos fenólicos identificados foram quantificados por CLAE. Os resultados obtidos neste estudo químico-farmacológico de Operculina macrocarpa são fundamentais para o futuro desenvolvimento de um produto farmacêutico...
Operculina macrocarpa (L.) (Urb.), Convolvulaceae, popularly known as 'batata-depurga', is used by the population as a laxative and for the treatment of leucorrhea. The aim of this work was to carry out the quality control of vegetal drug, evaluate the antioxidant and laxative activity of the root of this plant, to carry out toxicology assays and phytochemical characterization by HPLC (High Performance Liquid Chromatography) and MS (Mass Spectrommetry) of this specie. Pharmacopeial tests of quality control had confirmed the authenticity and quality of sample. The laxative activity was evaluated by different experimental models for the hydromethanolic extract, tea, resin, and caffeic, chlorogenic and ferulic acid. The results showed that hydroethanolic extract, tea and phenolic acids had significant activity in experimental model tested. The results showed a little antioxidant activity for the extract, resin and tea when compared with standart caffeic acid. In the toxicological evaluation hydroethanolic extract and tea had presented alterations in the seric levels of transaminases ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) suggesting hepatotoxicity. Chemical profile of ethanolic extract, tea and resin was carried out by HPLC and MS and these techniques could identify caffeic, ferulic, chlorogenic, methylferulic, quinic, dicaffeoylquinic acids and a caffeic acid dimer. The phenolic acids were quantificated by HPLC. The results obtained in the chemical-pharmacological study of Operculina macrocarpa are fundamental for the future development of a pharmaceutical product with standarts of safety and efficacy... (Resumo completo clicar acesso electronic access below)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
The studed Herbal Product is indicated for treatment of intestinal colic and constipation, though there are no scientific data, that prove its efficacy. Thus, this study aimed in preclinical pharmacologic trials to evaluate its laxative and spasmolytic action and elucidate its possible pathway. For this, pharmacological tests were carried out in vivo to evaluate its stimulating effect on the gastrointestinal tract and in vitro assays in order to evaluate its spasmodic activity. The Herbal Product increased small intestinal motility in male mice at doses of 100mg/kg (161.66 ± 14.86%, n=6) and 200mg/kg (151.04 ± 17.17%, n=6) compared to control (100.00 ± 10.49%, n=6). The intestinal transit of animals constipated by loperamide (3mg/kg/day, three days) was reduced to 66.25 ± 7.49% (n=8) compared to the control group (100 ± 5.16%, n=8). In the constipated animals treated with doses of 100 and 200mg/kg (98.42 ± 6.33%, n=7) (99.32 ± 8.47%, n=7) was observed the normalization of the traffic bowel. Similar results were observed for 24 hours in the quantification of rat feces constipated by loperamide (3mg/kg/day, three days). The herbal medicine induced return of quantity of feces normal levels (7.92 ± 1.01g, n=6) in constipated animals (4.01 ± 1.43g, n=6), at dose of 100mg/kg (11.24 ± 2.90g, n=6) and 200mg/kg (8.70 ± 2.01g, n=6). These results demonstrate the stimulating action of this preparation in the intestine of the animals with potential laxative effect. Adding increasing and cumulative (0.01-1000μg/mL) of this product did not significantly alter spontaneous contractions in guinea pig ileum. However, its addition (1-1000μg/mL) caused a relaxation in this organ pre-contracted with 1μM carbachol, Emax= 67.61 ± 6.25%; EC50 269.77μg/mL (215.8 to 337.1), n=6; histamine 1μM (Emax= 58.68 ± 7.17%, EC50= 144.10μg/mL (86.65 to 239.70), n=6, and 40mM KCl (Emax= 50.76 ± 3.79%; EC50= 91.94μg/mL (57.97 to 145.80), n=7, no significant difference in the powers, suggesting an action of this product on a step common to these three agents. The relaxing action of this preparation was attenuated in ileum pre-contracted with 60mM KCl (Emax= 39.28 ± 1.95%, n=7) and the efficacy and potency were also significantly attenuated in the presence of potassium channel blockers, 5mM TEA, Emax= 22.79  2.99%; EC50 93.41μg/mL (54.89 to 159.00), n=5; and 5mM CsCl; Emax= 29.44  6.24%, EC50= 112,60μg/mL (44.09 to 287.80), n=5, suggesting the participation of these channels in relaxation. In contractions induced by 300nM S(-)BayK-8644, Cav channel agonist, the effect induced by phytomedicine, Emax= 39.28 ± 1.95%, EC50= 199.70μg/mL (120.50 to 239.00), n=8, was significantly lower when compared to carbachol, indicating the involvement of Cav in its effect. In preparations pre-incubated with 1μM propranolol (Emax= 34.45 ± 4.97%, n=6), the Emax was attenuated, suggesting also the involvement of β-adrenergic receptors in the effect induced by preparation. Thus, we conclude that the Herbal Product acts stimulating the intestine of rats and mice, especially in constipated animals and has spasmolytic activity in guinea pig ileum probably due to opening of K+ channels, inhibition of Ca2+ channels and activation of β-adrenoceptor.
O Produto Fitoterápico estudado é indicado no tratamento de cólicas intestinais e constipação, entretanto não apresenta dados científicos que comprovem sua eficácia. Assim, este estudo objetivou realizar ensaios farmacológicos pré-clínicos para avaliar sua ação laxante e sua ação espasmolítica, bem como elucidar seu provável mecanismo de ação. Para tal, realizaram-se ensaios farmacológicos in vivo para avaliar seu efeito estimulante sobre o trato gastrointestinal e ensaios in vitro com o intuito de avaliar sua atividade espasmolítica. O Produto Fitoterápico aumentou a motilidade do intestino delgado em camundongos machos, nas doses de 100mg/kg (161,66 ± 14,86%; n=6) e 200mg/kg (151,04 ± 17,17%, n=6) quando comparados ao controle (100,00 ± 10,49%; n=6). O trânsito intestinal de animais constipados por loperamida (3mg/kg/dia, três dias) foi reduzido a 66,25 ± 7,49% (n=8) em comparação ao grupo controle (100 ± 5,16%; n=8). Nos animais constipados e tratados com doses de 100 e 200mg/kg (98,42 ± 6,33%, n=7); (99,32 ± 8,47%; n=7), observou-se a normalização do trânsito intestinal. Resultados semelhantes foram encontrados na quantificação por 24 horas de fezes de ratos constipados por loperamida (3mg/kg/dia, três dias), em que o Produto Fitoterápico induziu o retorno da quantidade de fezes a níveis normais (7,92 ± 1,01g; n=6) de animais constipados (4,01 ± 1,43g; n=6), tanto na dose de 100mg/kg (11,24 ± 2,90g; n=6) como na dose de 200mg/kg (8,70 ± 2,01g; n=6). Estes resultados demonstram a ação estimulante da preparação estudada no intestino destes animais com potencial efeito laxante. A adição crescente e cumulativa (0,01-1000μg/mL) deste produto não alterou significativamente as contrações espontâneas em íleo de cobaia. Entretanto, sua adição (1-1000μg/mL) promoveu relaxamento neste órgão pré-contraído com carbacol 1μM, Emax= 67,61 ± 6,25%; CE50 269,77μg/mL (215,8 337,1); n=6, com histamina 1μM, Emax= 58,68 ± 7,17%; CE50= 144,10 μg/mL (86,65 239,70); n=6, ou com KCl 40mM, Emax= 50,76 ± 3,79%; CE50= 91,94μg/mL (57,97 145,80); n=7, não apresentando diferença estatística nas potências, o que sugere uma ação sobre uma etapa comum a estes três agentes. A ação relaxante desta preparação foi atenuada em íleo pré-contraído com KCl 60mM (Emax= 39,28 ± 1,95%; n=7) e sua eficácia e potência também foram significantemente atenuados na presença de bloqueadores de canais para K+, 5mM TEA, Emax= 22,79  2,99%; CE50 93,41μg/mL (54,89 159,00); n=5, e 5mM CsCl, Emax= 29,44  6,24%; CE50= 112,60μg/mL (44,09 287,80); n=5, sugerindo participação destes canais em seu relaxamento. Em contrações induzidas por 300nM S(-)-BayK 8644, agonista de canais Cav, o efeito induzido pelo Produto Fitoterápico Emax= 39,28 ± 1,95%; CE50= 199,70μg/mL (120,50 239,00); n=8, foi significativamente menor, quando comparado ao carbacol, indicando a participação dos Cav em seu efeito. Em preparações pré-incubadas com 1μM propranolol (Emax= 34,45 ± 4,97%; n=6), o Emax foi atenuado, sugerindo também a participação de receptores β-adrenérgicos no efeito induzido pela preparação. Assim, concluimos que o Produto Fitoterápico age estimulando o intestino de ratos e camundongos, principalmente em animais constipados e apresenta atividade espasmolítica em íleo de cobaia provavelmente pela abertura de canais para K+, inibição de canais para Ca2+ e ativação de β-adrenoceptores.

碩士
國立臺灣海洋大學
食品科學系
104
Phenolphthalein has been used as a drug for the treatment of constipation. Animal experiments show that phenolphthalein is carcinogenic and genotoxic. It can cause genetic damage of p53 tumor suppressor. Using phenolphthalein as a drug or adding it to the health functional food may be harmful to the human health. At present, many countries, including Taiwan, the United States, Japan, Canada, and some European countries prohibit the sale of laxative or health functional food which contains phenolphthalein. Different extraction conditions were tried to extract phenolphthalein from laxatives and health functional food. An optimal analytical procedure was also established for quantification of phenolphthalein by the use of high performance liquid chromatograph (HPLC) along with photodiode array (PDA) detector. Commercial laxatives and health functional food were analyzed with the procedure established in this research to see if phenolphthalein was added. An InertSustain® C18 column was used and the detector wavelength was set at 228 nm. A mobile phase of acetonitrile/water (45:55, v/v) isocratically eluted the analyte. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.0192 and 0.0638 ppm, respectively. Samples were extracted by ultrasonic assisted extraction (UAE) method and microwave assisted extraction (MAE) method, respectively. The optimum extraction condition for phenolphthalein tablet was to perform ultrasonic assisted extraction for 5 minutes. The recovery of phenolphthalein was 86.7 (± 0.1) ~ 95.8 (± 0.1)%. The optimum extraction condition for health functional food powder A was to perform microwave assisted extraction with the power of 200 W for 2 minutes. The recovery of phenolphthalein was 80.43 (± 0.04) ~ 96.13 (± 0.03)%. The optimum extraction condition for health functional food powder B was to perform ultrasonic assisted extraction for 45 minutes. The recovery of phenolphthalein is 84.0 (± 0.2) ~ 94.0 (± 0.2)%. The results showed that illegal addition of phenolphthalein still exists in the domestic market. Determination of phenolphthalein content of the health functional food should be strengthened in order to ensure the food safety.

Postoperative ileus (POI) is characterised by impairment of bowel motility leading to a delayed return of gastrointestinal (GI) function. It is a common complication after major abdominal surgery, and its clinical features include nausea, vomiting, abdominal distension, and delayed passage of flatus and stool. It predisposes patients to malnutrition, wound failure, and pneumonia, and often requires invasive interventions that significantly impact patient recovery and experience. The occurrence of POI is one of the most important determinants of adverse patient outcome after surgery, often surpassing both preoperative comorbid risk profile and intraoperative factors in the magnitude of its effect on short and long term survival. Delayed return of GI function as a single complication has the largest overall impact on healthcare costs. We do not have cost figures for Australia, but the estimated annual cost in the United States of this complication is approximately $1.5 billion. POI or delayed return of gastro-intestinal function is not a normal or routine part of recovery after abdominal surgery. It arises in around 10-30% of patients and is increasingly regarded as a potentially preventable or treatable problem, the management of which is currently suboptimal. Most published and in-press research on this topic is almost exclusively focused on novel therapeutic medications to treat and prevent ileus. While some of these medications, such as Alvimopan and Prucalopride, may be promising in this regard, they tend to be quite expensive and currently not funded (nor approved) for use in Australia for this indication. There is a major knowledge gap, and significant variability, in the use of readily available “off the shelf” medications and techniques to improve the return of normal GI function. In particular, the use of simple laxatives has been largely overlooked and not subjected to scientific testing despite sporadic worldwide use. This thesis aims to examine the available evidence for laxative use in this clinical setting, document usage patterns in routine clinical practice, and establish their clinical effectiveness and safety profile. A five-step process was adopted to answer these questions. Firstly, a systematic scoping review of Enhanced Recovery After Surgery (ERAS) protocols used in colorectal surgery worldwide was conducted. Second, a systematic review of randomised trials evaluating the safety and efficacy of laxative use after major abdominal surgery was conducted. Third, a global survey to gauge surgeons’ preferences and practice regarding laxative use was undertaken to understand the reasons behind the varied uptake rates of these medications in routine clinical practice. Fourth, a retrospective cohort study was conducted in the colorectal unit at the Royal Adelaide Hospital (RAH), to document the safety and efficacy profile of laxative use in these patients. Finally, an open label randomised controlled trial (RCT) of the combination of simple stimulant and osmotic laxatives to reduce the duration of postoperative Ileus (POI) in patient’s undergoing colorectal surgery (STIMULAX trial) was conducted. Our research found that ERAS protocols commonly recommended laxatives as an intervention targeting POI and return of GI function, but the type and dose were inconsistent, and the evidence quoted was limited. The systematic review of RCT data revealed that while laxative use may result in an earlier passage of a stool after major abdominal surgery, it did not influence other postoperative recovery parameters. There was insufficient data to evaluate the safety profile of laxatives in this setting. Furthermore, this lack of high-quality evidence appeared to be the main reason why most surgeons do not routinely prescribe laxatives after elective colorectal surgery, as shown by the global survey we conducted. This survey also showed that there is wide variability in the type of laxatives used amongst those surgeons who do use laxatives. We then conducted an RCT on the risk-benefit of laxative use after elective colorectal surgery (STIMIULAX trial) to address the knowledge gap. The trial showed that patients receiving multimodal laxatives achieved earlier recovery of GI function after surgery, compared with a control group. There was no difference in major complications, length of stay, or any other key recovery parameters. This paved the way for our final Phase II study (PyRiCo-P). We investigated whether we could safely circumvent the autonomic dysfunction caused after surgery by administering oral Pyridostigmine to reduce the duration of postoperative Ileus after colorectal surgery. Fifteen patients were recruited, and none of the patients had any adverse events. We suggest the next step is to conduct a double-blinded randomised controlled trial to assess the efficacy of Pyridostigmine in this setting. This thesis contributes new evidence on therapeutic effectiveness of laxatives to reduce the duration of ileus after major abdominal surgery and has established a baseline framework upon which future trials of novel medications can be assessed.
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2021

碩士
國立臺灣大學
護理學研究所
88
Constipation is a common problem among elderly patients in hospital. Old age produces physiological changes, such as the decreased ability to chew, that lead to an alteration in dietary habits, and chronic illnesses that cause a limitation in physical activity. These factors put the elderly at risk of becoming constipated. Health care workers often prescribe laxatives without assessing the causes of constipation. Using laxatives in this way does not only fail to solve the constipation problem, but is also a waste of medical resources. References on this topic suggest investigation related to constipation has been relatively sparse in Taiwan. Hence, the objectives of this study were: (1) To investigate the relationships between, demographic characteristics, health status, risk factors and the occurrence of constipation; (2) To investigate the use of laxatives in the hospitalized elderly. This was a longitudinal study that investigated people aged 65 years and over, who had had no chronic constipation within three months before admission in six wards of a tertiary medical center in Taipei. Subjects were investigated using 4 questionnaires composed by the researcher. First, subjects were selected using "The questionnaire of pre-admission bowel movements". On the 4th day of admission or upon the occurrence of constipation, the researcher collected data using "The survey of bowel movements during hospitalization II - risk factors". Data was then collected everyday using "The survey of bowel movements during hospitalization I". When the subjects received laxatives, their data were collected everyday using "The survey of bowel movements during hospitalization III - management and outcome". The results of this study showed that: 1. Fifty subjects (33%) of the 152 respondents had constipation during hospitalization, 38 subjects (25.0%) did not have a bowel movement for more than 3 days, and 12 subjects (7.9%) passed hard stools. One hundred and two subjects did not have constipation. 2. A stepwise logistic regression model showed that the hospitalized elderly who consumed 6g or less of dietary fiber were 6.21 times more likely to develop constipation than those who consumed more than 6g of dietary fiber (95% CI 1.97 to 19.63). Bedridden elderly were 3.47 times more likely to suffer from constipation than those who ambulated independently (95% CI 1.44 to 8.35). Elderly who did not receive antacid which contained aluminum and magnesium were 3.60 times more likely to develop constipation than those who did (95% CI 1.52 to 8.54). Other variables, for example; sex, age, number and category of diseases, fluid intake, non-laxatives drugs, constipation inducing drugs and so on were not shown to be statistically significant. Although older patients and patients who did not use NSAIDs tended to have constipation, the tendency did not prove to be statistically significant. 3. During hospitalization, MgO (46.7%) was most commonly administered, followed by Bisacodyl suppositories (31.6%). Sixty-six subjects received prophylactic laxatives, but among them 18 still suffered from constipation. Prophylactic laxatives did not completely prevent the occurrence of constipation in the subjects who received them. 4. Of the 95 subjects who received laxatives, results showed that 29 subjects (30.5%) had diarrhea and 7 subjects (7.7%) had fecal incontinence. The relationship between subjects who had diarrhea and fecal incontinence and the use of laxatives was statistically significant (p=0.016, p=0.038). Subjects who received laxatives had a higher tendency to develop diarrhea and fecal incontinence. 5. During the subject recruitment, 58 patients were excluded because they did not meet selection criteria. By comparing the baseline variables of the respondents who met the selection criteria with those who did not, the results showed that subjects who experienced chronic constipation tended to have a greater number of diseases and were more often diagnosed to have Parkinsonism and diabetes mellitus. There were no statistical differences between age, sex, and education in either group. The results revealed that about one third of the elderly patients who did not have a history of constipation prior to hospitalization developed constipation in hospital. Elderly patients who consumed less than 6g of dietary fiber and who were bedridden had a greater tendency to develop constipation. Prophylactic laxatives did not completely prevent the occurrence of constipation and the use of laxatives increased the tendency to develop diarrhea and fecal incontinence. The findings of this study may help nurses to; understand the problem of constipation among the hospitalized elderly, screen and detect the high-risk groups early to prevent the occurrence of constipation, provide appropriate intervention and implement professional nursing in order to increase the quality of life among elderly patients, and reduce the waste of medical resources.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
A obstipação é um distúrbio gastrointestinal comum com um impacto significativo na qualidade de vida dos idosos e na gestão dos recursos de saúde, sendo assim considerado um problema de saúde pública. Devido à falta de uniformidade de critérios diagnósticos, a prevalência da obstipação varia entre os diferentes estudos epidemiológicos. É, contudo, consensual que se trata de uma condição clínica comum na população geral, cuja prevalência é maior na população idosa. É importante salientar que a obstipação não é uma consequência fisiológica do processo de envelhecimento e que a sua predominância nesta faixa etária tem como contributos a presença de condições médicas crónicas, o uso de medicação crónica, alterações na dieta e estilo de vida, anomalias estruturais no intestino, hipossensibilidade retal e fraqueza dos músculos abdominais e do pavimento pélvico. Questões psicossociais e comportamentais também são importantes no desenvolvimento da obstipação. A apresentação clínica da obstipação em idosos parece ser diferente de outras populações, relatando mais frequentemente sintomas de defecação difícil. As principais complicações da obstipação em idosos são a impactação e a incontinência fecais. As recomendações para o tratamento da obstipação seguem uma abordagem gradual. Após uma história clínica e um exame físico completo, na ausência de sinais de alarme e de causas secundárias de obstipação, a abordagem correta do idoso obstipado passa pelo tratamento não farmacológico. Caso os pacientes não respondam a este tratamento, a administração de laxantes de volume, laxantes osmóticos, laxantes estimulantes e agentes secretores deve ser feita de forma sequencial. Uma abordagem de tratar e testar é prática e económica. Apenas em idosos com obstipação refratária ao tratamento, alguns testes funcionais são úteis para esclarecer a etiologia da obstipação. Se nestes for identificada uma defecação dissinérgica o biofeedback é o tratamento de escolha. Em última linha, a cirurgia pode ser uma opção, tendo em conta as altas taxas de morbilidade e mortalidade associadas a pacientes com idade avançada.Agentes mais recentes com alvos fisiológicos específicos provaram ser eficazes em adultos com obstipação crónica, no entanto, faltam dados sobre o seu perfil de segurança em idosos. A falta de evidências de alta qualidade sobre a segurança e eficácia dos laxantes em idosos é problemática, pois esta é a população com maior necessidade de tratamento seguro e eficaz da obstipação.
Constipation is a common gastrointestinal disorder with considerable impact on quality of life of the elderly and on the health expenses, thus being considered a public health problem. Due to the lack of uniform diagnostic criteria, the prevalence of constipation varies between different epidemiological studies. However, it is consensual that is a common clinical condition in the general population, witch prevalence is higher in the elderly population. It is important to point out that constipation is not a physiological consequence of normal aging and that the predominance in this age group is a result of chronic medical conditions, chronic medication use, changes in diet and lifestyle, intestinal structural abnormalities, rectal hyposensitivity and weakness of abdominal and pelvic floor muscles. Psychosocial and behavioral issues are also important in the development of constipation. The clinical presentation of constipation in the elderly appears to be different from other populations, the elderly report more often difficult stool passage. The main complications of constipation in the elderly are faecal impaction and faecal incontinence. Recommendations for the treatment of constipation follow a stepwise approach. After a clinical history and a complete physical examination, in the absence of alarm signs and secondary causes of constipation, the correct approach for the constipated elderly goes through non-pharmacological treatment. If patients do not respond to this treatment, the administration of bulking forming laxatives, osmotic laxatives, stimulating laxatives and secretagogues should be performed sequentially. A treat and test approach is practical and economical. Only in the elderly with constipation refractory to treatment, some functional tests are useful to clarify the etiology of constipation. If dyssynergic defecation is identified, biofeedback is the treatment of choice. Ultimately, surgery may be an option, taking into account the high rates of morbidity and mortality associated with elderly patients.Newer agents with specific physiologic targets have proven to be effective in adults with chronic constipation, but data is lacking for safety profile in the elderly. The lack of high-quality evidence of the safety and effectiveness of laxatives in older adults is problematic as this is the population with the highest need for safe and effective management of constipation.

Abstract Laxatives appear to be one of the most common group of drugs sold in retail pharmacy presently. Use of these drugs appears to be by all patients regardless of age, gender, race, education level and income group. Reasons for ingestion of laxatives also appear to vary among patients. This study investigated patients wishing to purchase laxatives from a suburban pharmacy in Johannesburg located near the inner-city. It clarified the patient’s own perception of what constipation is, why he or she ingested this formulation and for how long this product had been used. The study also reviews adverse effects that patients experienced using these products. Following the exclusion criteria, the sample size totaled 197. Data was collected over a period of ten weeks from February 2006 until April 2006, in which patients wishing to purchase laxatives were asked to complete a confidential questionnaire regarding their use of laxatives. Results obtained revealed that there is widespread misuse of laxative products amongst the patients questioned. A large percentage of patients (66%) were not in their own opinion constipated and were using laxatives for purposes other than for which these products are indicated. Many patients (71%) are ignorant as to normal frequency of bowel habits, and 81% of patients were using laxatives to treat conditions other than constipation. An encouraging aspect of this study showed that with appropriate education and drug control, many patients could be taught to treat their medical conditions more correctly than by using a laxative as a generalized detoxification product to cure all illnesses.

碩士
義守大學
醫務管理學系
104
Purpose: Cancer is the leading cause of death worldwide. Accurate localization of malignant tumor is the important part of treatment planning for the patient of cancer. Fluorine-18- fluorodeoxy glucose (18F-FDG) positron emission tomography/computed tomography (18F-FDG PET/CT) has been proved useful for the detection, staging and restaging of several malignancies. Unfortunately, 18F-FDG PET/CT PET / CT still could not avoid the false positives and false negatives. There are some organs and tissues will have high uptake of 18F-FDG and cause false positive result, such as the inflammatory tissue, genitourinary tract, intestine, muscle, and so on. The reason of intestinal uptake of 18F-FDG may be due to constipation, increased peristalsis of gastrointestinal tract or contraction of intestinal smooth muscle. Therefore, we try to use laxatives to reduce those conditions and hope to decrease intestinal uptake of 18F-FDG. If we can use this method to reduce the intestinal uptake of 18F-FDG and eliminate the false positive of image before examination, it will assist physician to solve the difficulties of image diagnosis. Materials and Methods: In this study, we collect 202 subjects to divide into“ not taking laxatives group” and “taking laxatives group”. There are 109 people not taking laxatives and 93 people taking laxatives. Through the physicians of the nuclear medicine who are experienced diagnose. We count the SUV value of colon, descending colon, sigmoid colon and rectum. Then we generalize following three points: 1. Whether the gender will affect the value of each intestinal SUV. 2. Whether the age will affect the value of each intestinal SUV. 3. Whether the taking laxatives will affect the value of each intestinal SUV. The use of positron scanned images plus physiological functions of human anatomy and CT images provided interpretation of 18F-FDG in the body''s metabolic profile, using laxatives (Klean-prep), and reduce shrinkage caused by constipation or intestinal smooth muscle increase intestinal motility caused by 18F-FDG uptake increased pharmaceutically active, in order to reduce the intake of intestinal physiology, the statistical software SPSS2 descriptive statistical analysis of the distribution of the various variables. Finally, we use nonparametric analysis Kruskal Wallisru and Mann-Whitney U to confirm. Result: We use Mann-Whitney U (P <0.05) to test whether that gender will affect the uptake of intestinal SUV values. We found between gender and among the various intestinal SUV max all are> 0.05, regardless of whether they have used laxatives. It proves that gender does not interfere with their intestinal uptake between the SUV. It can be found that the age does not affect the reading in the intestinal SUV. We use Kruskal Wallisru test (P <0.05) to judge whether age would be interference between the value of its SUV intestinal uptake. The group is divided into three age groups, regardless of whether they have used laxatives, then we found age and among intestinal P value SUV mas between all are> 0.05. It shows that the age does not interfere with their gut SUV between intake. It can be found that the age does not affect the reading in the intestinal SUV. We use Mann-Whitney U test (P <0.05) to judge whether it would interfere with the use of laxatives affect uptake among its various intestinal SUV max values. We found between the use of laxatives and various intestinal P value SUV max are all <0.05. Unused laxatives liver SUV max (SUV max: 2.6 ± 0.3) and thigh SUV max (SUV max: 0.9 ± 0.1) and liver SUV max (SUV max: 2.6 ± 0.3) after use of laxatives and thigh SUV max (SUV max: 0.9 ± 0.1). There were no specific changes in the value of each group. It can be understood that the use of laxatives does not affect the intake of other organs SUV max values. In addition, the use of laxatives can really improve the uptake of intestinal SUV values uptake SUV max values significantly decreased (P <0.05). Thus verifiable, laxatives can make use of intestinal SUV value decreased to reduce SUV max value due to the contraction of smooth muscle of the intestinal motility and constipation and intestinal tract caused by increased and improved intestinal qualitative images.

碩士
中國醫藥學院
醫學研究所
90
According to the chinese medical literature, C. teeta Walich, Fraxini cortex, Goldenseal, Sophora flavescens Aiton, and Phellodendron amurense Rurp are known for the anti-diarrheal characteristics, whereas Rheum palmatum L., Croton tiglium L., Cannabis sativa L. and Pharbitis hederacea Choisy are known for the ability to promote diarrhea. This study was aimed to discern effects of these herbs’ extracts on ion transport of the rat intestinal epithelia. The epithelia were mounted in the Ussing chamber and were attached to voltage/current clamp for measuring changes of the short circuit current. After serosal addition of 5μM forskolin to raise the current, ethanol-extracts and water-extracts of the herbs with anti-diarrheal characteristics did reduce the current. On the contrary, ethanol-extracts and water-extracts of the herbs with diarrhea-promoting characteristics augmented the current further. Moreover, ethanol-extracts of these herbs showed more effect on changing the current. In following experiments, ouabain and bumetanide, which inhibit Na+-K+-ATPase and Na+-K+-2Cl- cotransporter respectively, were added prior to ethanol-extracts of these herbs for revealing the herb’s effect on Na+ and Cl- movement. The results suggest Fraxini cortex, Rheum palmatum L. and Croton tiglium L.，Cannabis sativa L. would affect Cl- transport, whereas Sophora flavescens Aiton would affect Na+ transport. This study provide evidences to confirm that changes of Cl- or Na+ transport may be involved in cellular activities of the anti-diarrheal and diarrhea-promoting herb medicines on the rat intestinal epithelia.

Tese de mestrado, Medicamentos à Base de Plantas, Universidade de Lisboa, Faculdade de Farmácia, 2012
Atualmente devido ao aumento das taxas de obesidade observadas em todo o mundo e, consequentemente em Portugal e do impacto clínico e social sentido por cada indivíduo por deter um índice de massa corporal elevado, não é de estranhar o incremento do uso de produtos de saúde à base de plantas, quer como medicamentos tradicionais à base de plantas quer como suplementos alimentares, em regimes dietéticos conducentes à perda de peso. Alguns destes produtos de saúde são misturas complexas constituídas por diferentes fármacos vegetais dotados, entre outras, de atividade diurética e/ou laxativa, e sendo sene, folha e/ou sene da Índia, fruto e sene de Alexandria fruto, dos fármacos laxativos mais comumente utilizados. Os problemas de qualidade e segurança da utilização deste tipo de produtos de saúde à base de plantas são uma realidade a que não é alheio o facto da maioria destes continuar a ser comercializada em Portugal sem autorização de introdução no mercado por parte do INFARMED - Autoridade Nacional do Medicamento e Produtos de Saúde, I. P.. Entre os problemas descritos citase a título de exemplo, a introdução ilícita de fármacos de síntese, usados como ansiolíticos, sedativos ou hipnóticos, antidepressivos, diuréticos ou como estimulantes inespecíficos do Sistema Nervoso Central. Com a realização do presente estudo, pretendeu-se avaliar a qualidade dos oito produtos de saúde à base de sene, folha e/ou sene da Índia, fruto e/ou sene de Alexandria fruto, mais comumente comercializados na região de Lisboa. Para o efeito, foram usadas as monografias constante na Farmacopeia Portuguesa 9, relativas a estes fármacos, e que incluem ensaios de identificação botânica e química, ensaios de pureza, doseamento e ensaios farmacotécnicos. Procurou-se também avaliar a qualidade da informação disponibilizada nos rótulos dos produtos, de acordo com legislação atual. Este trabalho apresenta ainda um estudo de pesquisa de fármacos adulterantes por cromatografia em camada fina. Foi ainda desenvolvido e validado um método de Cromatografia Líquida de Alta Pressão para o doseamento do senósido A e do senósido B, adaptado às diferentes amostras em análise. Os resultados dos ensaios de Identificação botânica e química mostraram a existência de sene, folha e/ou sene da Índia, fruto e/ou sene de Alexandria fruto em todas as amostras (100%), apresentando no entanto 75% destas amostras erros de rotulagem. Verificou-se ainda que 25% das amostras continham matéria estranha, tendo 12,5% das amostras um valor de cinzas totais e 25% das amostras apresentaram um valor de cinzas insolúveis (em ácido clorídrico) superior ao valor limite. A totalidade das amostras mostrou concentrações totais de derivados di-hidroxiantracénicos expressos em senósido B, abaixo do teor mínimo permitido (entre 0,23% e 2,32%). Os resultados farmacotécnicos mostraram não estar, 2 amostras, em concordância com o ensaio de uniformidade de massa. 27,7% dos produtos analisados estavam adulterados com fenolftaleína e diazepam. Em conclusão, a totalidade dos produtos analisados mostrou não estar em conformidade com as especificações de qualidade exigíveis para estes, enquanto produtos de saúde à base de plantas.