Observações clínicas e dados experimentais sugerem que o tratamento com antidepressivos em pacientes psiquiátricos e voluntários saudáveis está associado a efeitos extraterapêuticos que, em pacientes, independem da melhora da sintomatologia preexistente. Tais efeitos incluem aumento da autoconfiança, melhora do humor e do bem-estar; diminuição da irritabilidade, aumento da tolerância a estímulos aversivos, etc. Embora observados em uma parcela significativa de indivíduos, a natureza e a intensidade dessas mudanças na resposta emocional induzida por antidepressivos nunca foram descritas detalhadamente. Objetivos: a) Descrever os aspectos fenomenológicos da alteração da resposta emocional pelo uso de antidepressivos em voluntários sadios e pacientes; b) avaliar o efeito da clomipramina sobre a irritabilidade induzida artificialmente em voluntários sadios. Métodos: Foram selecionadas duas amostras: a) 54 sujeitos sem história pessoal e familiar de transtornos psiquiátricos (triados através do Questionário de Rastreamento Psiquiátrico-20, da Entrevista Clínica Estruturada para o Manual Diagnóstico e Estatístico de Transtornos Psiquiátricos - SCID e de um questionário de história familiar; b) 20 pacientes com transtorno depressivo unipolar e transtornos da ansiedade que apresentassem relatos sugestivos de efeito extraterapêutico. Os voluntários saudáveis, após 4 semanas de clomipramina de 10 a 40 mg por dia, e os pacientes foram avaliados por meio de uma entrevista focal para checagem dos critérios de resposta (aumento da tolerância; eficiência; bem-estar; e sensação de estar diferente de seu habitual). Para a avaliação de irritabilidade, 48 voluntários sadios foram submetidos a um procedimento de indução de frustração (modelo sucesso-fracasso), antes e quatro semanas após o uso de clomipramina. Uma medida subjetiva de irritabilidade (Escala Analógica de Agressividade) foi aplicada antes e após o procedimento de indução de frustração. Resultados: 14 sujeitos saudáveis (30%) e os 20 pacientes apresentaram melhora da resposta emocional que preenchia os critérios de resposta. Os relatos dos sujeitos e pacientes na entrevista focal foram de conteúdo muito semelhante. Os 14 voluntários (100%) e os 20 pacientes apresentaram diminuição da irritabilidade e tensão em interação social; a melhora de desempenho foi observada nos 14 voluntários sadios e em 16 (80%) dos pacientes; os 20 pacientes e 13 (93%) voluntários sadios relataram sensação de bemestar; os 14 voluntários e 18 pacientes (80%) sentiram-se muito diferentes de seu habitual. No procedimento de indução de irritabilidade, os voluntários com efeito extraterapêutico diferenciaram-se dos demais por apresentarem menor irritabilidade e sentimentos correlatos antes da administração de clomipramina. Conclusões: Os resultados sugerem que o efeito extraterapêutico ocorre em uma parcela dos sujeitos sadios e dos pacientes tratados com antidepressivos. Os efeitos se manifestam como uma diminuição na expressão de afetos negativos a eventos aversivos cotidianos, sem, no entanto, alterar os afetos positivos. A menor irritabilidade observada nos sujeitos sadios com critério de resposta no procedimento de indução de irritabilidade pode ser um preditor do aparecimento do efeito extraterapêutico / Clinical observations and experimental data suggest that the administration of antidepressants to psychiatric patients and normal volunteers is associated with extratherapeutic effects that in patients are independent of the preexistent symptomatology. These effects include increased self-confidence, better mood and well being, reduction in irritability, and increased tolerance to aversive stimuli. Although these effects are observed in a significant number of individuals, the nature and intensity of these changes in emotional mood induced by antidepressants were never described in detail. Objectives: a) To describe the phenomenological aspects of the emotional alterations in healthy volunteers and patients using antidepressants; b) to evaluate the effect of clomipramine on irritability artificially induced in healthy volunteers. Methods: We selected two samples: a) 54 subjects without personal or family history of psychiatric disorders (selected through the Self-Reporting Questionnaire-20, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - SCID, and a family history questionnaire; b) 20 patients with either unipolar depression or anxiety disorders whose reports were suggestive of extratherapeutic effects. After 4 weeks of clomipramine 10 to 40 mg daily, healthy volunteers and patients were evaluated through a qualitative interview for checking response criteria (increased interpersonal tolerance; efficiency; wellbeing; and feeling substantially changed from usual self). To evaluate irritability 48 subjects were submitted to a procedure to induce frustration (success-failure model) before and after the 4 weeks of clomipramine use. A subjective measure of irritability (Aggression Rating Scale) was applied before and after the frustration inducing procedure. Results: 14 healthy volunteers (30%) and 20 patients presented an improved emotional response according to the response criteria. Fourteen volunteers and 20 patients reported decreased irritability and tension in social interaction; improved performance was observed by the 14 healthy volunteers (100%) and 16 (80%) patients; 20 patients and 13 (93%) healthy volunteers reported a wellbeing sensation; 14 healthy volunteers and 18 (80%) patients reported feeling substantially changed from their usual. Volunteers that reach response criteria on the irritability induced procedure reported less irritability and correlate feelings before clomipramine administration than those who did not fulfill the criteria. Conclusions: The results suggest that the extratherapeutic effect occurs in a percentage of healthy volunteers and patients treated with antidepressants. The effects are manifested as a reduction in the expression of negative affect to aversive daily events, without modifying positive affects. Lower irritability observed on volunteers with response criteria on the induced frustration procedure could be a predictor for the occurrence of the extratherapeutic effect

Introdução: Rosiglitazone (RGL) é um ligante dos receptores PPAR e vem sendo usada no tratamento do Diabetes Mellitus tipo 2 e nas doenças inflamatórias. Mas, RGL pode reduzir a filtração glomerular (FG), a carga excretada de sódio na urina (UVNa) e aumentar a expressão da Na+,K+- ATPase na medula renal. Então, RGL pode causar edema e insuficiência cardíaca congestiva. Entretanto, não tem sido reportado se RGL pode induzir insuficiência renal aguda (IRA). Objetivo: Verificar se a redução da FG causada pelo tratamento com RGL predispõe à IRA em ratos. Avaliar em condições basais e de vasoconstrição renal e se há diferenças entre ratos normocolesterolêmicos (NC) e hipercolesterolêmicos (HC). Métodos: A FG foi medida pelo clearance de inulina no 8º dia em ratos (~200g) NC e HC tratados ou não com RGL (48 mg/kg/dieta) na situação basal e durante a infusão endovenosa de Ang II (40 ng/kg/min). Além disso, a atividade da Na+,K+-ATPase foi avaliada em homogenato renal em outra série de animais. Resultados: Na situação basal, NC e HC apresentaram FG semelhante e o tratamento com RGL reduziu a FG apenas em NC de 0,78±0,03 para 0,50±0,05* ml/min/100g, *p<0,001. Apesar da redução da FG, a UVNa em NC+RGL não se modificou. Durante a infusão de Ang II, a FG de NC, HC e HC+RGL reduziu-se para o mesmo patamar de NC+RGL e um significante aumento da UVNa foi observada apenas em NC+RGL (NC= 3,32±0,88; NC+RGL=5,86±1,04*; HC= 2,63±0,43 e HC+RGL= 2,23±0,39 uEq/min, *p<0,01). Além disso, RGL induziu aumento na atividade da Na+,K+-ATPase em HC+RGL e não modificou em NC+RGL. Os valores expressos em M Pi/mg proteína.h-1 foram de 45±7 em NC, 43±5 em NC+RGL, 48±7 em HC e 64±4* em HC+RGL, *p<0,05. Analisando todos os resultados em conjunto, a redução da FG associada com a alta natriurese e ausência da modulação da atividade da Na+,K+-ATPase em NC+RGL sugerem lesão renal neste grupo. Conclusão: Os mecanismos de ação da RGL diferem de acordo com a condição metabólica. Então, RGL deve ser prescrita com cautela na ausência de hipercolesterolemia e requer a monitoração da função renal principalmente nas situações de vasoconstrição / Introduction: Rosiglitazone (RGL) is a ligand for PPAR used to treat type 2 Diabetes Mellitus and inflammatory diseases. However, RGL can reduce the glomerular filtration rate (GFR), urinary sodium excretion (UVNa) and increase the expression of Na+, K+-ATPase in renal medulla. Thus, RGL may induce edema and congestive heart failure. However, acute renal failure (ARF) provoked by RGL treatment has not been reported. Aim: To test whether reduced GFR by RGL may predispose to ARF at baseline and during a renal vasoconstriction state, and if the findings differ between normocholesterolemic (NC) and hypercholesterolemic (HC) rats. Methods: GFR was measured by inulin clearance on the 8th day in NC and HC rats (~200g) treated or not with RGL (48 mg/kg diet) at baseline and during intravenous infusion of Ang II (40 ng/kg/min). Furthermore, the Na+,K+- ATPase activity was determined in renal homogenates in other series of animals. Results: At baseline, NC and HC had similar GFR and the treatment with RGL reduced GFR only in NC from 0.78±0.03 to 0.50±0.05* ml/min/100g, *p<0.001. Although GFR was reduced, UVNa was unchanged in NC+RGL. During Ang II infusion, GFR was significantly reduced in NC, HC and HC+RGL and it remained at the same reduced level in NC+RGL. At this time, when GFR was reduced the same range in all groups, a significant increment in UVNa was only observed in NC+RGL (NC = 3.32±0.88; NC+RGL = 5.86±1.04*; HC = 2.63±0.43 and HC+RGL = 2.23±0.39 Eq/min, *p<0.01). Moreover, RGL induced an increase in the activity of Na+, K+-ATPase in HC+RGL, but it did not modify the activity of this enzyme in NC+RGL. The values expressed in M Pi/mg.protein.h-1 were 45±7 in NC, 43±5 in NC+RGL, 48±7 in HC and 64±4* in HC+RGL, *p<0.05. Taken together, reduction in GFR associated with high natriuresis and without changes in the Na+, K+-ATPase activity in renal medulla of NC+RGL may suggest renal injury in this group. Conclusion: RGL may act distinctly in normocholesterolemia and in hypercholesterolemia. Thus, RGL may be prescribed with caution in absence of hypercholesterolemia and requires monitoring of renal function specially if a renal vasoconstriction state is associated.

Introdução. A varfarina tem sido considerada a principal terapêutica anticoagulante oral há aproximadamente 50 anos, estando entre os dez medicamentos mais envolvidos com reações adversas a medicamentos (RAM), apresenta estreita janela terapêutica e complexo regime posológico, exibe enorme variabilidade doseresposta e elevado risco de interações medicamentosas (IM). Objetivo. Identificar e avaliar as IM e RAM relacionadas com a administração da varfarina. Casuística e Métodos. Trata-se de um estudo transversal. Os dados foram coletados retrospectivamente através do banco de dados informatizado do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo pertencente ao Sistema Único de Saúde. As prescrições de janeiro/2004 a dezembro/2010 dos pacientes que utilizaram varfarina foram analisadas, sendo os pacientes divididos em dois grupos: estudo (uso de vitamina K até 168 horas após prescrição de varfarina) e controle. Posteriormente, as prescrições medicamentosas que não continham varfarina foram excluídas da análise. As informações coletadas incluíram idade, gênero, raça, unidade de atendimento, diagnóstico clínico, doses e medicamentos, e exames laboratoriais. As IM com varfarina foram classificadas em risco A, B, C, D e X de acordo a base de dados da Lexi-Interact(TM) Online. Foi realizada análise descritiva e analítica (p<0,05). Resultados e Discussão. Foram identificados 3048 pacientes, os quais receberam 154161 prescrições medicamentosas (42120 continham varfarina). A idade média foi de 55,8 (±19,3) anos, 53,2% do gênero feminino, prevalência de idosos (48,1%) e do diagnóstico outras doenças cerebrovasculares específicas (4,3%). Os valores médios da international normalized ratio (INR) (2,4±1,7) e dose de varfarina (5,1±1,8mg) encontraram-se dentro dos preconizados pelos protocolos terapêuticos. Foi observado que 66,4% dos pacientes realizaram uso de polifarmácia, o que pode elevar o risco de IM. Além disso, 63,2% dos pacientes apresentaram prescrição(ões) de medicamentos classificados como risco D e/ou X, com média de 1,4 (±0,4) medicamento/prescrição, destacando-se o ácido acetilsalicílico e amiodarona. Quando comparado grupo de estudo (n=429) versus controle (n=2619), houve diferença estatisticamente significativa na idade média (anos) (59,0±18,8 vs. 55,5±19,3; p<0,000), número médio de medicamentos/prescrição (7,1±2,8 vs. 6,2±2,8; p<0,000), número médio de medicamentos de Risco D e X de IM por prescrição (1,4±1,3 vs. 1,0±1,0; p<0,000), albumina sérica (g/dL) (3,4±0,6 vs. 3,7±0,6; p<0,000), aspartato aminotransferase (U/L) (60,7± 200,6 vs. 41,5±84,5; p<0,005) e INR (4,9±3,4 vs. 2,1±0,7; p<0,000), fatores estes que podem ter contribuído para ocorrência de RAM no grupo de estudo. Conclusão. Observou-se elevada ocorrência de possíveis IM e RAM nos usuários de varfarina, as quais podem comprometer a efetividade e segurança do tratamento farmacológico. Como possíveis fatores de risco para ocorrência de RAM, destacam-se elevados valores de idade, número de medicamentos/prescrição, prescrição de medicamentos classificados como risco D e/ou X, de INR e de aspartato aminotransferase, e valores diminuídos de albumina sérica. / Introduction. Warfarin has been considered the main oral anticoagulant therapy about 50 years ago and is among the ten drugs most commonly involved in adverse drug reactions (ADR), has a narrow therapeutic index and complex dosage regimen, exhibits enormous variability dose-response and high risk drug-drug interactions (DDI). Objective. To Identify and evaluate DDI and ADR related to the administration of warfarin. Casuistry and Methods. This was a cross sectional study. Data were collected retrospectively through the computerized database of the Faculty of Medicine of Ribeirao Preto Hospital, University of Sao Paulo linked to the Unified Health System. The prescriptions of the January/2004 to December/2010 of patients using warfarin were analyzed, and the patients were divided into two groups: study (utilization of vitamin K until 168 hours after prescribing warfarin) and control. Thereafter, the drug prescriptions that did not contain warfarin were excluded from analysis. Information collected included age, gender, race, patient service center, clinical diagnosis, dosages and drugs, and laboratory exams. The warfarin DDI were classified at risk A, B, C, D and X according to the database Lexi-Interact (TM) Online. Descriptive and analytical analysis were performed (p<0.05). Results and Discussion. We identified 3048 patients who received 154,161 drug prescriptions (42,120 contained warfarin). The mean age was 55.8 (±19.3) years, 53.2% female, prevalence of elderly (48.1%) and other cerebrovascular diseases specific diagnosis (4.3%). The average values of international normalized ratio (INR) (2.4±1.7) and warfarin dose (5.1±1.8mg) were within those recommended by therapeutic protocols. It was observed that 66.4% of patients received polypharmacy, which can raise the risk of DDI. In addition, 63.2% of patients had prescription(s) of drugs classified as D or X risk, with an average of 1.4 (±0.4) drugs per prescription, especially aspirin and amiodarone. Compared study group (n=429) versus control (n =2619), there was a statistically significant difference in mean age (years) (59.0±18.8 vs. 55.5±19.3; p<0.000), average number of medications/prescriptions (7.1±2.8 vs. 6.2±2.8; p<0.000), mean number of drugs with risk D and X DDI/prescription (1.4±1.3 vs. 1.0±1.0, p<0.000), serum albumin (g/dL) (3.4±0.6 vs. 3.7±0.6; p<0.000), aspartate aminotransferases (U/L) (60.7±200.6 vs. 41.5±84.5; p<0.005) and INR (4.9±3.4 vs. 2.1±0.7; p<0.000), factors that may have contributed to the occurrence of ADR in the study group. Conclusion. There was a high occurrence of possible DDI and ADR in patients treated with warfarin, which may compromise the effectiveness and safety of pharmacological treatment. Noteworthy is the high values of age, number of medications/prescriptions, prescription drugs classified as risk D or X, INR and aspartate aminotransferases, and lower values of serum albumin as potential risk factors for the occurrence of ADR.

The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in Endodontics and when associated with some risk factors, such as concomitant use of other drugs, may develop undesirable and possibly serious effects. This cross-sectional study evaluated, through data collecting on dental records, potential interactions among the most commonly prescribed NSAIDs and medications used by patients treated in the Integrated Clinical Dentistry of UFSM, from 2007 to 2011. The data were processed on the EpiData and the statistical analysis was performed with SPSS Software. For analysis of interactions between drugs two tertiary bibliographic source were used: the book Drug Interaction Facts and computerized tool Drugdex in the Micromedex. Potential drug interactions with NSAIDs occurred with 20.2% of the drugs related by patients. The most common consequences in this context were gastrointestinal bleeding, decrease antihypertensive effect and renal failure. In relation to gravity and documentation of interaction, there was a higher frequency of the important gravity and well-documented in the issue of pharmacological interaction. Hence, special attention must be given to the elderly and other patients using several drugs at the same time alongside with educational initiatives focused on a more safe prescription method should be taught in educational institutions. / Os anti-inflamatórios não esteroides (AINEs) são fármacos amplamente utilizados em Endodontia e, quando associadas a alguns fatores de risco, como uso concomitante de outros medicamentos, podem desenvolver efeitos indesejados e possivelmente graves. Esse estudo transversal avaliou, por meio de uma coleta de dados nos prontuários odontológicos, as potenciais interações entre os AINEs mais comumente prescritos e os medicamentos em uso pelos pacientes atendidos nas Clínicas Integradas do Curso de Odontologia da UFSM, no período de 2007 a 2011. Os dados foram codificados no Programa EpiData e a análise estatística foi realizada com o Software SPSS. Para análise das interações entre os fármacos foram utilizadas duas fontes bibliográficas terciárias: o livro Drug Interaction Facts e a ferramenta informatizada Drugdex do Micromedex. As potenciais interações medicamentosas com AINEs ocorreram em 20,2% dos medicamentos relatados pelos pacientes. As consequências mais frequentes nesse contexto foram sangramento gastrointestinal, diminuição do efeito anti-hipertensivo e insuficiência renal. Em relação à gravidade e a documentação da interação, observou-se maior frequência de gravidade importante e bem documentada no quesito interação farmacológica. Então, atenção especial deve ser dada a pacientes idosos e outros pacientes que utilizem diversos medicamentos de forma paralela e iniciativas educacionais focadas em um método de prescrição mais seguro devem ser lecionadas em instituições de ensino.

Magister Artium - MA / Dental caries is a multi-factorial disease that affects everyone irrespective of race, class or gender, however, the burden of the disease is often found in children from lower socio-economic backgrounds. The nature of the disease is such that it can be prevented. Various international studies on fluoride have shown a reduction in the prevalence of dental caries. By using geographical information systems, oral health data can be linked to the fluoride levels and further analysis could be done to identify areas at risk of dental caries as well as show patterns in the distribution of dental caries. The aim of this study was therefore to assess the effects of different levels of fluoride on the prevalence of dental caries in selected towns in the Northern Cape and Westen Cape. It also examined the application of Geographical Information Systems (GIS) to oral health data. / South Africa

Magister Public Health - MPH / Background: Namibia is one of the Southern African countries hardest hit by the HIV epidemic, with an estimated one out of every five people infected (MoHSS, 2004). Approximately 80,000 of the infected population currently require antiretroviral treatment (ART). In order to prevent the progression of the HIV infection to AIDS, patients are required to take antiretroviral medicines lifelong. This lifelong use exposes patients to toxicities of these medicines and the only available options of managing the toxicities of ARVs are to treat the toxicity or substitute or switch the offending medicines. Aim: The current study aimed to describe the extent and reasons for substituting and switching HAART at the Katutura Intermediate Hospital in Windhoek, Namibia. Methodology: A descriptive retrospective case series study, in which medical records were reviewed to determine the extent and reasons for substituting and switching HAART was conducted. Random sampling was used to draw a sample of 500 from 3477 adult HAART patients who commenced treatment between 1 January 2002 and 31 December 2006. A prepiloted data collection tool was used to collect the data. The following information was collected: baseline CD4 count, weight, initial ARVs, first and second ARV substitutions, ART switch and the reasons for substituting ARVs or switching ART during the indicated period. Epi Info version 6 was used to analyse frequencies, means and medians of all important variables in the data set. Results: The sample was made up of 500 HAART patients; 60% were females. The median age of the sample was 34 years (Inter-quartile range (IQR) 30 – 40) and the median CD4 cell count was 153 cells/mm3 (IQR 96 – 212) at initiation of therapy. The median time on treatment before first substitution was 28 months (IQR 24 – 34), whereas the median time before second substitution was 10 months (IQR 6 – 15) from the time of the first substitution. The median time before switching was 31 months (IQR 24 - 39). A total of 31% of the study subjects underwent a substitution once, whereas 1.8% underwent a second substitution. Only six (1.2%) patients switched to a second line treatment after the modification of the treatment. The most commonly recorded reason for the first substitution was toxicity (19%). As in other studies, stavudine (D4T), nevirapine (NVP) and efavirenz (EFV) were the ARVs associated with most of the recorded toxicities. High viral load (50%) was the most reported reason for switching. In almost half of the substitution cases the reasons for substitution were not stated, and in a third of the switch cases the reasons for switching were not stated. Conclusion: The rate of substitution at 31% was similar to that found in other resource poor settings, however, the rate of switching (1.2%) was much lower than was found in similar settings. The main reason stated for substituting antiretrovirals was “toxicity”. / South Africa

This study examines the effects of a low oxygen environment, in concert with fluctuating temperature and salinity conditions, on the nearshore depth distributions (0-1 m) and flood tide movements of juvenile chinook (Oncorhynchus tshawytscha) and chum (O. keta) salmon. Comparisons are made between an unpolluted and a sewage polluted estuarine intertidal flat in the Fraser River estuary, British Columbia, the polluted area being characterized by the regular occurrence of low dissolved oxygen levels. Results are based on 380 beach seine samples taken between April and June of 1984. In general, chum and chinook salmon of increasing length were captured in increasing depths, though this pattern was modified by seasonal changes in water temperature. Low dissolved oxygen conditions in deeper waters may have been responsible for the presence of larger, and often sluggishly swimming fish in higher oxygenated surface water layers or in shallow waters near the shore. In both areas, the risk of aerial predation was high. On a flood tide, the likelihood of capturing a chinook salmon was reduced as temperatures increased and oxygen levels decreased. A combination of avoidance behaviour and a regularity in the movement patterns of chinook onto the study area in the later stages of the flood tide may account for their rare occurrence in low oxygen concentrations (<6 mg/1) and high temperatures (>20 °C). Fish mortalities were most likely to occur on the ebb tide when fish were forced into waters of low oxygen content by the drainage patterns characteristic of the polluted study area. Though wide ranges in salinity were recorded on both tidal flats, this factor was not strongly correlated to Chinook distributions. However, significantly higher salinity levels in the unpolluted area may account for the greater numbers of chum salmon captured there. An understanding of the influence of estuarine water quality conditions on the distribution of juvenile salmonids may assist in the identification of significant sources of mortality in their early marine life. This knowledge is particularly important in the evaluation of water quality changes as caused by human activity. / Science, Faculty of / Zoology, Department of / Graduate

Dietary factors have been implicated in the etiology of colon cancer. The salient components of high-risk diets are thought to be high intakes of meat, especially beef, and fat, especially animal fat, and low intakes of fiber. Low-risk diets are thought to be high in fiber, and low in meat and animal fat. The present study examines the effects of short-term consumption of diets hypothesized to increase or decrease the risk for colon cancer on mutagenic activity of feces. Whether the fecal mutagens responsible for the mutagenic activity observed in the study are directly involved in the etiology of colon cancer is not known. However, most known mutagens are potentially carcinogenic, and fecal mutagenic activity may be an indicator of risk for colon cancer. Six healthy adult subjects consumed the following diets in sequence a baseline diet for one week, a low-risk lacto-ovo vegetarian, high fiber diet for two weeks, and a high-risk, high meat, low fiber diet for two weeks. Quantitative daily food intake records were kept, and daily bowel habits were recorded. Fecal samples were collected at the end of each diet period. Analyses were performed of the diets for food and nutrient intake, and of feces for percent dry weight and pH. Mutagenic activity of the fecal samples was assayed using the fluctuation test for mutagens. The subjects' habitual diets, although omnivorous, were found to closely resemble a low-risk diet pattern. Analysis of the vegetarian and high meat diets confirmed that the subjects had consumed foods which respectively represented the components of high-risk and low-risk diets. The overall fecal mutagenic activity obtained with samples on the high meat diet was higher than with the vegetarian or baseline diets using Salmonella typhimurium TA 98 and TA 100. The trend towards higher mutagenicity on the high meat diet over the vegetarian diet was consistent for all six subjects using TA 100, and for five of the six using TA 98. The vegetarian and baseline diets resulted in similar overall mutagenic activity. Analysis of the fecal sample parameters using the Kruskal-Wallis one-way analysis of variance showed no significant differences among fecal samples from the three diet periods with respect to wet weight, dry weight, percent dry weight, pH or number of daily bowel movements. However, a sign-test analysis showed a significant trend (p<0.05) towards fewer bowel movements on the high meat diet than on the vegetarian diet. There were significant differences among subjects for all of the fecal sample parameters (p<0.01 or p<0.001). Spearman rank correlations were significantly positive between mutagenic activities using bacterial strains Salmonella typhimurium TA 98 and TA 100 for the baseline diet (p<0.01) and the vegetarian diet (p<0.05). There were also significant positive correlations (p<0.001) between pH and fecal mutagenicity on the high meat' diet using tester strain TA 100, and between wet weight and dry weight. The results of this study indicate that the overall mutagenic activity of human feces can be increased over a period of two weeks by the consumption of a diet high in meat and low in fiber, which is considered to be a high-risk diet for colon cancer. / Land and Food Systems, Faculty of / Graduate

Mutagens in feces have been suggested to be an indicator for risk of colon cancer. Groups consuming vegetarian diets are known to have lower mortality from colon cancer. The purpose of this study was to assess mutagenic activity in feces of persons habitually consuming vegetarian or non-vegetarian diets and to try to identify dietary factors or other health habits which contributed to fecal mutagenicity. Eleven strict vegetarians, six ovo-lacto vegetarians and twelve non-vegetarians, all from the Greater Vancouver area, participated in this study. Data on certain demographic variables and health habits, as well as dietary intake (food frequency and food records), were taken. One fecal sample was collected from each subject for the study. Aqueous extracts of the feces were prepared and analyzed for mutagens using the fluctuation test with Salmonella typhimurium TA100 and TA98. Levels of mutagenicity on each organism were then statistically correlated with frequency of consumption of food groups, nutrient intake, demographic data and health habits. Ovo-lacto vegetarians and strict vegetarians, as groups, had significantly lower levels of fecal mutagens than non-vegetarians in the TA100 assay. With TA98, only the strict vegetarians had lower levels of mutagens compared to the non-vegetarians. The presence of several different mutagenic compounds was indicated. Significant negative correlations were found with mutagenicity on TA98 for all subjects with the following dietary variables: fruits and juices, fiber and iron. Similar negative correlations were found for total carbohydrate and Southgate fiber intakes and mutagenicity on TA100. Within the group of non-vegetarians, there were negative correlations with mutagenicity on TA98 and total protein and with mutagenicity on TA100 and calcium. With the demographic variables and health habits, no clear pattern emerged to indicate factors which would predict lowered mutagenicity for all subjects. It is concluded that vegetarians have lower levels of fecal mutagenicity and that several dietary factors are likely to contribute to this phenomenon. / Land and Food Systems, Faculty of / Graduate

OBJECTIVE: To review the evidence surrounding a potential association between liraglutide and pancreatitis. DATA SOURCES: A literature search was conducted in MEDLINE (1948-July 12, 2012) and EMBASE (1974-week 27, 2012) using the search terms pancreatitis, liraglutide, and glucagon-like peptide 1/adverse effects. Reference citations from identified publications were reviewed. The manufacturer was contacted and regulatory documents from the Food and Drug Administration website were reviewed for unpublished data related to cases of pancreatitis associated with liraglutide use. STUDY SELECTION AND DATA EXTRACTION: All identified sources that were published in English were considered for inclusion. DATA SYNTHESIS: Eleven cases of pancreatitis have been reported in patients taking liraglutide. Seven were from the LEAD (Liraglutide Effect and Action in Diabetes) studies, 1 was reported in the extension of a clinical trial, and 1 was in an unpublished obesity trial. Two were published postmarketing case reports. Nine of the cases reported were diagnosed as acute pancreatitis, while 2 were classified as chronic pancreatitis. The mean age of the patients was 57.5 years and mean body mass index was 33.92 kg/m2. Six of the 11 cases occurred in male patients. Nine of the patients were white and 1 was African American. In 7 of the cases, onset occurred at liraglutide doses at or above 1.8 mg daily. Common comorbidities included history of pancreatitis, cholelithiasis, and diabetes. One case was fatal. CONCLUSIONS: Pancreatitis is a potential complication with liraglutide therapy. Liraglutide should be used cautiously in patients at risk of pancreatitis (eg, alcohol abuse, history of pancreatitis, cholelithiasis).