Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2006. / Härtill 5 uppsatser. NB: Rätt ISBN från spikblad.

L’aluminium (Al) est le métal le plus abondant de notre environnement. Il est naturellement présent dans les sols, les roches, les minéraux, l’air, l’eau, et son utilisation pour la fabrication de produits de consommation courante n’a cessé d’augmenter de façon exponentielle dans les pays industrialisés. Durant les dernières décennies, la biodisponibilité de l’Al a fortement augmenté par l’activité humaine et les populations sont exposées quotidiennement à de multiples sources et doses d’Al, notamment par la voie orale. En se basant sur la description des effets toxiques et délétères de l’Al dans diverses pathologies ainsi que sur les doses d’Al ingérées, nous avons montré que l’Al pouvait participer à l’aggravation de l’inflammation intestinale, diminuer la cicatrisation muqueuse et le renouvellement cellulaire (Pineton de Chambrun et al., 2014).Dans le but de comprendre les mécanismes par lesquels l’Al perturbait l’épithélium intestinal, nous avons évalué la toxicité de l’Al sur la cellule épithéliale intestinale. Nous avons montré dans cette étude que l’Al diminuait la viabilité cellulaire, favorisait l’apoptose et perturbait le cycle cellulaire. L’Al avait également des effets pro-carcinogènes et pro-inflammatoires sur les cellules épithéliales intestinales. Ainsi, nous avons démontré que l’Al pouvait avoir des effets toxiques sur la muqueuse intestinale.Nous avons ensuite étudié les effets de l’Al sur la sensibilité viscérale chez le rongeur. Nous avons montré que l’ingestion d’une dose d’Al cohérente avec l’exposition humaine induisait une augmentation de la sensibilité viscérale chez le rat et la souris. Cette hypersensibilité induite par l’Al était persistante et exacerbée lors d’une nouvelle intoxication, indiquant ainsi qu’il n’y a pas de phénomène de tolérance. De plus, les femelles étaient plus affectées par l’hypersensibilité induite par l’Al que les mâles. Nous avons montré que les mécanismes impliquaient une augmentation de la perméabilité et étaient dépendants de la dégranulation des mastocytes et du récepteur aux protéases 2. Ces résultats sont pertinents avec la description des mécanismes observés dans la pathogénèse du syndrome de l’intestin irritable (SII). En effet, les malades présentent le plus souvent une hypersensibilité viscérale, une augmentation de la perméabilité intestinale, une altération du microbiote et une inflammation intestinale à bas grade. Les causes de cette maladie sont inconnues mais les facteurs environnementaux sont fortement suspectés. Ainsi, l’Al pourrait être un nouveau facteur de risque environnemental impliqué dans le développement du SII.En conclusion, ces résultats nous ont permis de démontrer la toxicité de l’Al sur le tube digestif et de mettre en avant un nouveau facteur de risque environnemental dans la physiopathologie des maladies intestinales telles que les maladies inflammatoires chroniques de l’intestin et le syndrome de l’intestin irritable. / Aluminium (Al) is the most abundant metal in our environment. Al naturally occurs in soils, rocks, minerals, air, water and its use in consumer products increase exponentially in industrialized countries. During last decades, human activities led to an increase in the bioavailability of Al and populations are exposed daily to multiple sources and doses of Al, including the oral route. Based on the description of toxic and deleterious effects of Al in various pathologies as well as ingested doses of Al, we showed that Al could participate in the exacerbation of intestinal inflammation, decrease mucosal healing and cell renewal (Pineton de Chambrun et al., 2014).In order to understand the mechanisms involved in the perturbations of the intestinal epithelium, Al toxicity was evaluated on intestinal epithelial cells. This study showed that Al decrease cell viability, promote apoptosis and disturb cell cycle. Al had also pro-tumorigenic and pro-inflammatory effects on intestinal epithelial cells. Thus, we demonstrated that Al could promote toxic effects on intestinal mucosa.Then, we evaluated the effects of Al on visceral sensitivity in rodents. We have demonstrated that currently ingested amounts of Al, in humans, induced in mice and rats a dose dependent increase of colorectal sensitivity. Al-induced hypersensitivity persists over time so that intoxication was arrested, and appears again when Al intoxication resumes, dismissing any tolerance phenomenon. Moreover, female gender was more affected by Al-induced hypersensitivity than male gender. Mechanisms involved an increased permeability and were dependent on mast cell degranulation and protease activated receptor 2. These results are relevant to the mechanisms observed in the pathogenesis of irritable bowel syndrome (IBS). Indeed, patients usually exhibit visceral hypersensitivity, increased permeability, impaired microbiota and low inflammation degree of the gastrointestinal tract. Causes of the disease remain unknown but environmental factors are strongly suspected to be involved in the pathogenesis. Thus, Al could be a new environmental risk factor involved in the development of IBS.In conclusion, these results demonstrate the toxicity of Al on the digestive tract and highlight a new environmental risk factor in the physiopathology of intestinal diseases such as inflammatory bowel diseases and irritable bowel syndrome.

M.A. / The overall objective of the global research project of which the present study is a part, is to create a greater awareness and understanding of the association between physiology and psychology, specifically with regard to IBS. Investigations are being conducted into the contribution of such factors as stress, anxiety, depression, somatization, psychopathology. early sexual abuse and physical abuse to the development and management of IBS. The present study aims to assess the incidence of co-morbid psychopathology in patients with IBS as compared to the general population. 1.3.2 Specific Aims. The aim of the present study is to compare the incidence of concurrent psychopathology in a sample of white, female patients, aged from 25-55 years and diagnosed to have IBS, with the incidence of psychopathology in a sample of white female non-IBS controls aged 25-55 years. Of initial concern will be whether the results of this study confirm the findings of the numerous research projects which attest to the high incidence of comorbid psychopathology in patients with IBS (Chaudhary & Truelove, 1962; Liss et al., 1973; Young et al., 1976), or add support to the limited evidence that disputes these claims (Talley, Kramlinger et al., 1993; Thornton, McIntyre et al., 1990). The study then aims to consider whether the variable of gender has a significant effect on the incidence of co-morbid psychopathology in patients with IBS. As will be discussed in Chapter 3, most of the studies do not differentiate between male and female subjects even though this may well prove to be an important determining factor. As mentioned in section 1.2.1, there is a dearth of research in South Africa into IBS and, more specifically, into the incidence of co-morbid psychopathology and IBS. By restricting participants in this study to those of the white race, the aim of this study is to initiate a process in which the incidence of co-morbid psychopathology in IBS patients of all races will be assessed and compared. In addition, the present study aims to assess whether age and level of education are significant variables in determining the incidence of co-morbid psychopathology in patients with IBS. Inter-group comparisons will be made between three groups of patients with IBS divided first according to age and then according to level of education. Finally, the present study aims to be more methodologically sound than certain of the earlier research projects as reported in the literature. As will become clear in Chapters 2 and 3, a common thread running through much of the literature is the concern that the validity of results may be questionable due to methodological flaws in the design of certain research projects. Small sample size has been a problem in some studies (Liss et al., 1973; Young et al., 1976) whilst in others, the absence of a control group has limited the relevance of data (Liss et al., 1973). Furthermore, a diversity of measuring instruments have been used in the past with little if any standardisation or control of specific variables being assessed. The measuring instrument used in this study, namely the Personality Assessment Inventory (PAI), allows for an accuracy and comprehensiveness of assessment not found in many previous studies (see Chapter 6, section 6.2.1.4). The PAI assesses psychopathological trends in personality functioning. The word "psychopathology" will be used in this study as substitute for the phrase "psychopathological trends in personality functioning".

The present study sought to determine whether a dietary and multi-element psychological treatment (DMPT) approach in combination with standard medical treatment would offer a more efficacious therapeutic package to irritable bowel syndrome (IBS) patients than would standard medical treatment (SMT) employed alone. The DMPT group (N = 19) received a stress management training package for a 2 week period consisting of relaxation training, imagery, and bowel sound biofeedback training via a stethoscope, in addition to instructions to increase their daily consumption of dietary fiber. They also were to continue the implementation of whatever standard medical treatment they were currently receiving, be it a bulking agent, or anti-anxiety, anti-cholinergic, or anti-depressant medications, etc. The SMT group (N = 19) simply received whatever conventional medical treatment they had been prescribed.

Background - Irritable bowel syndrome (IBS) is a poorly understood functional gastrointestinal disorder and is a major cause of abdominal discomfort and gut dysfunction. IBS symptoms encompass abdominal pain, bloating, flatulence and irregular bowel movements such as constipation, diarrhoea and alternating bowels, bloating, flatulence and irregular bowel movements. Physiological studies have shown that manipulation of the intestinal microbiota by antibiotics, prebiotics or probiotics can affect intestinal functions in the pathogenesis of IBS. The probiotic concept suggests that supplementation of the intestinal microbiota with the right type and number of live microorganisms can improve gut microbiota composition and promote health in IBS sufferers. Aim - The aim of the main clinical trial is to determine whether ingestion of fermented milk containing Bifidobacterium animalis DN-173010 is associated with improved defecation frequency, stool consistency and quality of life in black South African females with constipation-predominant IBS (IBS-C). Methods - A pilot and process evaluation approach was employed during the current study to examine and understand the feasibility of implementing the study and to explore the facilitating implementation of the main clinical trial. Twenty black female participants, aged 18-60, with IBS-C were recruited from the practices of gastroenterologists, specialist physicians and medical doctors in Soweto. Participants fulfilling the Rome III criteria for IBS-C and inclusion criteria were randomized into two groups to participate in a 4-week, double blind, placebo controlled study. The placebo group received unflavoured sweetened, white base yoghurt and the intervention group received similar yoghurt with the probiotic, Bifidobacterium animalis DN-173010 [>3,4X10⁷ CFU/g]. Participants were required to record their bowel movements daily and IBS symptoms weekly in questionnaires during the four-week study period. Quality of life was assessed at baseline and at the end of the treatment period. Participants visited the study unit weekly to collect the placebo or probiotic study products and return the completed questionnaires during the study period. Results - Seventeen participants completed the study (eight intervention and nine placebo). There were not significant differences in IBS symptoms between the two groups, but differences were observed overtime within groups. The severity of abdominal pain score within both groups was statistically significant (p=0.004), and the number of days with pain was also statistically significant (p=0.00001). The frequency of normal stools reported was statistically significant different compared to all the other stool types (constipation and loose stools) throughout the four-week study period in both the intervention and placebo group. There was no significant difference in the quality of life between the intervention group compared to the placebo group. Conclusion - Process evaluation allows for the monitoring of a programme and corrections of problems as they occur. The intervention is feasible to implement, acceptable and safe to participants. The study indicates that consumption of the probiotic Bifidobacterium animalis DN-173010 for four weeks is not superior to the placebo in relieving IBS symptoms. / MSc (Dietetics), North-West University, Potchefstroom Campus, 2014

Background - Irritable bowel syndrome (IBS) is a poorly understood functional gastrointestinal disorder and is a major cause of abdominal discomfort and gut dysfunction. IBS symptoms encompass abdominal pain, bloating, flatulence and irregular bowel movements such as constipation, diarrhoea and alternating bowels, bloating, flatulence and irregular bowel movements. Physiological studies have shown that manipulation of the intestinal microbiota by antibiotics, prebiotics or probiotics can affect intestinal functions in the pathogenesis of IBS. The probiotic concept suggests that supplementation of the intestinal microbiota with the right type and number of live microorganisms can improve gut microbiota composition and promote health in IBS sufferers. Aim - The aim of the main clinical trial is to determine whether ingestion of fermented milk containing Bifidobacterium animalis DN-173010 is associated with improved defecation frequency, stool consistency and quality of life in black South African females with constipation-predominant IBS (IBS-C). Methods - A pilot and process evaluation approach was employed during the current study to examine and understand the feasibility of implementing the study and to explore the facilitating implementation of the main clinical trial. Twenty black female participants, aged 18-60, with IBS-C were recruited from the practices of gastroenterologists, specialist physicians and medical doctors in Soweto. Participants fulfilling the Rome III criteria for IBS-C and inclusion criteria were randomized into two groups to participate in a 4-week, double blind, placebo controlled study. The placebo group received unflavoured sweetened, white base yoghurt and the intervention group received similar yoghurt with the probiotic, Bifidobacterium animalis DN-173010 [>3,4X10⁷ CFU/g]. Participants were required to record their bowel movements daily and IBS symptoms weekly in questionnaires during the four-week study period. Quality of life was assessed at baseline and at the end of the treatment period. Participants visited the study unit weekly to collect the placebo or probiotic study products and return the completed questionnaires during the study period. Results - Seventeen participants completed the study (eight intervention and nine placebo). There were not significant differences in IBS symptoms between the two groups, but differences were observed overtime within groups. The severity of abdominal pain score within both groups was statistically significant (p=0.004), and the number of days with pain was also statistically significant (p=0.00001). The frequency of normal stools reported was statistically significant different compared to all the other stool types (constipation and loose stools) throughout the four-week study period in both the intervention and placebo group. There was no significant difference in the quality of life between the intervention group compared to the placebo group. Conclusion - Process evaluation allows for the monitoring of a programme and corrections of problems as they occur. The intervention is feasible to implement, acceptable and safe to participants. The study indicates that consumption of the probiotic Bifidobacterium animalis DN-173010 for four weeks is not superior to the placebo in relieving IBS symptoms. / MSc (Dietetics), North-West University, Potchefstroom Campus, 2014

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background: Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder. GI symptoms and impaired quality of life affect between 10-20% of all adults, corresponding to about 25-50% of all patients who visit a gastroenterologist’s clinic. In recent years, several novel mechanisms of IBS that likely relate to previously established theories have been identified. Inflammation, postinfectious low-grade inflammation, immunological and genetic predisposition along with altered microbiota are critical in IBS development, while several dietary factors may also play a role in this syndrome. However, none of these factors accounts for the full repertoire of IBS symptoms, and the pathophysiology of this condition is not fully understood. The overarching aim of this study was to investigate the nutrient intakes, GI microbiota and the effect of Lactobacillus plantarum (L.plantarum) 299v in IBS patients. Sub-aims: 1) Update healthcare professionals on current probiotic information and provide an overview of probiotic treatment approaches, with special emphasis on IBS, 2) conduct a well designed randomised, double blind, placebo-controlled trial (RCT) with L. plantarum 299v as part of an intervention and establish whether a course of probiotics may alleviate undesirable symptoms of IBS and improve quality of life, 3) assess nutrient intake in patients with irritable bowel syndrome (IBS) compared to dietary recommendations, 4) validate and assess the reproducibility of food records and 5) identify possible nutrient risk components for establishing GI microbiota involved in IBS and as part of an intervention, determine whether a course of probiotics may alter stool microbiota. Results: 1) A review article published by the author provides an overview of current probiotic treatment options to health care professionals and indicates certain probiotics are a promising therapeutic treatment option for management of IBS symtpoms, 2) the effects of the single strain probiotic, L. plantarum 299v, supplementation was evaluated in a RCT. Compared to placebo, the probiotic supplementation showed no significant reduction in GI symptom severity scores, particularly abdominal pain relief. Quality of life was also not improved in the treatment versus control group. Both the treatment and placebo groups improved significantly over the trial period, indicating a large placebo effect, 3) nutrient intakes of the IBS patients compared to current dietary reference recommendations indicates that this group of patients are at risk for nutrient inadequacies in key macro and micronutrients, 4) the validity and reliability of the dietary data showed good reliability but poor validity as measured by plasma fatty acids and 5) the GI microbiota composition in the phenotypically different diarrhoea-predominant IBS (D-IBS) vs. constipation-predominant IBS (C-IBS) showed that D-IBS patients had significantly lower counts of Lactobacillus plantarum compared to C-IBS patients. The probiotic had no significant effects on the GI microbiota as measured by quantitative polymerase chain reaction (qPCR). It was found that nutrient intakes had a significant impact on the microbiota. Lower fibre intakes were associated with higher Bacteroides spp., lower Bifidobacteria bifidum and Lactobacillus plantarum counts in both IBS groups. Conclusion: Taken together, L.plantarum 299v did not alleviate the GI symptoms of IBS, nor was it associated with significant changes in the GI microbiota. IBS patients may be at risk of key nutrient inadequacies. The influence of nutrient intakes on the GI microbiota provides an attractive explanation as a potential pathophysiological factor for IBS. / AFRIKAANSE OPSOMMING: Agtergrond: Prikkelbare derm-sindroom (PDS) is ‘n algemene gastro-intestinale (GI) stoornis. GI simptome affekteer die lewenskwaliteit van 10-20% van alle volwassenes. Dit stem ooreen met ongeveer 25-50% van alle pasiënte wat ‘n gastroënteroloog konsulteer. Verskeie oorspronklike meganismes vir die ontwikkeling van PDS is onlangs identifiseer. Inflammasie, post-infektiewe lae-graadse inflammasie, immunologiese en genetiese vatbaarheid tesame met veranderde mikrobiota is krities vir die ontwikkeling van PDS. Sekere dieetfaktore mag ook bydraend wees tot hierdie sindroom. Geen van hierdie faktore is egter verantwoordelik vir die volle spektrum van PDS simptome nie en die patofisiologie van die toestand word ook nog nie ten volle verstaan nie. Die oorkoepelende doel van hierdie studie is om nutriëntinname, GI mikrobiota en die uitwerking van L.plantarum 299v in PDS pasiënte bepaal. Sub-doelwitte: 1) Om gesondheidswerkers in te lig aangaande die nuutste inligting oor probiotika en om ‘n oorsig van probiotika behandelingsopsies te verskaf, met spesiale klem op PDS, 2) om ‘n goed beplande ewekansige, dubbel-blinde, plasebo-beheerde kliniese studie met L.plantarum 299v as deel van die intervensie uit te voer om sodoende te bepaal of ‘n kursus probiotika ongewensde simptome van PDS kan verbeter en lewenskwaliteit sodoende verhoog, 3) om nutriëntinname in pasiënte met PDS te bepaal vergeleke met dieet aanbevelings, 4) om die geldigheid en herhaalbaarheid van voedselrekords te bepaal en 5) om moontlike nutriënt risikokomponente vir die ontwikkeling van GI mikrobiota betrokke in PDS te identifiseer en om as deel van ‘n intervensie te bepaal of ‘n kursus probiotika stoelgang mikrobiota patrone verander. Resultate: 1) ‘n Oorsigartikel gepubliseer deur die kandidaat dui probiotika aan as ‘n belowende terapeutiese opsie in die behandeling van PDS simptome, 2) die effek van ‘n enkelstam probiotikum, L.plantarum 299v, is evalueer deur ‘n ewekansige, dubbel-blinde, plasebo-beheerde kliniese studie. Vergeleke met die plasebo, het probiotiese aanvulling geen betekenisvolle vermindering in die GI simptome in PDS pasiënte tot gevolg gehad nie. Lewenskwaliteit het ook nie verbeter in die behandelde versus die kontrole groep nie. Beide die behandelde en plasebo groepe het aansienlik verbeter oor die studietydperk, wat ‘n groot plasebo effek aandui, 3) nutriëntinname van die PDS groep vergeleke met huidige dieetaanbevelings, dui daarop dat hierdie groep pasiënte ‘n risiko het vir die ontwikkeling van kern nutriënttekorte (makro- en mikronutriënte), 4) die geldigheid en betroubaarheid van die dieetdata dui op goeie betroubaarheid, maar swak geldigheid soos bepaal deur plasma vetsure en 5) die dermkanaal mikrobiotiese samestelling in die verskillende fenotipes, diarree-oorheersende PDS (D-PDS) vs. konstipasie-oorheersende PDS (K-PDS) dui daarop dat D-PDS pasiënte aansienlike minder Lactobacillus plantarum gehad het vergeleke met K-PDS pasiënte. Die probiotikum het geen beduidende uitwerking op die oorheersende mikrobiota gehad nie, soos gemeet deur kwantitatiewe polimerase kettingreaksie (kPKR). Daar is gevind dat dieet ‘n beduidende impak op die mikrobiota gehad het. Daar is ‘n verband tussen laer vesel inname en hoёr Bacteroides spp. en laer Bifidobacteria bididum en Lactobacillus plantarum tellings gevind in beide PDS groepe. Gevolgtrekking: Die L.plantarum 299v enkelstam probiotikum het nie die gastrointestinale simptome van PDS pasiënte verlig nie en daar is ook geen beduidende veranderinge in die mikrobiota gevind nie. PDS pasiënte mag ‘n verhoogde risiko toon vir kern nutriënttekorte. Die invloed van nutriëntinname op GI mikrobiota verskaf ‘n belowende verduideliking as ‘n potensiële patofisiologiese faktor in PDS.

El síndrome de intestino irritable (SII) es una entidad cuya prevalencia varía según el método utilizado para diagnosticarlo. Objetivo: determinar la prevalencia del SII en Chiclayo-Perú durante el año 2011. Materiales y métodos: población diaria: personas entre 18 y 60 años; diseño de estudio: descriptivo transversal. Tamaño muestral: 195 personas, muestreo aleatorio, estratificado multietápico. Se entrevistó casa a casa usando una ficha de recolección de datos basada en los criterios de Roma III. Se utilizó estadística descriptiva y análisis bivariado para medir asociación entre SII y variables epidemiológicas. Resultados: 200 personas fueron entrevistadas, 76 varones (38%) y 124 mujeres (62%). La media de edad fue 38,8 años ± 12,7. La prevalencia de SII fue de 15%; siendo la localización del dolor más frecuente el mesogastrio (26,7%); predominando las heces “pastosas” (30%) y la “diarrea” (36,7%). 20 personas con SII (66,7%) trabajaban y/o estudiaban. No hubo asociación entre SII y sexo femenino ni “ocupación” (Odds de prevalencia: 1,51; IC95%: 0,31-3,99 y 1,23; IC95%: 0,51-3,15 respectivamente). Conclusiones: la prevalencia de SII en Chiclayo es elevada, más frecuente en mujeres y quienes laboran o estudian; la diarrea, la consistencia pastosa de las heces y el dolor mesogástrico fueron las manifestaciones clínicas más frecuentes. / Tesis

Irritable bowel syndrome (IBS) är en sjukdom som leder till en funktionell motorisk störning i mag-tarmkanalen och symtom som förstoppning, diarré, gasbesvär, buksmärta och uppspänd buk är vanligt förekommande. Symtomen leder ofta till stress, depression, ångest vilket kan medföra ett begränsat vardagsliv. Individens livskvalitet påverkas av vad symtomen orsakar för individen i vardagslivet vilket kan leda till lidande. Syftet med litteraturstudien var att granska och sammanställa vårdvetenskaplig forskning som belyser patienters upplevelser av att leva med IBS. Metoden är en litteraturstudie utifrån Fribergs modell. Sex kvalitativa artiklar och tre kvantitativa artiklar har analyserats. Resultatet visade att kroppen var opålitlig då sjukdomen orsakade fysiska symtom och gav oönskade symtom som gasbesvär, smärta i buken, diarré, förstoppning och uppspändhet. Patienter upplevde begränsningar i vardagen i form av symtom som ökade gasbesvär, uppspändhet, diarré. Patienter hade ständigt uppsikt efter toaletter då de gick hemifrån vilket ofta skapade en ökad oro. Symtom som gasbildningar och diarré innebar att patienter ofta behövde gå på toaletten vilket var besvärligt i samband med möte, arbete, skola. Detta upplevde patienter vara skamligt. Sjukdomen bidrog i längden till ökad stress, ångest, depression och isolering hos patienterna. Detta har orsakat minskat förtroende till vården, patienterna upplevde sig missförstådda och välbefinnandet minskade. Strategier och planering bidrog till bekräftelse, medvetenhet, kunskap och förståelse. Patienter upplevde sig ha bättre koll på symtomen och kunde agera tills värken släppte. Sjuksköterskan har en viktig roll där hen kan hjälpa patienten att känna välbefinnande, hopp, livslust och ökad självkänsla genom bekräftelse av att bli sedd och hörd samt ge nyttig kunskap för att patienter ska kunna hantera sin sjukdom med bra planering och strategier.