Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) which can be defined as chronic, relapsing visceral pain with bloating associated with change in bowel habit. It affects up to 10-15% of the adult population in the UK and is more common in females. The cost of IBS in terms of health care utilisation is substantial, exceeding £45.6 million per year in the UK alone, yet its pathophysiology is incompletely understood. Visceral pain is the main and most difficult symptom to manage in IBS and many IBS female sufferers compare it to labour pain in its severity. Modulating visceral pain in healthy volunteers and IBS patients is therefore an important research area. Non-invasive magnetic stimulation may play a crucial role in this respect. Aim:The aim of this study is to ascertain whether non-invasive repetitive magnetic stimulation applied to the motor cortex and/or lumbosacrum can modulate gastrointestinal pain originating from the anorectum. Methods:Participants: 16 healthy volunteers and 10 IBS patients aged 18 and above were included in the study.Questionnaires: Healthy volunteers and IBS patients were asked to complete anxiety and depression questionnaire and IBS patients were requested to fill in an IBS severity questionnaire.Motor measurements in healthy subjects: Single-pulse lumbosacral magnetic stimulation (LSMS) was applied to the lumbosacral area for the anal sphincter where the largest motor evoked potential (MEP) amplitude response was detected. Single-pulse transcranial magnetic stimulation (TMS) was then performed at the pre-determined resting motor thresholds (RMT) for the anal sphincter and the hand.Sensory measurements in healthy subjects and IBS patients: Electrical stimulation was used to assess the changes in sensory and pain thresholds in the anorectal area. The subjects were asked to score the pain intensity using five-point categorical rating scales. In addition they were asked to describe the pain experienced using a shortened form of the McGill Pain Questionnaire. Intervention: Healthy volunteers received 6 paradigms of magnetic stimulation in a randomised order i.e. 3 repetitive LSMSs (1 Hz, 10 Hz and sham) and 3 repetitive TMSs (1 Hz, 10 Hz and sham) to investigate their modulatory effects on visceral sensitivity and to determine which of these interventions is most effective. The most effective active interventions (1 Hz rLSMS and 10 Hz rTMS) together with one sham were then trialled in a randomised fashion on IBS patients.Post intervention: Motor excitabilities were repeated at 30 min after each intervention. The assessment of sensory and pain thresholds at anal sphincter and rectum were done immediately, 30 and 60 min after each intervention. Results:Application of 1 Hz rLSMS led to alterations of anal sphincter motor excitabilities and resulted in a significant increase in the amplitude of lumbosacal-anal motor evoked potentials (MEPs) in healthy volunteers recorded at 30 min post intervention. In healthy volunteers, 1 Hz rLSMS and 10 Hz rTMS caused a significant increase in the rectal pain thresholds experienced immediately, 30 and 60 min after each intervention. 10 Hz rLSMS and 1 Hz rTMS only led to a significant rise in rectal pain thresholds immediately after their application. Furthermore, there was a significant increase in the rectal pain thresholds immediately, 30 and 60 min following 1 Hz rLSMS and 10 Hz rTMS in IBS patients. Conclusion:The application of magnetic stimulation to the cortical and lumbosacral areas to modulate visceral pain is a new concept, which reduced rectal sensitivity to painful stimuli and offers a much needed new approach in the management of abdominal pain in patients with IBS.

Background: Irritable bowel syndrome (IBS) is an extremely common condition affecting approximately 10-15% of the population. Lower abdominal pain is a common feature and, if the patient also has gynaecological symptoms such as heavy periods, they may be referred to a gynaecologist especially when the bowel symptoms are relatively mild. In this setting a laparoscopy is often undertaken and endometriosis commonly identified as this condition affects up to 10% of women. Consequently pain is frequently attributed to the endometriosis even when it is relatively mild. However it is a common observation amongst gynaecologists that women with mild endometriosis often have severe symptoms which do not seem to respond well to treatment. This raises the possibility that their pain may not actually be due to endometriosis or is being amplified by the visceral hypersensitivity which is a characteristic feature of irritable bowel syndrome.Methods: 20 patients with minimal-mild endometriosis, 20 with moderate-severe endometriosis, 20 healthy volunteers (HV) who have had laparoscopy for sterilisation, 20 IBS patients and 20 patients with pain who were found to have a normal pelvis (on laparoscopy) were studied. Gastrointestinal, gynaecological, and noncolonic symptoms were recorded as well as demography, quality of life and psychological status. Visceral sensitivity was assessed in all patients and abdominal distension was studied in a sub group of 26 endometriosis patients and 20 IBS patients.Results: 20 (100%) of IBS patients, 13 (65%) of minimal-mild endometriosis patients, 11 (55%) of moderate-severe endometriosis patients, 17 (85%) of laparoscopic negative pain patients and no healthy volunteers fulfilled ROME III criteria for IBS. Patients with endometriosis and IBS had similar levels of visceral sensitivity which were significantly lower than that observed in controls (p=0·002, p<0·001).In particular, both minimal-mild and moderate-severe endometriosis patients had significantly lower (mean-95% CI) pain thresholds in mmHg 28.1(24.5, 31.6) and 28.8(24.9, 32.6) respectively compared with controls 39·5 (36·0, 43·0) p=0.001and p=0.002. However, with few exceptions, there were no distinguishing features between patients in terms of demography, symptomatology and distension.Conclusion: Clinically, it is very difficult to distinguish between endometriosis and IBS. However, visceral hypersensitivity appears to be a major component of endometriosis and may explain the problem of excessive pain especially in patients with mild disease offering a potential new target for treatment

Un des enjeux relatifs à la durabilité des élevages équins est d’accroître la part de l’herbe dans l’alimentation sans compromettre les performances animales. Les chevaux à forts besoins, comme la jument en lactation, sont en effet couramment complémentés au pâturage alors même que l’impact de la complémentation sur leur ingestion et leurs performances n’est pas connu. Un second enjeu est d’identifier des solutions alternatives aux anthelminthiques pour gérer leurs parasites gastro-intestinaux en évitant le développement de résistances et le rejet de molécules toxiques dans l’environnement. Notre première expérimentation a montré qu’en conditions de pâturage non limitantes, la complémentation énergétique n’était pas indispensable. Les juments en lactation non complémentées ont accru leurs quantités ingérées journalières jusqu’à 28 g MS.kg PV -1 .j -1 , un niveau d’ingestion permettant de satisfaire leurs besoins énergétiques. La croissance des poulains et leur conformation n’ont donc pas été affectées par l’absence de complémentation énergétique, celle-ci n’ayant par ailleurs pas permis aux juments de mieux réguler leur charge parasitaire. La deuxième expérimentation, a permis de préciser le seuil en deçà duquel la complémentation énergétique devient nécessaire pour couvrir les besoins de la jument en lactation. Pour un pâturage au fil de repousses végétatives celui-ci a été estimé à 66 g MS.kg PV-1.j -1 , ce qui correspond à une hauteur de sortie de parcelle à 5,4 cm au stick, soit 4,5 cm à l’herbomètre à plateau. Enfin, la troisième expérimentation en box a permis de mettre en évidence l’efficacité d’une distribution de courte durée de sainfoin, une légumineuse riche en tanins condensés, pour réduire le développement des œufs de nématodes en larves infestantes ; une complémentation azotée « simple » s’est en revanche révélée inefficace. L’ensemble de ces résultats ouvre des perspectives pour optimiser la conduite alimentaire de la jument en lactation au pâturage. / Sustainable horse breeding requires increasing the proportion of herbage in horse diet without affecting animal performance. Horses with high requirements such as lactating mares are commonly supplemented at pasture, while the consequences of energy supplementation on intake and performance remain unknown. Another priority is to identify alternatives to chemical anthelmintic for gastro-intestinal parasite management in order to limit the spread of antibiotic resistance and the dumping of pharmaceutical residues into the environment. A first experiment showed that supplementing lactating mares at pasture should not be systematic because, under non-limiting conditions, their adaptive capacities enabled them to increase herbage intake up to 28 g DM.kg LW -1 .d -1 and ensure foal growth. In addition, energy supplementation did not allow mares to better regulate their parasite burden. A second experiment allowed us to precise the herbage allowance threshold below which energy supplementation is required. Under strip-grazing conditions it was estimated at 66 g DM.kg LW -1 .d -1 , which corresponds to a post-grazing height of 5.4 cm using sward stick. A third experiment has revealed the potential of secondary metabolites of sainfoin to reduce the nematode larval development, while no effect was observed with a short-term protein supplementation. These original results have practical implications for a better management of lactating saddle mares at pasture.

Les nématodes gastro-intestinaux sont des parasites de la caillette des petits ruminants qui posent des contraintes majeures pour l’élevage de ces animaux dans le monde. Récemment leur impact économique a augmenté notamment à cause de l’apparition de nématodes résistants aux anthelminthiques. La sélection génétique pourrait être une stratégie complémentaire des traitements chimiques. Dans cette thèse, nous avons exploré la variabilité génétique disponible qui permettrait une sélection sur la résistance aux nématodes. Les résultats obtenus en termes d’héritabilités, corrélations génétiques et QTLs, suggèrent que la variation génétique des populations étudiées pourrait satisfaire les requis d’un objectif de sélection permettant à la fois d’améliorer la résistance aux nématodes et la croissance des animaux. En outre, l’identification de loci SNP associés à la variation observée sur les caractères de résistance aux nématodes pourrait nous permettre d’améliorer la réponse à la sélection. / Abomasal nematodes are a major constraint to small ruminants industry worldwide. Recently their economic impact has increased due to the recrudescence of anthelmintic resistance among many parasite populations. Genetic selection might be a valid strategy for enhancing the efficacy of anthelmintics. We explored the genetic variability, in both sheep and goat, possibly available for a breeding plan featuring parasite resistance as its breeding goal. The results obtained in terms of heritabilities, genetic correlations and QTLs, suggest that the variation in the genetic pool of the population under study might comply with the requirements of a breeding goal including both parasite resistance and production traits. Furthermore, marker assisted selection could be a feasible option to enhance the selection response.

Orientadores: Jaime Amaya-Farfan, Fernanda de Pace / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-27T02:35:33Z (GMT). No. of bitstreams: 1 Monteiro_NaiceEleidianeSantana_M.pdf: 1835989 bytes, checksum: ec62cf398adabcdca614249ae2d4692b (MD5) Previous issue date: 2015 / Resumo: Caracterizada como um dos mais importantes problemas que a saúde pública enfrenta atualmente no Brasil e no mundo, a obesidade está associada a um quadro de inflamação subclínica, que predispõe à resistência à insulina e ao desenvolvimento de diabetes mellitus, além de representar fator etiológico para diversas outras doenças crônicas não transmissíveis. Sabendo da importância que os alimentos com propriedades bioativas podem ter no tratamento da obesidade é que a utilização das proteínas do soro do leite na dieta vem sendo alvo de diversos estudos, devido aos benefícios que podem trazer à saúde humana. Dentre as propriedades da whey protein, citam-se a capacidade de regular a função imune, atuar como agente antimicrobiano, estimular a síntese de proteína muscular, suprimir o apetite e atuar na redução da gordura corporal, além das propriedades de aumentar a expressão gênica de proteínas anti-estresse (HSPs) e de ativar o transportador de glicose GLUT4, ambas descobertas pelo nosso grupo da FEA. O presente estudo teve como objetivo investigar o impacto que as proteínas do soro do leite, seja na sua forma íntegra ou na forma hidrolisada, possam exercer sobre a homeostase e a proteção do organismo de camundongos, contra os danos causados por uma dieta hiperlipídica. Para alcançar este objetivo, 34 camundongos C57BL/6 recém-desmamados foram divididos em quatro grupos de forma aleatória e alimentados com as seguintes dietas: grupo controle normolipídico (AIN93-G), grupo controle hiperlipídico (HFCAS), grupo hiperlipídico com substituição da caseína pela proteína do soro de leite concentrada (HFWPC), e grupo hiperlipídico, com adição da proteína do soro do leite hidrolisada (HFWPH), por 9 semanas. Os camundongos foram acompanhados quanto ao consumo alimentar e ganho de peso por meio de avaliação poderal em dias alternados, parâmetros bioquímicos e de endotoxemia avaliados por técnicas convencionais, biomarcadores inflamatórios analisados por western blot, além da avaliação do perfil histopatológico do fígado e do estudo metagenômico da microbiota intestinal. Os resultados demonstraram que alimentação com a formulação contendo whey protein, em ambas as formas, por 9 semanas, não diminuiu ganho de peso em comparação aos demais tratamentos, mas foi efetiva em reverter a disbiose causada pela dieta gordurosa, reduzir o processo inflamatório para níveis indistinguíveis do controle, em atenuar a infiltração gordurosa no tecido hepático, além de modular a microbiota intestinal. A caseína não mostrou tais propriedades / Abstract: Recognized as one of the most important issues currently facing public health in Brazil and in the world, obesity is associated to a subclinical inflammation framework, which predisposes to insulin resistance and the development of diabetes mellitus, in addition to representing an etiological factor for several other chronic diseases. Owing to the bioactive properties that the milk whey proteins may have on human health, such as the ability to regulate immune function, act as an antimicrobial agent, stimulate protein synthesis, suppress appetite thus helping to reduce body fat, besides the two newly discovered functions from our laboratory regarding the up-regulation of protective HSPs and activation of the glucose transporter 4 (GLUT4), it is thought that these proteins may also have anti-inflammatory action and, therefore, this study was designed to investigate the impact that whey protein, either in its normal form or in the hydrolyzed form, may exert on homeostasis protecting the mouse from the adverse effects of a high-fat diet. To accomplish this, 34 C57BL/6 male mice were randomly divided into four groups that received the following diets for 9 weeks: Normolipidic control (AIN93-G), Hyperlipidic control (HFCAS), Hyperlipidic with whey protein concentrate instead of casein (HFWPC) and a Hyperlipidic group with hydrolyzed whey protein (HFWPH) as the only source of protein. Diet intake and weight gain were monitored and recorded every other day. Biochemical parameters and endotoxemia were evaluated using commercial kits, and inflammatory biomarkers were analyzed by western blotting, besides the evaluation of histopathological liver profile and metagenomic study of the intestinal microbiota. The results showed that feeding the formulation contendowheyprotein, in both its forms, for 9 weeks, not decreased weight gain compared to the other treatments, but was effective in reversing dysbiosis caused by high-fat diet, reduce inflammation to levels indistinguishable control and mitigate the fatty infiltration of the casein hepático, in addition to modulate the gut microbiota. Casein did not show such properties / Mestrado / Nutrição Experimental e de Alimentos / Mestra em Alimentos e Nutrição

Em função de sua disponibilidade no mercado e qualidade nutricional, derivados da soja são importantes fontes de proteína na alimentação animal. Apresentam perfil de aminoácidos semelhante ao de fontes animais, o que estimula seu uso como potencial substituto da farinha de peixe nas rações para aquicultura. No entanto, são deficientes em aminoácidos sulfurados e apresentam fatores antinutricionais que prejudicam o crescimento de peixes. O processamento da soja permite obter produtos mais refinados e altamente digestíveis, como concentrados proteicos (CPS), que têm elevado teor proteico e baixa quantidade de fatores antinutricionais, extraídos no processo de fabricação. Neste contexto, foi determinado o Coeficiente de Digestibilidade Aparente (CDA) do CPS em dietas para juvenis de duas espécies de Characidae autóctones: pacu (Piaractus mesopotamicus) e dourado (Salminus brasiliensis). Também foram avaliados os efeitos do uso deste ingrediente em níveis crescentes de substituição da farinha de peixe na dieta (ensaios com seis tratamentos e quatro repetições), com o objetivo de determinar o nível seguro de substituição sem prejudicar o ganho de peso. O pacu apresentou CDA para proteína (95,33 %) e energia (84,29 %) mais altos que o dourado (CDAproteína = 82,6 %; CDAenergia = 66,6 %), indicando maior plasticidade da espécie para o aproveitamento de fontes vegetais. Baseado em ensaios de desempenho, nas dietas para pacu foi possível substituir até 78,05 % da farinha de peixe das dietas experimentais, enquanto que para dourados, até 37,2%. Acima destes níveis, houve redução no crescimento. A substituição crescente da farinha de peixe pelo CPS exerceu efeito regulatório sobre a atividade de enzimas pancreáticas nos primeiros segmentos do intestino das duas espécies, mensurada através da atividade da protease inespecífica, lipase inespecífica e &alpha;-amilase. Também promoveu redução na altura das dobras intestinais quando a substituição foi total, detectada através da morfometria da parede intestinal do intestino anterior. Estes efeitos podem ser consequência da ação conjunta de fatores antinutricionais da soja, principalmente inibidores de enzimas, potencializados quando a farinha de peixe foi totalmente substituída pelo CPS; e da habilidade com a qual cada espécie digere / absorve os nutrientes. Com base nos resultados obtidos, foi possível concluir que o CPS pode ser utilizado em substituições parciais da farinha de peixe em dietas para peixes onívoros e carnívoros. / Because of market availability and nutritional quality, soybean and its by-products are important sources of protein for the animal feed industry. The amino acid profile of soy products is similar to that of animal sources, encouraging their use as surrogate protein source to fishmeal (FM) in aquafeeds. However, soy products and by-products are deficient in sulfur amino acids and contain anti-nutritional factors that hamper fish growth. Secondary processing of soybean meals yield more refined and highly digestible protein ingredients such as the soy protein concentrate (SPC), which have higher protein contents and lower concentration of anti-nutritional factors, partially extracted or inactivated during the manufacturing process. In such a context, this work determined SPC\'s Apparent Digestibility Coefficient (ADC) in diets for two juveniles neotropical, native Characins species: pacu (Piaractus mesopotamicus), and dourado (Salminus brasiliensis), and also studied the effects of replacing graded levels of FM by SPC (six treatment levels and four repetions) in the aim to determine the optimum substitution level for better growth. Pacu presented higher ADC for protein (95,33 %) and energy (84,29 %) than dourado (ADCprotein = 82,6 %; ADCenergy = 66,6 %), indicating the plasticity of the specie to utilize plant sources. Based on growth performance, for pacu it was possible to substitute until 78,05% of FM, whereas for dourado, until 37,20%. Above these levels, there were reduction on growth performance. The increasing replacement of FM by SPC had regulatory effect on the activity of pancreatic enzymes in the first segment of the intestine of both species, measured through enzymatic assays for unspecific protease, unspecific lipase and &alpha;-amylase. It also caused a reduction on intestinal fold height of proximal intestine. All of these effects can be attributed to soybean anti-nutritional factors, especially enzyme inhibitors, whose action was enhanced when FM was completely replaced by the SPC; and the specific ability of each specie to digest / absorb plant nutrients. It is safe to infer that SPC can only be used as partial replacement of FM in diets for omnivore and carnivore fish.

Introdução: O trato gastrointestinal humano é composto por uma comunidade microbiana diversificada que atua no controle da saúde. Estudos recentes demonstraram que o equilíbrio da microbiota intestinal é afetado na doença renal crônica (DRC), ocasionando o quadro de disbiose intestinal. Estes estudos sugeriram uma associação da disbiose intestinal com complicações metabólicas como acúmulo de toxinas urêmicas, progressão da DRC, inflamação e risco cardiovascular. Diante disso, medidas com o objetivo de restaurar o equilíbrio da microbiota intestinal são sugeridas, tais como a ingestão oral de probióticos, mas poucos estudos têm abordado o efeito destes suplementos na progressão da DRC e no risco cardiovascular destes pacientes. Objetivo: Avaliar o efeito do consumo de probióticos em fatores associados com progressão da DRC e risco cardiovascular de pacientes com DRC. Material e métodos: Trata-se de um estudo clínico controlado por placebo registrado no Clinical Trials NCT03400228. O estudo incluiu 30 pacientes adultos com DRC nos estágios 3 a 5 não em diálise, com função renal estável e proteinúria igual ou superior a 500 mg. A coleta de dados ocorreu entre novembro de 2015 até dezembro de 2017. O protocolo do estudo constou de período de washout de 4 semanas e randomização dos pacientes para o grupo de intervenção (GI, suplemento com probiótico) ou para o grupo controle (GC, maltodextrina). Foi realizado avaliação basal e após 24 semanas de consumo de probiótico ou placebo. Todos os pacientes receberam a orientação de consumir 2 sachês por dia do probiótico ou do placebo (maltodextrina). Foram avaliadas variáveis demográficas, clínicas, nutricionais, hábito intestinal e exames laboratoriais com amostras sanguíneas e urinárias. Resultados: Dos 30 pacientes incluídos, 20 completaram as 24 semanas do estudo, sendo 10 no grupo intervenção e 10 no grupo placebo. Após o uso de probiótico houve aumento na taxa de filtração glomerular estimada (p<0,001) e diminuição nos níveis séricos de creatinina (p<0,001), ureia (p=0,015), proteína C reativa (p=0,03), hormônio da paratireóide (p=0,03) e potássio (p=0,012), em comparação ao grupo placebo. Os efeitos positivos do probiótico na taxa de filtração glomerular estimada e na diminuição dos níveis séricos de creatinina e ureia permaneceram após análise de regressão multivariada. Não houveram diferenças significativas nos parâmetros urinários entre os grupos. Sintomas de constipação (p<0,001) e consistência fecal (p=0,016) apresentaram melhora no grupo intervenção versus placebo. Conclusão: A suplementação de probióticos melhorou os marcadores de função renal e reduziu inflamação, além de auxiliar na melhora dos sintomas de constipação intestinal em pacientes com DRC. / Introduction: The human gastrointestinal tract is colonized by a diversified microbial community that acts in control of health. Recent studies have shown that intestinal microbiota balance is affected in chronic kidney disease (CKD) leading to intestinal dysbiosis. These studies have suggested association of intestinal dysbiosis with several metabolic disorders such as accumulation of uremic toxins, progression of CKD, inflammation and cardiovascular risk. Therefore, interventional measurement that improve intestinal microbiota balance are suggested such as supplementation of probiotics, however few studies evaluated the effect of these supplements on the progression of CKD and cardiovascular risk in CKD patients. Aim: The purpose of the study was to evaluate the effects of probiotic supplementation on the factors associated with progression of CKD and cardiovascular risk in patients with CKD. Desing and Methods: This was a randomized, double-blind, placebo-controlled study. Thirty patients with CKD stages 3 to 5 not on dialysis, with stable renal function and protein-creatinine ratio > 0.50 were included. Data collection was between November 2015 and December 2017. Study protocol was 4-week washout period, patients randomized to intervention group (IG, probiotic supplement) or control group (CG, maltodextrin), and follow for 24 weeks. Renal function, C-reactive protein (CRP), bone and mineral metabolism, nutritional, and lipid profile markers and intestinal habit were measured at baseline and 24 weeks of study. Results: From 30 patients included in this study, 20 completed the 24 study weeks, 10 in the TG and 10 in PG. After probiotic supplementation, there was increase in estimated glomerular filtration rate (p<0.001) and decrease in serum creatinine 8 (p<0.001), urea (p=0.015), C-reactive protein (p=0.030), parathyroid hormone (p=0.03), and potassium (p=0.012) levels compared to CG. The beneficials effects of probiotics on estimated glomerular filtration rate and serum creatinine, urea, and Creactive protein remained after multivariate linear regression. There were no significant differences in the urinary parameters between the two groups. Symptoms of constipation (p<0.001) and stool consistency (p=0.016) improved in IG compared to CG. Conclusion: Probiotic supplementation improved markers of renal function and reduced inflammation. In addition, it improved the symptoms of intestinal constipation in patients with CKD.

Bakgrund: Ett för tidigt fött barns tarmar och matsmältningsapparat är inte färdigutvecklade och de kan drabbas i större utsträckning av mag-tarmproblem. Att vårdpersonal har kunskap om upplevelser och stöd kring för tidigt födda barns magbesvär är viktigt. Syfte: Att beskriva för tidigt födda barns mag-tarmbesvär ur föräldrarnas perspektiv samt beskriva vilket stöd som gavs av vårdgivaren. Metod: Denna studie genomfördes med en kvalitativ innehållsanalys med deskriptiv ansats. Data analyserades med en tematisk nätverksanalys. Data bestod av loggboksblad samt skriftliga kommentarer från mödrar. Totalt antal mödrar som inkluderades i denna studie var 148, totalt antal loggboksblad var 133 och 56 skriftliga kommentarer. Resultat: Ett globalt tema, två organisationsteman samt åtta basteman identifierades. De två organisationsteman som framkom var: föräldrarnas upplevelser kring sitt för tidigt födda barn med magbesvär samt Vårdgivarens stöd och föräldrarnas upplevelse och effekt av detta stöd. Det globala temat som framkom var: Vikten av att bli lyssnad på, få stöd, och rätt information i en utsatt situation. Slutsats: Det finns ett behov av individuellt anpassat stöd hos föräldrar till för tidigt födda barn med magbesvär. Trygghet skapades då det upplevdes att vårdgivarna hade god tillgänglighet, var kunniga inom området och gav adekvata rekommendationer. Den stress och oro hos föräldrarna som barnets magbesvär medförde kunde minskas med hjälp av att bli lyssnad på, få individuellt stöd och rätt information. / Background: A prematurely born infant’s intestines and digestive system is not fully developed and may suffer of gastrointestinal problems. It is important that health care staff have knowledge of experiences and support regarding premature born infants. Purpose: To describe preterm infant’s gastrointestinal problems from a parents perspective as well as the type of support provided by medical provider. Method: The study was carried out with a qualitative/descriptive analysis of collected data. Data comprised of 133 logbook notes as well as 56 written comments from the mothers. In total 148 mothers were included in the study. Result: One global theme, two organisational themes and eight base themes were identified. The two organisational themes emerged: Parents experience of their prematurely born infant’s stomach problems and Medical providers support and parents experience and the effect of that support. The global theme emerged: The importance of being listened to, receive support and the correct information in a compromised situation. Conclusion: There is a need for individually tailored support for parents of premature infants with stomach problems. Security was created when parents experienced that the medical providers provided good accessibility, were knowledgeable in the area and made adequate recommendations. The stress and anxiety of the parents caused by the infants stomach problems could be alleviated by being listened to, receive individual support and correct information.

Počet obyvatel trpících různými infekčními, zánětlivými a alergickými nemocemi stejně jako výskyt laktózové nesnášenlivosti a vysoké hodnoty krevního cholesterolu, má narůstající tendenci. Některé z těchto zdravotních problémů jsou způsobeny nevyváženou střevní mikroflorou. Probiotika jsou pak chápána (nejen) jako potravní komponenty, které přispívají k ustanovení mikrobiální rovnováhy (Parker, 1974) mezi zdraví prospěšnými a škodlivými bakteriemi. Z tohoto důvodu, terapie založená na podávání probiotik pacientům přitáhla zájem ze strany vědců. Vhodný probiotický kmen se pak volí v závislosti na požadovaném zdravotním účinku (příp. zdravotním problému, který má být probiotickou terapií léčen). Lactobacillus plantarum 299v již prokázal své blahodárné účinky na lidech a zároveň byla i potvrzena jeho zdravotní bezpečnost, díky čemuž může tato bakterie být kategorizována jako probiotický kmen (Probi AB, Sweden). I díky tomu je Lactobacillus plantarum 299v ve značné oblibě přidáván do mnoha fukčních potravin a prodáván na trhu pod různými jmény, probiotický nápoj ProViva je jedním takovým příkladem. Cílem této práce bylo studovat fermentační proces na žitném, ječmenném a sojovém substrátu pomocí kmene Lactobacillus plantarum 299v, přičemž zvýšená pozornost byla věnována právě soji a ječmeni jako potenciálně novým substrátům pro výše uvedenou bakterii. Hlavními záměry bylo zkoumání růstu a metabolické aktivity bakterie Lactobacillus plantarum 299v v asociaci s různými cereálními substráty, a později bylo studováno totéž také ve směsi fermentované cereální komponenty s běžně dostupným ovocným džusem. K tomu, aby se dosáhlo optimálních podmínek fermentace, je třeba vzít v úvahu několik aspektů. Hlavní role při konceptování nového fermentovaného produktu patří především zpracování a taktéž kompozici surového materiálu, růstové kapacitě a produktivitě bakteriální kultury a stabilitě finálního produktu během skladování (De Vuyst, 2000). Tyto parametry jsou důležité hlavně ze strany výrobců. Krom toho jsou tu ale i zákazníci, pro něž je přijatelnost produktu založena z velké části na organoleptických vlastnostech finálního probiotického produktu, tj. aromatu a chuti. Přítomnost a dostupnost různých jednotlivých nutrientů, která byla obsažena ve fermentačním médiu výsledkem rozdílných použitých cereálních substrátů, pravděpodobně vyústila v odlišnosti metabolických drah, což pak později mohlo způsobit rozdíly v organoleptických vlastnostech finálního produktu.

In der Diagnostik der gastrointestinalen Stromatumoren (GIST) spielt neben der Histologie die Immunhistochemie eine zentrale Rolle. Die vorliegende Arbeit befasst sich mit der Fragestellung, welche Wertigkeit der Mutationsanalyse im diagnostischen Kontext zukommt und wie stabil Immunphänotyp und Mutationsstatus im Verlauf der Erkrankung tatsächlich sind. In drei Fällen rezidivierter GIST war die Histomorphologie, die Immunhistochemie und der Mutationsstatus im Vergleich zum Primärtumor stabil. Bei den untersuchten synchron auftretenden Tumoren von drei Patienten waren in der Mutationsanalyse unterschiedliche Ergebnisse zu erheben. Bei zwei Patienten unterstützte das unterschiedliche Mutationsmuster das Vorliegen synchroner Tumoren, bei einem Patienten ist das Vorliegen eines Primärtumors und einer Metastase statt einem synchronen GIST wahrscheinlich. Die Untersuchung metastasierter GIST wurde an verschiedenen Tumoren von neun Patienten durchgeführt. Acht der neun Fälle zeigten sich bezüglich der Metastasen genotypisch stabil, einer der acht Fälle wies zusätzlich einen Zugewinn einer Punktmutation auf, die als Möglichkeit eines Tumormosaiks oder als neu erworbene zusätzliche Mutation zu werten sein könnte. Zudem wurden 28 Fälle unklarer spindelzelliger Tumoren mit uneinheitlichem immunhistochemischen Profil untersucht. In Zusammenschau mit der Mutationsanalyse war eine eindeutige Bestimmung der Tumorentität möglich. Abschließend zeigt sich die Kombination aus Histomorphologie, immunhistochemischer Untersuchung und Mutationsanalyse als gutes diagnostisches Mittel zur Sicherung der Tumorentität und Entdeckung eventuell neu aufgetretener prognostisch relevanter Mutationen mit therapeutischer Konsequenz.:Inhaltsverzeichnis Abkürzungsverzeichnis 1 1. Einleitung 2 1.1 Definition und Epidemiologie 2 1.1.1 Definition 2 1.1.2 Epidemiologie 3 1.2 Histologie 3 1.2.1 Spindelzellige GIST 4 1.2.2 Epitheloide GIST 5 1.2.3 Intermediäre GIST 6 1.2.4 Mitosen 7 1.3 Immunhistochemie 8 1.4 Molekulare Pathologie 9 1.5 Klinische Diagnostik 11 1.6 Krankheitsverlauf und Risikoabschätzung 11 1.7 Therapie 13 1.7.1 Patienten mit lokalem Tumorgeschehen 13 1.7.2 Patienten mit lokal fortgeschrittenem oder metastasiertem GIST 13 2. Zielsetzung 15 3. Material und Methoden 16 3.1 Untersuchungsgut 16 3.1.1 Rezidivierte gastrointestinale Stromatumoren 16 3.1.2 Synchrone gastrointestinale Stromatumoren 16 3.1.3 Metastasierte gastrointestinale Stromatumoren 16 3.1.4 Unklare spindelzellige Tumoren 17 3.2 Chemikalien 17 3.3 Verbrauchsmaterialien 17 3.4 Chemikalien-Zusammensetzungen 18 3.5 Geräte 19 3.6 Antikörper Immunhistochemie 20 3.7 Oligonukleotide 20 3.8 Bestimmung des Risikoprofils und TNM-Klassifikation 22 3.9 Immunhistochemie 24 3.9.1 Probenaufarbeitung 25 3.9.2 Durchführung und Färbung 25 3.9.3 Auswertung und Kontrolle 26 3.10 Mutationsanalyse 27 3.10.1 Probenaufbereitung 27 3.10.2 Entparaffinierung 27 3.10.3 DNA-Extraktion 27 3.10.4 Amplifikation / Polymerase-Kettenreaktion 29 3.10.5 Konzentrationsbestimmung des PCR-Produktes 30 3.10.6 Kapillargelelektrophorese 30 3.10.7 Aufreinigung der PCR-Produkte 32 3.10.8 Sanger-Sequenzierung 32 3.10.9 Sequenzauswertung 33 4. Ergebnisse 35 4.1 Patienten mit Lokalrezidiv eines GIST 37 4.1.1 Risiko der Krankheitsprogression nach Fletcher und Miettinen 37 4.1.2 Immunhistochemie 38 4.1.3 Mutationsanalyse 38 4.2 Patienten mit synchron aufgetretenen GIST 39 4.2.1 Risiko der Krankheitsprogression nach Fletcher und Miettinen 40 4.2.2 Immunhistochemie 41 4.2.3 Mutationsanalyse 41 4.3 Patienten mit metastasiertem GIST 42 4.3.1 Risiko der Krankheitsprogression nach Fletcher und Miettinen 44 4.3.2 Immunhistochemie 45 4.3.3 Mutationsanalyse 47 4.4 Patienten mit unklaren spindelzelligen Tumoren 49 4.4.1 Risiko der Krankheitsprogression nach Fletcher und Miettinen 51 4.4.2 Immunhistochemie 53 4.4.3 Mutationsanalyse 54 5. Diskussion 57 5.1 Patienten mit Lokalrezidiv eines GIST 57 5.2 Patienten mit synchronen GIST 59 5.3 Patienten mit metastasiertem GIST 61 5.4 Patienten mit unklaren spindelzelligen Tumoren 70 Zusammenfassung 73 Tabellenverzeichnis 76 Abbildungsverzeichnis 78 Literaturverzeichnis 79 Erklärung 84 Danksagung 85 Lebenslauf 86