Bakgrund: Inflammatorisk mag-tarmsjukdom är ett samlingsnamn för Ulcerös kolit och Crohns sjukdom. Gemensamt för sjukdomarna är att de är kroniska och att de går i skov, vilket innebär att sjukdomen är mer aktiv i vissa perioder och mindre aktiv under andra. Inflammatorisk mag-tarmsjukdom påverkar patienterna fysiskt, psykiskt och socialt, vilket påverkar deras livskvalitet. Inflammatoriska mag-tarmsjukdomar kan resultera i psykiska besvär, därför har patienterna ett behov av goda copingstrategier och en god anpassning till livet med sjukdomen. Genom evidensbaserad och personcentrerad vård har sjuksköterskan en stödjande funktion i vården av dessa patienter.  Syfte: Syftet med litteraturstudien var att undersöka patienternas upplevelser av att leva med inflammatorisk mag-tarmsjukdom för att kunna belysa deras behov av stöd. Metod: En litteraturstudie med boolesk sökteknik gjordes i databaserna Cinahl, PubMed och PsycINFO där tio artiklar valdes ut genom granskning med SBU:s granskningsmall.    Resultat: När resultatet av tio artiklar sammanställts framkom fyra teman; patienters upplevelser av att leva med inflammatorisk mag-tarmsjukdom, patienternas behov av stöd, stöd i att acceptera och leva med sjukdomen samt stöd i form av utbildning. Slutsats: Patienter med inflammatorisk mag-tarmsjukdom har behov av stöd både fysiskt, psykiskt och socialt, från både sjukvårdspersonal och anhöriga. Patienterna har ett behov av stöd i form av information, undervisning samt psykiskt och emotionellt stöd. Sjuksköterskans stöd genom personcentrerad och empatisk kommunikation hjälper patienterna att acceptera sjukdomen och deras “nya normala”, vilket främjar deras självständighet, självkännedom och eget ansvar i sjukdomshanteringen. Patientutbildning bidrar till bättre egenvårdsstrategier, ökad följsamhet till behandling och livsstils anpassningar, vilket även bidrar till ökat självförtroende och välmående.

Inflammatory bowel disease is a serious condition with an incomplete etiology and pathogenesis. In this thesis, a mouse model of sodium dextran sulfate-induced inflammation was used to study different changes in the metabolism of germ-free and conventionally raised mice due to the development of the inflammatory process. NMR metabolomics of fecal, urine and serum samples, combined with uni- and multivariate statistical analysis, were used to characterize the changes. It was shown that the metabolic signature differs between germ-free and conventional mice. In germ-free mice, significant amounts of carbohydrates were found in feces. Their levels decreased during inflammation as they were excreted in urine. In contrast to conventional mice, germ-free mice also excreted large amounts of amino acids in feces during the developing inflammation. Disorders of sugar and protein metabolism found in germ-free mice indicate severe malnutrition caused by inflammation. The results show that the presence of a microbiome represents a protective mechanism against significant disruption in the body. A stability study of fecal extracts of healthy conventionally colonized mice confirmed that none of the identified and quantified metabolites showed significant systemic changes in several consecutively collected...

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Tesis por compendio / [ES] La presente tesis doctoral titulada "Sistemas de liberacio'n controlada de fa'rmacos diseñados para mejorar el tratamiento de Enfermedad Inflamatoria Intestinal" se centra en el diseño, preparación, caracterización y evaluación in vivo de distintos sistemas de liberación controlada de fármacos en colon (CDDS, por sus siglas en inglés) utilizando como soporte micropartículas de silice mesoporosa, funcionalizadas con puertas moleculares. En conclusión, los estudios realizados demuestran que los materiales de silice mesoporosa, en combinación con puertas moleculares sensibles a estímulos específicos, tienen un gran potencial para el desarrollo de nuevos sistemas de liberación controlada de fármacos en el colon, dirigidos a mejorar el arsenal terapéutico disponible para el tratamiento de EII. La posibilidad de adaptar o personalizar la carga y las puertas moleculares hace que estos soportes de sílice mesoporosa sean una opción interesante para el desarrollo de nuevos sistemas de liberación controlada de fármacos en diferentes aplicaciones biomédicas. Finalmente, esperamos que los resultados obtenidos en esta tesis doctoral sirvan de inspiración para el desarrollo de sistemas de liberación controlada de fármacos innovadores y cada vez más inteligentes, para su aplicación tanto en medicina como en otras áreas. / [CA] La present tesi doctoral titulada "Sistemes d'alliberament controlat de farmacs dissenyats per a millorar el tractament de Malaltia Inflamatoria Intestinal" se centra en el disseny, preparacio, caracteritzacio i avaluacio in vivo de diferents sistemes d'alliberament controlat de farmacs en colon (*CDDS, per les seues sigles en angles) utilitzant com a suport microparticules de si'lice mesoporosa, funcionalitzades amb portes moleculars. En conclusio, els estudis realitzats demostren que els materials de si'lice mesoporosa, en combinacio amb portes moleculars sensibles a estimuls especifics, tenen un gran potencial per al desenvolupament de nous sistemes d'alliberament controlat de farmacs en el colon, dirigits a millorar l'arsenal terapeutic disponible per al tractament de MII. La possibilitat d'adaptar o personalitzar la carrega i les portes moleculars, fa que aquests suports de silice mesoporosa siguen una opcio interessant per al desenvolupament de nous sistemes d'alliberacio controlada de farmacs en diferents aplicacions biomediques. Finalment, esperem que els resultats obtinguts en aquesta tesi doctoral servisquen d'inspiracio per al desenvolupament de sistemes d'alliberament controlat de farmacs innovadors i cada vegada mes intel·ligents, per a la seua aplicacio tant en medicina com en altres arees. / [EN] This PhD thesis entitled "Smart drug delivery systems designed to improve Inflammatory Bowel Disease therapy" is focused on the design, synthesis, characterization and in vivo evaluation of several Colon Drug Delivery Systems (CDDS) using hybrid mesoporous silica microparticles as scaffolds containing molecular gates. In conclusion, the studies shown in this Thesis demonstrate that mesoporous silica materials in combination with responsive molecular gates have great potential in the design and preparation of new CDDS to improve the therapeutic options available for IBD. The possibility to adapt the cargo and the molecular gate makes mesoporous silica support especially appealing for similar controlled drug delivery applications in the biomedical field. We hope that the obtained results could inspire the development of new innovative smart drug delivery systems in this or other fields. / We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. AHT thanks to the Spanish MEC for his FPU grant. We thank the Generalitat Valenciana (Project PROMETEO2018/024) / Hernández Teruel, A. (2019). Smart drug delivery systems designed to improve Inflammatory Bowel Disease therapy [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/129863 / TESIS / Compendio

<p>Miniaturization of technologies to milli-, micro- and nanoscale offers numerous advantages for diagnostic and therapeutic biomedical applications. In comparison to their macro-scale counterparts, these small-scale systems are more portable, less invasive and less costly. They can facilitate rapid, sensitive and high throughput detection of abnormalities, help track disease progression, reduce sample consumption and improve therapeutic efficacy of drug delivery while decreasing systemic toxicity. Thus, there is clearly a need for creating innovative milli-, micro- and nanoscale tools that can uncover new possibilities in detection and treatment of various types of diseases. The overall objective of this dissertation was to develop novel small-scale technologies that could help enhance diagnostic and/or therapeutic outcomes in patients with cancer, opioid addiction and inflammatory bowel disease. First, we developed an echogenically stable nanodroplet ultrasound contrast agent with potential applications in extravascular molecular imaging of tumors and targeted cancer therapies. Then, we created a polymer blend microsphere system that could be integrated in prescription opioid tablets to develop an abuse-deterrent formulation against smoking. Finally, we designed a release system for localized delivery of aminosalicylates from magnetically actuated millirobots in the colon to improve therapeutic outcomes in patients suffering from inflammatory bowel disease. Overall, the technologies we developed could serve as a basis for designing diagnostic and therapeutic tools that are superior to currently existing platforms.</p>

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In the present investigation peripheral blood lymphocytes from patients with inflammatory bowel disease (IBD) and different cancer states were treated with various agents and compared with lymphocytes from healthy control individuals (HCI) treated in the same way and measured in the Comet assay. For inflammatory bowel disease, patient¿s responses in IBD patients treated with H2O2 were higher than in HCI and crohn¿s patients (CD) were found to have higher responses than Ulcerative colitis (UC) patients. The responses for all IBD and HCI were all reduced in the presence of chaga mushroom extract which behaved in an antioxidant manner. A second group of IBD patients were treated with the heterocyclic amine (food mutagen), IQ and H2O2 and responses were reduced in the presence of the flavonoids, quercetin and epicatechin and compared with HCI similarity treated. In all cells responses were reduced with flavonoids and again CD had higher responses than the UC patients and IBD patients higher than HCI. The responses with CD and UC were that confirmed in two independent studies with IBD, one with chaga mushroom extract and the other with flavonoids. Peripheral lymphocytes from malignant melanoma and suspected melanoma patients and colon cancer and polyposis patients were compared to the lymphocytes from HCI and treated with UVA. There were differential sensitivities when measured in the micronucleus and Comet assays. The cancer patients had higher responses than those in the precancerous states and they in turn were higher than responses in HCI. In all the studies, untreated baseline DNA damage values were also higher in IBD and cancer patients and pre-cancerous patients than HCIs. This would suggest that baseline frequencies of different diseases compared to controls could be an important biomarker in the diagnosis of pre-cancers and early stage cancers. Also peripheral lymphocytes are a useful surrogate for cancers and pre-cancerous disease states since, blood is present in all organs and tissues and DNA is basically the same in all cells.

<p>Intestinal microbiota are key determinants of gut homeostasis and affect various gut physiological and immune processes. Co-evolution has enabled the host and intestinal microbes to exist in a mutualistic relationship. However, interactions between the host and its intestinal microbiota exist in a delicate balance between mutualism and pathogenicity. Maintenance or disruption of this balance depends on a complex interplay between the microbiota and the host, as well as other gut luminal factors, including diet, that are poorly understood. The main goal of this thesis has been to study the host-gut luminal interactions that regulate gut physiology and immunity. In particular, <strong>Chapter 2</strong> centers on investigating the effect of perturbing the intestinal barrier using a non-steroidal inflammatory drug on host-microbial and dietary interactions in a mouse model of gluten sensitivity. I demonstrated that indomethacin-induced increase in intestinal permeability is associated with altered intestinal microbiota composition, systemic antibody development against intestinal bacteria and a shift in immune responses to the dietary antigen, gluten. <strong>Chapter 3</strong> focuses on investigating whether modulation of the intestinal microbiota can affect the host’s susceptibility to intestinal injury. I used mice with defective intracellular bacterial receptor signaling because discrimination between commensals and pathogens is, in part, achieved by a family of receptors that recognize conserved bacterial components. I demonstrated that the microbiota with which these mice are colonized influences the expression of RegIII-γ, a type of antimicrobial peptide, and susceptibility to intestinal injury. To gain further insight on the effect of microbiota on antimicrobial peptides, in <strong>Chapter 4</strong> we conducted a combination of gnotobiotic and <em>in-vitro</em> experiments where we identified that specific components of the microbiota differentially regulate RegIII expression. Further examination showed that <em>MyD88 a</em>nd <em>Ticam1 </em>genes, which are signaling adaptor proteins of pattern recognition receptors, are essential regulators of microbial–induced RegIII expression by intestinal epithelial cells. Collectively, the work presented in this thesis provides novel insight on the bi-directional interaction between the host and the gut luminal content as well as of potential beneficial effects of microbiota-modulating strategies in maintaining homeostasis and preventing disease.</p> / Doctor of Philosophy (Medical Science)

For most children, occult vascular damage is minimal and has a slow rate of progression likely due to the existence of healthy lifestyles and the prevalence of preventative behaviours. However, there is evidence to suggest a marked increase in the prevalence of traditional and emerging cardiovascular risk factors in children with chronic inflammatory conditions due to the common aetiology pathways of inflammation and atherosclerosis. In the current cross-sectional study, a comprehensive vascular assessment was conducted on 21 children with various chronic inflammatory conditions including juvenile idiopathic arthritis (JIA), cystic fibrosis (CF), type I diabetes mellitus (T1DM) and inflammatory bowel disease (IBD) (CIC, 12.7 ± 2.3 years) compared to 9 healthy, age and sex- matched controls (CON, 13.1 ± 1.8 years). B-mode ultrasound images were used to assess carotid artery intima media thickness (cIMT) as well as local arterial stiffness through measurement of compliance and distensibility with the use of concurrent applanation tonometry. Whole-body arterial stiffness was measured by assessing pulse wave velocity (PWV) between the carotid and dorsalis pedis arteries. A brachial flow mediated dilation (FMD) test was implemented to assess endothelial function of the brachial artery. Twelve hour-fasted blood samples were collected and analyzed for blood lipids and an acute inflammatory marker, C-reactive protein (CRP). There were no group differences in cIMT (p=0.18), distensibility (p=0.40), compliance (p=0.88), whole body PWV (p=0.74) or LDL- cholesterol (p=0.99). The CIC group demonstrated significantly lower FMD when iii compared to CON (p=0.01). There were no group differences in inflammatory levels, as indicated by concentration of CRP (p=0.63). Sub-analyses revealed similar cIMT, distensibility, compliance, PWV and LDL levels between children with JIA (n=11, 12.6 ± 2.9 years), CON (n=9, 13.1 ± 1.8 years) and the other inflammatory conditions (INFL, n=10, 12.4 ± 1.7 years). Both JIA and INFL reported lower FMD when compared to CON (p=0.04). INFL had lower BMI compared to JIA and CON (p=0.02). The primary findings from this study suggest that arterial structure is similar between children with a CIC and their healthy peers; however, arterial function, as indicated by FMD (%), was reduced in the CIC group. This finding is essential in that it helps to identify an area for targeted intervention and/or prevention of future CV events as endothelial dysfunction is known to be an early event in the pathophysiology of atherosclerosis. / Thesis / Master of Science (MSc)

Bakgrund: Inflammatorisk tarmsjukdom innefattar både ulcerös kolit och Crohns sjukdom, vilka är kroniska inflammatoriska tarmsjukdomar. De båda sjukdomarna löper i skov med plötsliga försämringsperioder och långa perioder utan besvär. Det är viktigt att sjuksköterskan vidtar specifika omvårdnadsåtgärder samt förhåller sig personcentrerat där värden som värdighet bevaras för att stödja personen. Syfte: Att beskriva personers erfarenheter av att leva med inflammatorisk tarmsjukdom. Metod: Till metod valdes en litteraturöversikt och de databaser som användes var PubMed samt Cinahl Complete. Inklusionskriterier var vetenskapliga originalartiklar, genomgått peer-review, engelskt språk samt publicerade från år 2014 till 2024. Genom ett systematiskt urval arbetades tio artiklar fram, varav nio med kvalitativ design och en med mixad metod. Resultat: I litteraturöversiktens resultat framkom det att personer med inflammatorisk tarmsjukdom hade erfarenheten av att sjukdomen påverkade deras dagliga liv, både i det sociala livet och yrkeskarriären. Personer med inflammatorisk tarmsjukdom hade även erfarenheter att sjukdomen påverkade det emotionella välbefinnandet. Det lyftes även fram hur personer hanterade sjukdomen, vilka strategier som användes och stödets betydelse beskrevs. Slutsats: Litteraturöversikten visade att personer med inflammatorisk tarmsjukdom möter utmaningar inom många områden i livet. På grund av de anpassningar som individen måste genomgå är det viktigt att sjuksköterskan bidrar med stöd för att möjliggöra effektiv sjukdomshantering. Roys adaptionsteori kan ge sjuksköterskan en bättre förståelse för personernas anpassningsförmåga och kompensera med stöd för att hälsa och livskvalité ska upprätthållas. / Background: Inflammatory bowel disease encompasses both ulcerative colitis and Crohn's Disease, which are chronic inflammatory bowel diseases. Both diseases are characterized by periods of flare-ups with sudden exacerbations and long periods of remission. It is important for nurses to implement specific nursing interventions and to maintain a person-centered approach where values like dignity are preserved to support the person. Aim: To describe people's experiences of living with inflammatory bowel disease. Method: The chosen method was a literature review, with PubMed and CINAHL Complete as the selected databases. Inclusion criteria were scientific original articles that had undergone peer review, were in English, and were published from 2014 onwards. Through a systematic selection process, ten articles were identified, of which nine had a qualitative design and one used mixed methods. Results: In the results of the literature review, it was found that individuals with inflammatory bowel disease experienced the impact of the disease on their daily lives, including their social life and professional careers. They also reported that the disease affected their emotional well-being. Additionally, the review highlighted how individuals managed the disease, the strategies they used, and the significance of support. Conclusion: The literature review showed that individuals with inflammatory bowel disease face challenges in many areas of life. Due to the adaptations that the individual must undergo, it is important for nurses to provide support to enable effective disease management. Roy`s adaption theory can provide the nurse with a better understanding of individual`s adaptability and compensate with support to maintain health and quality of life.