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Coming dissertations at MedFak

  • Gastrointestinal Permeability and Motility in Inflammatory Bowel Disease Author: Anas Kh. Al-Saffar Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-382486 Publication date: 2019-05-23 14:07

    Synchronized motility, permeability and secretory (hormones and enzymes) events are integral to normal physiology. Smooth muscle syncytium operates with enteric nervous system (ENS) and endocrine signalling to accommodate, mix and control passage of ingested materials. The intestinal epithelial cells (IECs) drive digestion and absorption while repelling harmful compounds.

    This thesis investigated GI barrier function (permeability, mucosal integrity), motility and hormonal patterns in inflammatory bowel disease (IBD) by: 1) assessing GI motility using a wireless motility capsule (WMC, SmartPill®) and video capsule endoscopy (VCE, Pillcam®), 2) investigation of intestinal fatty acid binding protein (I-FABP) as a biomarker of Crohn’s disease (CD) disease activity, 3) evaluation of small intestinal permeability in IBD, 4) investigating meal-related WMC motility and simultaneous hormonal (e.g., Ghrelin, GLP-1, GIP, PYY) patterns in IBD. Reference WMC motility values for transit times for gastric emptying, small bowel, orocecal, small+large bowel, colon and whole gut were established. Software-generated estimates and visually determined values were nearly identical. Compared with VCE estimates (represents fasting conditions), the WMC records longer GET and SBTT. Variations in intra-subject reproducibility must be considered in clinical investigations. This data was then used to investigate IBD patients. I-FABP was primarily expressed in the epithelium of the small bowel and to lesser extent also in the colon and stomach. Circulating I-FABP was elevated in active CD with a magnitude comparable to TNFα. I-FABP lowers and rises again in parallel with TNFα and HBI during infliximab treatment. I-FABP can be used as a jejunum and ileum selective prognostic biomarker for monitoring disease activity. Increased small intestine mucosal barrier permeability to lactulose in both CD and UC was found. Sucralose can serve a dual purpose in quantifying small and large intestinal permeability. Small intestinal hyper-permeability was not revealed as a transporter dependent nutrient (riboflavin) malabsorption. Using the WMC, consistent motility disturbances in IBD were limited, as were differences in pH. However, disturbances within many individuals were found. As part of the investigation, defects in gut peptide and metabolic hormone meal responses were found, typically higher plasma levels. No clear associations between hormones and motility were found. Effects on hunger/satiety signaling in IBD are anticipated.

    The present thesis shows the utility of the WMC and gut barrier tests in monitoring IBD patients.

  • Precise cell manipulations and imaging of cellular responses : Methods developed using microfluidic, 3D-printing and microfabrication technologies Author: Nikos Fatsis-Kavalopoulos Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-382277 Publication date: 2019-05-22 10:29

    It is at the heart of biological and medical research to try and understand how cells communicate with each other, and how cells respond to alterations in their environment, including treatment with different drugs. There is in this context a continued need for better methods that allow researchers to precisely manipulate cells and their microenvironment and to study the resulting responses using high-resolution live microscopy. This thesis presents the development and implementation of several devices that addresses these needs.

    A novel microfluidic device called the cell assembly generator (CAGE) was created to generate precisely composed cell clusters of different cell types; the first of its kind. Experimental evidence demonstrated that the CAGE chip can be used to study paracrine signalling in tailor-made cancer cell clusters composed of up to five cells.

    A high-throughput microfluidic chip for rapid phenotypic antibiotic susceptibility testing was developed and tested using 21 clinical isolates of Klebsiella pneumoniae, Staphylococcus aureus and Escherichia coli against a panel of antibiotics. Stable minimum inhibitory concentration values were obtained from this system within 2-4 hours with high accuracy to the standard method.

    3D-printing was used to create a modular and affordable time-lapse imaging and incubation system, called ATLIS. This system enables researchers to convert simple inverted microscopes into live cell imaging systems, where images and movies of living cells can be recorded using a regular smartphone.

    Finally, a strategy was developed for the generation of modular microfluidic systems using 3D-printed moulds for PDMS casting, to enable studies of leukocyte adherence to differentially treated endothelial cell populations in the same field of view and under the same conditions.

  • Seasonal aspects of peripartum depressive symptoms Author: Hanna E. Henriksson Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-381426 Publication date: 2019-05-21 13:08

    Every year, a large proportion of pregnant and newly delivered women develop peripartum depression, a condition that may cause long-term suffering for the entire family. Although there is a lack of consensus, some studies propose an association between season and the risk of developing depression during pregnancy and the postpartum period. Furthermore, the immune system, which undergoes numerous structural changes during pregnancy, has been suggested to exhibit seasonal variations. In addition, discrepancies in metabolic profiles have been reported between women with and without depression after childbirth. This thesis aimed to investigate seasonal aspects of peripartum depressive symptoms (PPDS) and biological markers during the peripartum period. The data mainly derived from the prospective population-based Biology, Affect, Stress, Imaging, and Cognition (BASIC) study, but data were also included from the longitudinal population-based Uppsala-Athens (UPPSAT) study. The presence of depressive symptoms was primarily assessed using the Edinburgh Postnatal Depression Scale (EPDS). There were no consistent associations between season, meteorological parameters, air pollen count, and PPDS. Moreover, a number of inflammatory markers were identified as having seasonal variations among samples from pregnant women. On the contrary, only one marker had a seasonal pattern during the early postpartum period. Furthermore, metabolic profiles were not discriminatory between pregnant women with and without depressive symptoms. However, when divided into summer and winter childbirths, discrepancies were identified in metabolic profiles between summer cases and controls, as well as between summer and winter controls. In summary, the studies included in this thesis suggest that season, specifically, is not associated with PPDS. However, season may have a moderating effect on the association between depressive symptoms and the metabolic profile of pregnant women. In addition, the seasonal variations appears more prominent among inflammatory markers during late pregnancy, compared with the early postpartum period. These findings suggest that women need equal attention in clinical care regardless of the season during which they give birth. Future studies on biological aspects of PPDS and immune-associated conditions are encouraged to also assess seasonality.

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