Kinetics of the cellular immune response following closed head injury

Background Tube-feeding or nutritional support is a therapy for people who can’t get enough nutrition by eating or drinking. You may need it if you have difficulty swallowing, loss of appetite, are severely malnourished or have inability to absorb nutrients through your digestive system. There are several diagnoses associated with tube-feeding, depending on the persons diagnose and users state the user can be tied to the tube-feeding equipment from 3 to 18 hours a day. In Sweden there are around 1500-3000 adults in need of tube-feeding outside the hospitals.   Method This report is made by Cindy Sjöblom and is an individual student’s work. The project is her dissertation and final project at the two year Masters program Advanced Product Design at Umeå Institute of Design. The project has been executed during 20 weeks the spring 2015. The project is based on the design process which includes the following phases; Research & Analysing, Ideation & Concept’s and Detailing & Visualization. The Research & Analysis phase has included; Product analysis, user interviews & observations, market outlook, anatomical knowledge, problem listing and opportunity findings. The Ideation & Concept’s phase has included; Inspiration, persona creation, creative workshop, sketching, concepts creation, mock-up building, user testing & feedback. The Detailing & Visualization phase has included; 3D modelling, moodboard creation, sketching, final model building, photo shooting, video recording, documentation, presentation and a poster and exhibition stand at Umeå Institute of Design and at Semcon, Gothenburg. Result Tubie is an ambulatory tube-feeding system to facilitate an active everyday life for people in need of enteral nutrition. Tubie consists out of six parts; A nutrition pump and a wireless charging station, a nutrition bag and an external tubing, a wearable waist band and an application for a smart device to be able to control the pump. Unlike traditional enteral nutritions systems, Tubie is designed with a focus on the users in a home environment and their need for a more active lifestyle and discreet usage in social environments. Tubie is simply discreet due to its wearable features that allows the user to wear it underneath the clothing as well as control the pump via a smart device with an adaptable pre-alarm that sounds like any other text message or ring tone

Serum MASP-1 in complex with MBL activates endothelial cells.

The complement system plays an important role in the induction of inflammation. In this study we demonstrate that the initiation complexes of the lectin pathway, consisting of mannose-binding lectin (MBL) and associated serine proteases (MASPs) elicit Ca2+ signaling in cultured endothelial cells (HUVECs). This is in agreement with our previous results showing that the recombinant catalytic fragment of MASP-1 activates endothelial cells by cleaving protease activated receptor 4. Two other proteases, MASP-2 and MASP-3 are also associated with MBL. Earlier we showed that recombinant catalytic fragment of MASP-2 cannot activate HUVECs, and in this study we demonstrate that the same fragment of MASP-3 has also no effect. We find the same to be the case if we use recombinant forms of the N-terminal parts of MASP-1 and MASP-2 which only contain non-enzymatic domains. Moreover, stable zymogen mutant form of MASP-1 was also ineffective to stimulate endothelial cells, which suggests that in vivo MASP-1 have the ability to activate endothelial cells directly as well as to activate the lectin pathway simultaneously. We show that among the components of the MBL-MASPs complexes only MASP-1 is able to trigger response in HUVECs and the proteolytic activity of MASP-1 is essential. Our results strengthen the view that MASP-1 plays a central role in the early innate immune response

MASP-1 Increases Endothelial Permeability

Pathologically increased vascular permeability is an important dysfunction in the pathomechanism of life-threatening conditions, such as sepsis, ischemia/reperfusion, or hereditary angioedema (HAE), diseases accompanied by uncontrolled activation of the complement system. HAE for example is caused by the deficiency of C1-inhibitor (the main regulator of early complement activation), which leads to edematous attacks threatening with circulatory collapse. We have previously reported that endothelial cells become activated during HAE attacks. A natural target of C1-inhibitor is mannan-binding lectin-associated serine protease-1 (MASP-1), a multifunctional serine protease, which plays a key role in the activation of complement lectin pathway. We have previously shown that MASP-1 induces the pro-inflammatory activation of endothelial cells and in this study we investigated whether MASP-1 can directly affect endothelial permeability. All experiments were performed on human umbilical vein endothelial cells (HUVECs). Real-time micro electric sensing revealed that MASP-1 decreases the impedance of HUVEC monolayers and in a recently developed permeability test (XperT), MASP-1 dose-dependently increased endothelial paracellular transport. We show that protease activated receptor-1 mediated intracellular Ca2+-mobilization, Rho-kinase activation dependent myosin light chain (MLC) phosphorylation, cytoskeletal actin rearrangement, and disruption of interendothelial junctions are underlying this phenomenon. Furthermore, in a whole-transcriptome microarray analysis MASP-1 significantly changed the expression of 25 permeability-related genes in HUVECs—for example it up-regulated bradykinin B2 receptor expression. According to our results, MASP-1 has potent permeability increasing effects. During infections or injuries MASP-1 may help eliminate the microbes and/or tissue debris by enhancing the extravasation of soluble and cellular components of the immune system, however, it may also play a role in the pathomechanism of diseases, where edema formation and complement lectin pathway activation are simultaneously present. Our findings also raise the possibility that MASP-1 may be a promising target of anti-edema drug development

Comparative immunohistochemical study of the effects of pilocarpine on the mossy cells, mossy fibres and inhibitory neurones in murine dentate gyrus

Treatment with pilocarpine (PILO) induces variable degrees of loss of mossy cells (MCs) and mossy fibre (MF) sprouting in rodents, the relationships of which have not been examined in individual animals. Our aim was to test whether the loss of MCs and MF sprouting are coupled processes in PILO-treated rodents. Animals which exhibited intense PILO-induced convulsions for at least 30 min were used in this study. After a 2-month survival period, the incidence of epileptic seizures was checked individually by neuropeptide-Y (NPY) immunohistochemistry, and the numbers of MCs were counted by means of immunohistochemistry, for calretinin (CR) in mice and calcitonin gene-related peptide (CGRP) in rats. MF sprouting was checked by using Timm's silver-sulphide method for zinc. In our comparative studies, NPY immunohistochemistry resulted in more positive animals than on zinc staining. The CR immunoreactivity remained unchanged even in those mice that displayed MF sprouting and greatly increased NPY immunoreactivity. CR immunoreactivity was also verified after transection of the fornix to exclude the extrahippocampal source of this peptide. However, the CGRP immunoreactivity was severely reduced in those rats that exhibited simultaneous increases in zinc content and NPY immunoreactivity in the supragranular layer and stratum lucidum. Our findings suggest that the MCs survive PILO treatment in mice, but not in rats. There is direct evidence of a close relationship between the loss of MCs and MF sprouting in rats, but not in mice. Thus, similar PILO seizures may result from different changes in the neuronal circuits of rodents