Dynamics of Descending Inhibition and Neuroendocrine Analgesia with special reference to the Trigeminal region

In patients with pain, it is of relevance to use clinical assessments that evaluate the pain modulation. In this thesis, the dynamics of descending inhibition or central sensitization and neuroendocrine analgesia were investigated: in healthy volunteers; in patients with chronic closed lock of the temporomandibular joint (TMJ), before and after discectomy; and finally in patients with possible neuropathic pain, (atypical odontalgia). Pain assessment was made with the eleven point numerical rating scale. The Pain thresholds were determined to evaluate central sensitization, and cold pressor tests of 2-4 °C were used to provoke descending noxious inhibitory controls. Plasma β- endorphin was determined by radioimmunoassay. The focus of evaluation was on the change induced by provocation or pain relieving surgery. In study I, we found, that with an exception for the electrical pain threshold over the central maxillary incisor, healthy volunteers increased their electrical and pressure pain thresholds during cold pressor test. There were region and stimuli specific changes between the trigeminal and the spinal region, regarding the change in pain thresholds, but no differences in respect to gender. In study II, we demonstrated that female patients, with chronic closed lock, i.e. limited jaw function and movement-evoked pain from the TMJ, had central sensitization and an elevated neuroendocrine opioid level in plasma. Study III, showed, that in 91% of female patients with chronic closed lock, the movement-evoked pain had disappeared at a median (range) of 8 (6-24) months after TMJ-discectomy. In particular, a clinically substantial reduction in pain intensity was required for a decline in plasma β-endorphin. Central sensitization showed signs to decrease in relation to relief in pain intensity. However, on the whole, central sensitization was not healed. In study IV, we noted that patients with atypical odontalgia had HPA-axis hyperactivity and altered coping together with deficient neuroendocrine opioid release and descending facilitation in the maxillary branch of the trigeminal nerve during cold pressor test. In conclusion, the outcome measure of pain relivieving surgery is feasibly a clinically substantial improvement in maximal pain intensity, here confirmed by a recovery in plasma β-endorphin. Afference from the pulp was absent from descending inhibition in healthy, and possibly promoted by descending facilitation in atypical odontalgia, indicating that the dentoalveolar region is vulnerable to development of chronic pain

Gastric acid secretion and gut peptides: mechanisms involved in inflammatory response

The regulation of gastric acid secretion is complex and involves endocrine, paracrine, and neurocrine mechanisms. Among these, the interconnecting cross-talk between different gut peptides is an important part in the control of acid secretion. The aims of this thesis were (1) to develop a new method of measuring intragastric pH for prolonged periods of time, and (2) apply developed and in-use methods using different substances and their impact on gastric acid secretion in vivo experiments on rats. (3) To study the changes in acid output and the migrating motor complex (MMC) when subjected to different substances, and (4) to further study the alterations in expression of different gut peptides in tissue samples in vitro, and the impact of inflammation in the gut. The novel Bravo model developed gave reliable recordings compared to the chronic fistula model. The pH rose during treatment with esomeprazole and the acid output in the fistula model decreased accordingly. Gut peptides ghrelin and somatostatin increased in plasma when subjected to esomeprazole treatment, while gastrin remained unchanged. Ghrelin administered in bolus doses increased the intragastric pH in accordance with previous experiments. The gut peptides somatostatin, neurotensin, and vasoactive intestinal peptide increased during pentagastrin-stimulated infusion and challenge with hydrochloric acid and polyethylene glycol both in plasma and intestinal perfusate, though the most pronounced elevation was seen in perfusate and with somatostatin. Gastrazole gave the most extensive inhibitory effect on acid secretion compared to ranitidine and esomeprazole. The CCK2-receptor antagonist YF476 inhibited acid secretion long-term and increased concentrations of ghrelin and somatostatin in plasma, but gastrin remained low. Tissue mRNA content of the peptides and their receptors were unchanged except for the ghrelin receptor. When subdued to NSAID gastrin, CCK2-receptor and iNOS increased in mRNA expression while other peptides and receptors were unchanged. Administration of NPS evoked a response in the MMC pattern with irregular spiking and prolonged cycle length of the activity fronts, and the mRNA expression of iNOS, TNF, and IL-1ß increased in the tissue. In conclusion, The Bravo model can be used as a complement to the chronic fistula model for measurements of pH. The regulation of gastric acid secretion is not only limited to the stomach, but also present in the smaller intestine where release of somatostatin seems to be most important. Different mechanisms are involved in the blockage of acid secretion when subjected to YF476, but under NSAID treatment the expression of gastrin and its receptor CCK2 increase and COX- 2 is activated which demonstrates a novel pathway for the study of gastric ulcerations. NPS, a novel neuropeptide influences the gastric motility and could have a role in inflammatory responses seen in the changes in the migrating motor complex and inflammatory markers iNOS, TNF, and IL-1ß

Effects on tumor immunity, liver, gut, lung and survival after cutaneous graft-versus-host disease regulated by photochemotherapy

The present thesis describes the effect and timing of photochemotherapy in relation to the onset and severity of cutaneous graft-versus-host (GvHD) in relation to the survival and cure of patients. Leukemia is the most common childhood malignancy and an entity of cancer that is increasing in elderly. Allogeneic stem cell transplantation following myeloablative treatment (conditioning) and using methotrexate-based prophylaxis still remains the best choice to cure of high-risk acute and relapsed chronic myeloid leukemia. To improve the long-term disease free survival, we have to redirect the adoptive immunity from GvHD towards graft-versus-leukemia (GvL). The aim of the present thesis was to test the theory postulating that effects of photochemotherapy are confined to the skin. The theory was tested by whether photochemotherapy had effects on GvHD in liver and gastrointestinal tract (GI), and if it affects the anti-tumor immunity post transplantation. The complete response in GI and liver in addition to the pulmonary mortality after photochemotherapy, which intercalate with DNA, were compared in two groups of patients. One group had received myeloablative ionizing irradiation, which leaves long-lasting DNA-breaks and the second group who received myeloablative chemotherapy including busulfan, which alkylates DNA. The effect on anti-tumor immunity was determined by the effect on the cumulative GvL with regard to whether photochemotherapy was given direct after the onset of cutaneous acute-GvHD or after a week. The main theoretical background to the present studies was the effect of photochemotherapy on cell mediated immunity evident by an inhibition of the delayed type hypersensitivity of the skin and the ability to induce circulating immunomodulatory regulatory-T cells in human. Four different patient populations were investigated; patients with cutaneous acute-GvHD; patients with cutaneous- and visceral acute-GvHD; patients with acute leukemia; and patients with chronic myeloid leukemia. Complete response, tumor immunity (GvL) and survival were considered as outcomes. Established risk factors including transplantation across the female-male barrier were assessed. The key result was the possible synergistic-effect between ionizing irradiation and photochemotherapy, which may cure GI GvHD. Furthermore, our results indicated that cutaneous acute-GvHD may enhance the anti-tumor immunity, but also the pulmonary mortality. However, cutaneous complete response to photochemotherapy may decrease the pulmonary mortality after TBI. The studies of patients with acute-leukemia and chronic- myeloid-leukemia implied that after transplantation, the adoptive tumor immunity was modulated by the timing of photochemotherapy with regards to the onset of cutaneous acute- GvHD. In conclusion, photochemotherapy has effects on disease in internal organs. The overall results suggest that the optimal time to start the photochemotherapy in patients with hematological malignancy is at least after the first week of cutaneous acute-GvHD

Circulating proteins as predictors of cardiovascular mortality in endstage renal disease

Introduction: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years). Results: In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort. Conclusions Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.Swedish Research CouncilSwedish Heart–Lung foundationEuropean Union Horizon 2020 (Grant number 634869)Dalarna UniversityUppsala UniversitySwedish Medical Research CouncilNjurfondenEuropean Union’s Horizon 2020 research and innovation programme, Marie Sklodowska-Curie Grant Agreement no. 722609Publishe

Применение программного комплекса ANSYS CFX для моделирования движения газового потока ротационной печи

Материалы XIII Междунар. науч.-техн. конф. студентов, магистрантов и молодых ученых, Гомель, 25–26 апр. 2013 г

Vargen och känslorna

I Voxnabruk i Hälsingland vågar folk inte släppa ut sina barn i skogen av rädsla för vargattacker. Samtidigt arbetar andra med att skydda den svenska vargstammen. Varför berör vargen så många, så innerligt? Hur är det egentligen att ha vargen nära - runt knuten - eller i hjärtat

Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men

Background and objectives The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied. Design, setting, participants and measurements A community-based cohort of elderly (Uppsala Longitudinal Study of Adult Men [ULSAM; n=741; mean age: 77 years]) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up. Results There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman rho=0.07, p=0.13). Higher urinary, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate (GFR), urinary albumin/creatinine ratio, and inflammatory markers interleukin 6 and high sensitivity C-reactive protein (Odds ratio for 1-standard deviation (SD) of urinary osteopontin, 1.42, 95% CI (1.00-2.02), p=0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI (1.14-1.58), p<0.001, and 1.00, 95% CI (0.79-1.26), p=0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p<0.002). Conclusions Higher urinary osteopontin specifically predicts incident chronic kidney disease while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remains to be established.Cathepsins in cardiovascular diseas

Vad behövs för ett välkomnande bemötande? - en studie om frontpersonals syn på organisatoriska förutsättningar för främjandet av värdskap i hotellverksamheter

Problembeskrivning: Majoriteten av de vetenskapliga artiklar och texter som finns kring organisatoriska förutsättningar är skrivna ur ett ledarskapsperspektiv, vilket har resulterat i en mindre kunskapslucka som lämnats öppen för vidare forskning kring ämnet. Då det är personalen som dagligen möter gästerna och förväntas skapa ett tillfredsställande servicemöte genom ett gott värdskap, är deras perspektiv väsentligt i sammanhanget. Syfte: Uppsatsens syfte är att öka förståelsen för vad receptionistanställda på hotell anser vara viktiga organisatoriska förutsättningar som behöver finnas på plats för att de ska kunna förmedla gott värdskap i sitt möte med gästen. Teori: Inom service management forskningen finns det många som tidigare har skrivit om organisatoriska förutsättningar i form av servicelandskap, empowerment och hospitality. Några av forskarna vars teorier vi analyserat tillsammans med vår empiri är Grönroos, Lashley, Goffman och Bitner. Även Hanefors samt Gunnarsson & Blohm är viktiga inslag i vår studie då de behandlar begreppet värdskap. Metod: I uppsatsen har vi använt oss av kvalitativa semistrukturerade intervjuer. Sammanlagt var det nio stycken, varav sju var djupintervjuer och två emailintervjuer som även kompletterades via telefon. Vi använde oss av bekvämlighets- samt snöbollsurval när vi valde ut frontpersonal och hade vid intervjutillfällena en intervjuguide som hjälpte oss att hålla oss inom ramen för vår undersökning. Slutsatser: Grundläggande påtagliga förutsättningar är servicelandskapet. Utan den spelar de opåtagliga faktorerna mindre roll. Vidare anser frontpersonalen att människokontakten med gäster, kollegor och ledning är absolut viktigaste i verksamheten för att kunna skapa tillfredsställande servicemöten genom ett gott bemötande. Många arbetar omedvetet med värdskap trots att begreppet inte är vida känt