50 research outputs found
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
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
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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