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Model reliability is important when groundwater models are used for evaluation of environmental impact and water resource management. Model attributes such as geohydrologic units and parameter values need to be quantified in order to obtain reliable results. A primary objective of sampling design for groundwater models is to increase the reliability of modelling results by selecting effective measurement locations and times. It is advantageous to employ simulation models to guide measurement strategies already in early investigation stages. Normally, optimal design is only possible when model attributes are known prior to constructing a design. This is not a meaningful requirement as the model attributes are the final result of the analysis and are not known beforehand. Thus, robust design methods are required that are effective for ranges of parameter values, measurement error types and for alternative conceptual models. Parameter sensitivity is the fundamental model property that is used in this thesis to create effective designs. For conceptual model uncertainty, large-scale sensitivity analysis is used to devise networks that capture sufficient information to determine which model best describes the system with a minimum of measurement points. In fixed conceptual models, effective parameter- and error-robust designs are based on criteria that minimise the size of the parameter covariance matrix (D-optimality). Optimal designs do not necessarily have observations with the highest parameter sensitivities because D-optimality reduces parameter estimation errors by balancing high sensitivity and low correlation between parameters. Ignoring correlation in sparse designs may result in considerably inefficient designs. Different measurement error assumptions may also give widely different optimal designs. Early stage design often involves simple homogenous models for which the design effectiveness may be seriously offset by significant aquifer heterogeneity. Simple automatic and manual methods are possible for design generation. While none of these guarantee globally optimal designs, they do generate designs that are more effective than those normally used for measurement programs. Effective designs are seldom intuitively obvious, indicating that this methodology is quite useful. A general benefit of this type of analysis, in addition to the actual generation of designs, is insight into the relative importance of model attributes and their relation to different measurement strategies.
91-554-5040-7 / Link / Nordqvist , Rune / 2001

Uppsala universitet Historieämnen
This is a historiographical study of how the Swedish Social Democracy has described both its own and Sweden's history during the period 1892-2000. The Social Democratic endeavour to attain hegemony and struggle for the public view of history is focused. The study concerns how the intellectuals of the Social Democrats, both nationally and internally - within the party, labour movement and working class - have used historiography as an ideological resource of power. The dissertation gives a perspective on the discourse of a "Social Democratic hegemony" in Sweden. It presents the problem, with historiography as an example, how the bourgeois hegemony is reconstructed when the alternative hegemonic labour movement enters the historical scene and later obtains a state-controlling position. How have the mechanisms been constructed, what is the role of the social democracy and historiography in this process, inside the social democracy itself?
91-89044-78-9 / Link / Linderborg , Åsa / 2001

Traumatic brain injury (TBI) is a major cause of mortality and disability. As common sequelae in survivors of TBI are disabling functional, emotional and cognitive disturbances, improved treatment of TBI patients is urgently needed. At present, no neuroprotective pharmacological treatment exists. The formation of oxygen-centered free radicals, reactive oxygen species (ROS), is considered an important event in the pathophysiology of TBI. In the present thesis, the fluid percussion (FPI) and controlled cortical contusion injury models of TBI in rats were used. Two nitrone radical scavengers, α-Phenyl-N-tert -butyl nitrone (PBN) and the sulfonated analogue of PBN, 2-sulfophenyl-N-tert-butyl nitrone (S-PBN), were used as tools to study the role of ROS in TBI.Pre-treatment with PBN (30 mg/kg) improved morphological and cognitive outcome after severe controlled cortical contusion injury. Treatment with equimolar doses of PBN and S-PBN administered 30 min after FPI followed by a 24 h intravenous infusion improved morphological outcome. Only S-PBN improved cognitive outcome as assessed in the Morris Water Maze. Surprisingly, pre-treatment with PBN increased the number of apoptotic neurons at 24 hours after injury despite a reduced lesion volume. FPI resulted in an early increase in glucose uptake and a reduction in regional cerebral blood flow (rCBF) assessed by fluoro-2-deoxyglucose (FDG) and hexamethylpropylene amine oxime (HMPAO) autoradiography. At 12 h, a marked reduction in glucose uptake and rCBF ensued. These TBI-induced changes were attenuated by PBN and S-PBN pre-treatment.A method for ROS detection using 4-hydroxybenzoate in conjunction with microdialysis was evaluated. The results showed a marked increase in ROS formation as assessed by an increase in the single adduct 3,4-DHBA, lasting 90 min after injury. In a separate study, PBN and S-PBN equally reduced 3,4-DHBA formation despite no detectable brain concentrations of S-PBN at 30 or 60 min post-injury.In conclusion, ROS play an important role in the injury process after TBI. We report a method for ROS detection with potential clinical utility. Nitrones increased ROS elimination and improved functional and morphological outcome. Nitrone treatment may have a clinical potential as a neuroprotective concept in TBI.
91-554-5053-9 / Link / Marklund , Niklas / 2001

Electromagnetic fields from distant radio transmitters interact with the resistivity structures in the earth. They can be regarded as plane-wave fields since their penetration depth is much smaller than their wavelength. In this thesis, plane wave methods have been applied in a number of novel ways to map the resistivity of the bedrock and the sedimentary overburden. The main objective of the field measurements carried out was to map and characterise fault and fracture zones in several areas in northern Sweden. Two different techniques have been applied, the radiomagnetotelluric (RMT) method and the radiofrequency electromagnetic (RF-EM) method. These methods utilise frequencies in both the very low frequency band (VLF, 3-30 kHz) and the low frequency band (LF, 30-300 kHz). They are extensions of the traditional VLF method, which has been widely used for detection of fracture zones in the bedrock and for groundwater exploration. The broader frequency range used in the RMT and RF-EM methods makes it possible to resolve variations of resistivity with depth in addition to lateral variations. A recently developed 2D-inversion scheme for plane-wave excitations of the ground was applied for the interpretation of the data. The computer program was originally developed for the interpretation of low frequency magnetotelluric data. It was found that the 2D-code is a fast and convenient way for quantitative interpretations of both the RMT and the RF-EM data. The results show that detailed information concerning resistivity distribution in the ground down to several hundred meters in the bedrock can be obtained. Fracture zones in the bedrock can be identified and their resistivity, width and dip can be determined.
91-554-5028-8 / Link / Persson , Lena / 2001

Uppsala universitet Neurologi
The treatment strategy for skull base meningiomas remains a controversial issue. Because of the proximity of these tumours to critical neurovascular structures, the risk for vascular damage and new cranial neuropathies postoperatively is significant. To avoid unacceptable neurological deficits the surgical treatment strategy includes different surgical approaches and a subtotal removal of these tumours in some cases. However, because the rate of recurrence and progression is significant in these patients, a demand for adjuvant treatment and better prognostic methods is called for so that treatment and follow-up can be tailored to each patient.Accordingly, we have chosen to evaluate general outcome and facial nerve function after translabyrinthine and transcochlear approaches for cerebellopontine angle (CPA) meningiomas. Furthermore, we have evaluated two adjuvant treatments, namely, irradiation by high-energy proton beams and medical treatment with interferon-alpha as well as evaluation of the treatment effect with 11C-L-methionine PET. In addition, we have evaluated a new PET tracer (76Br-BrdU) for "in vivo" determination of the growth potential of intracranial tumours.Conclusion: The translabyrinthine and transcochlear approaches are apparently safe surgical procedures in the treatment of CPA meningiomas. Proton beam therapy is technically feasible as suggested by the fact that only minimal side effects were observed. Moreover, none of the meningiomas treated have shown progression during a 36-month follow-up. Our results indicate that IFN-alpha can be an effective oncostatic treatment for certain patients with meningiomas.The 11C-L-methionine PET method might be used as a complement to CT or MRI in the evaluation of the effect of proton beam and IFN-alpha treatment in meningiomas. The present attempt failed to demonstrate that the PET tracer 76Br-BrdU could be used for the non-invasive characterisation of growth potential in brain, tumors.
91-554-5034-2 / Link / / 2001

Uppsala universitet Medicin
The principal aim has been to investigate the contemporary role and importance of edible wild plants in the diets of women in different agro-ecological regions of Vietnam. Field studies were undertaken in four villages in the Mekong Delta (MD) and the Central Highlands (CH) in 1995-1999. Data collection included rapid appraisal techniques, botanical identification, dietary assessments (7-day food frequency recall), anthropometry, blood sampling (haemoglobin, serum ferritin, serum retinol and C-reactive protein) and analysis of vegetable samples (dry matter, selected minerals and vitamins, tannins and phytic acid). A food variety analysis was used to test the adequacy of diets.The uses of over 90 wild plant species were documented, many with multiple functions as foods, medicines and livestock feeds. In the dietary assessment 29 species were reported. Most women used a combination of home produced, commercial and wild vegetables. A high 72 and 43% respectively of the vegetables consumed in the MD and CH sites were gathered (rainy season). They contributed significantly to micronutrient intakes, especially vitamin A, calcium, vitamin C and folate. They added considerably to food diversity and women with the most diverse diets had relatively adequate nutrient intakes. The species used and importance of wild plants varied considerably with region, season and ethnicity.The main conclusions are that edible wild plants continue to make important contributions to the nutrient intakes of women. If this is neglected in diet assessments our understanding of the overall dietary adequacy may be misinterpreted and much valuable knowledge of traditional food diversification may be lost. A food variety analysis can be a useful tool in identifying groups with inadequate diets. The dual role of many species as dietary components and in preventive health care deserves greater attention.
91-554-5068-7 / Link / Ogle , Britta M. / 2001

Uppsala universitet Arkeologiämnen
Cultural heritage management in African and in other non-western societies, has mainly been concerned with the preservation and presentation of archaeological monuments primarily from a technical point of view. In Zimbabwe the emphasis has been on the preservation of spectacular monumental architectural places like Great Zimbabwe. Most efforts to preserve and present the archaeological heritage in Southern Africa suffer from a failure to fully understand the significance of the cultural heritage and its value to local communities. Following independence, many Southern African nations realised the value of the past in nation building and the need to restore cultural pride, which had seriously been eroded by colonialism. However, local community interests are often ignored at the expense of international guidelines and frames of operation. Despite the attainment of independence heritage management in Southern Africa assume that local communities are irrelevant to a 'scientific' approach of managing their own heritage.This thesis explores traditional ways of heritage management. They are discussed in relations of the various experiences at the Great Zimbabwe National Monument. The architectural conservation programmes implemented at Great Zimbabwe are outlined and reviewed in the context of archaeological heritage managers in Southern Africa. The thesis emphases the need for integrative planning and management structures that promotes a rapprochement between scientific and local knowledge structures. This provides the best chance of avoiding irreversible cultural degradation resulting from arbitrary decisions of management and policy makers.
91-506-1466-5 / Link / Ndoro , Webber / 2001

Uppsala universitet Fysik
The extreme value statistics of systems possessing a two-hump probability density of the relevant variable, in which the left peak is more pronounced than the right one, is studied. It is shown that systems of this type display a nontrivial transient behavior in the form of anomalous fluctuations around the mean, for certain (finite) ranges of observational time windows. The results are illustrated on independent identically distributed random variables, systems possessing two locally stable states and subjected to additive white noise, and dynamical systems in the regime of deterministic chaos.
N/A / Link / Nicolis , S. C. / 2008

Uppsala universitet Kirurgi
Although two-thirds of colorectal cancer patients are cured by surgery, approximately 50% of the patients with this disease develop locally recurrent or distant metastases during the course of their illness. The aim of this study was to identify metastatic sites associated with poor prognosis in rectal cancer and then to investigate methods that can prevent the development and growth of metastases and optimise uptake of drugs at these sites in animal models.In a defined population, 151 patients with irresectable metastatic or local rectal cancer were identified. Bilateral liver involvement, abnormal liver function tests, paritoneal growth or abdominal lymph node metastases implied a poor prognosis.In a study on Wistar rats with liver metastases from colorectal cancer, blocking of hyaluronan uptake and elimination by the liver enhanced the hyaluronan uptake in liver metastases. Hyaluronan may thus be used to promote uptake of drugs in specific hyaluronan receptor-positive turnout sites.Adjuvant intravenous radioimmunotherapy delivered as a specific or unspecific monoclonal antibody prevented human colonic cancer calls inoculated into the portal vein of nude rats from developing into liver metastases. Furthermore, intraperitoneally administered radioimmunotherapy inhibited the growth of peritoneal metastases.Blocking of 5-FU absorption with a vasoconstrictive agent enhanced the uptake of 5-FU in peritoneal metastases. In addition, the uptake of 5-FU in peritoneal metastases could be improved when these turnouts were mechanically disintegrated by surgical turnout reduction and the drug was given intraperitoneally.
91-554-4912-3 / Link / Mahteme , Haile / 2001

Uppsala universitet Obstetrik Och Kvinnosjukdomar
Studies were conducted in Dar es Salaam, Tanzania to explore the postpartum concerns of mothers and midwives' views on their role in postpartum care. In the first study, 50 primiparas and 50 multiparas sorted cards in their homes two weeks after childbirth. The second study involved a cohort of primiparas in their homes one (n=110) and six weeks (n=83) after delivery. Mothers with a minimum of seven years primary education were sub-divided into two groups: interview then sorting cards (n=47) or sorting cards then interview (n=32). Women with less than seven years of primary education (n=31) were interviewed only. Focus group discussions and grounded theory methods were used in the third study on midwives' views. A total of 49 midwives participated.Primiparas categorized significantly more topics as worries than did multiparas for both baby-related topics, and topics about the mother herself. Both primiparas and multiparas expressed a similar number of family-related topics as worrisome. In the primipara's study, general trends of decreasing worry and increasing interest and confidence for factors related to the baby and to the mother herself were observed from one to six weeks. Trends of increasing worry and decreasing confidence among mothers were observed with respect to family relationships. Midwives also identified that first time and younger mothers need more professional as well as family and social support. Postpartum programmes that consider such issues are useful in addressing the specific needs of mothers.Mothers more often expressed worry and interest during the interview when they had sorted cards first. The order of data collection method did not influence the way women sorted cards.Eight categories emerged from the study of midwives' views: a) reflecting, b) getting ready, c) defining abilities, d) networking, e) integrating, f) balancing, g) dealing with reality, and h) caring. The core category was " becoming a good resource and support person for postpartum woman". The mediating factors were: a) structure and approach in maternal and child health services, b) midwives' knowledge, attitude and skills, c) informal sources of knowledge for parents, and d) cultural beliefs and practices. A theoretical framework was developed. Interventions for midwives should focus on the components of the theoretical framework.
91-554-5067-9 / Link / Lugina , Helen Igobeko / 2001

Uppsala universitet Utvecklingsbiologi
Our ability to map and sequence whole genomes is one of the most important developments in biological science. It will provide us with an unprecedented insight into the genetic background of phenotypic traits, such as disease resistance, reproduction and growth and also makes it feasible to study the processes of genome evolution. The main focus of this thesis has been to develop a linkage map of the horse (Equus caballus) genome. A secondary aim was to expand the number of physically mapped genes in the horse, allowing comparative analyses with data from the human genome map. Finally, attempts were made to identify single nucleotide polymorphisms (SNPs) on the horse Y chromosome.The development of a genome map relies on the information generated by both linkage and cytogenetical studies. To integrate genetical and physical assignments in the very early phase of equine genome map construction, 19 polymorphic microsatellite markers were isolated from lambda phage clones which, in parallel, were physically assigned to chromosomes by fluorescent in situ hybridization (FISH). The microsatellites were simultaneously mapped by linkage analysis in a Swedish reference pedigree.A first primary male autosomal linkage map of the domestic horse was constructed by segregation analysis of 140 genetic markers within eight half-sib families with, in total, 263 offspring. One hundred markers were arranged into 25 linkage groups, 22 of which could be assigned physically to 18 different chromosomes. The total map distance contained within linkage groups was 679 cM. The presented map provides an important framework for future genome mapping in the horse.Our contribution to the comparative horse genome map, was the presentation of map data for 12 novel genes using FISH and somatic cell hybrid mapping. AD chromosomal assignments except one were in agreement with human-horse Zoo-FISH data. The exception concerned the CLU gene which was mapped by synteny to ECA2 while human-horse Zoo-FISH data predicted that it would be located on ECA9.The level of SNPs on the horse Y chromosome was also investigated by DNA sequencing and denaturing high performance liquid chromatography (DHPLC) of Y chromosome-specific fragments derived mainly from BAC clone subcloning. The amount of genetic variability was found to be very low, consistent with low male effective population size.
91-554-5036-9 / Link / Lindgren , Gabriella / 2001

Uppsala universitet Arkeologi, Utomeuropeisk
978-3-11-018387-0 / Link / Ljungkvist , John / 2007

Uppsala universitet Humaniora Och Religionsvetenskap
N/A / Link / Gustafsson Chorell , Torbjörn / 2009

N/A / Link / Lindström , Anna /

Extracranial carotid artery disease, mainly due to atherosclerosis, is a common cause of stroke. The risk for future stroke can be reduced in selected patients by carotid endarterectomy (CEA). Duplex scanning has been increasingly used for diagnosis of carotid artery disease. The aim of this thesis was to assess the role of duplex scanning in the management of carotid artery disease by evaluating various methodological and clinical aspects of its use.Retrospective analysis of 4,548 carotid artery duplex scans demonstrated that different validated spectral Doppler criteria had a significant effect on the proportion of patients receiving a diagnosis of ≥70% internal carotid artery (ICA) stenosis. The Doppler angle of insonation significantly affects velocity measurements and is important in differentiating 50-69% and ≥70% ICA stenosis. Two hundred eighty seven consecutive carotid endarterectomies were analysed retrospectively. The perioperative major stroke/mortality rate was 2.2% in 229 operations with duplex scanning as the sole preoperative imaging modality. Early postoperative duplex scanning was technically feasible and a high ICA flow velocity after CEA was often transient. In 24 patients with spontaneous cervical artery dissections, four pathological flow patterns were identified: absence of flow, reduced flow, staccato flow and stenotic flow.Duplex scanning has important implications in the management of patients with extracranial carotid artery disease. However, duplex performance depends on correct application of the method and selection of appropriate criteria for the definition of disease. Duplex scanning can be reliably used to select patients for CEA. Moreover it is a useful diagnostic modality in the immediate postoperative period. Finally, it can be reliably used for diagnosis of spontaneous cervical artery dissections.
91-554-5004-0 / Link / Logason , Karl / 2001

Uppsala universitet Språkvetenskap
978-91-554-7011-1 / Link / Shahidi , Minoo / 2008

Uppsala universitet Övrigt
This thesis aims to re-think subjectivity in constructive rather than deconstructive terms of disintegration and dismantling. This shift is effected through a reading of Gilles Deleuze that brings together two concepts that are incompatible in his philosophy – immanence and subjectivity – and by my reading of three fictional texts that engage Deleuze in a generative dialogue.Kathy Acker’s novel Great Expectations, David Mack’s graphic novel series Kabuki, and David Lynch’s film Mulholland Drive are all postmodern texts that have been read predominantly as portraying subjectivities as fragmented through strategies of intertextuality, metatextuality, and fragmentation. These texts, I argue, can be seen as positing alternative and more productive subjectivities if approached via the Deleuzean concepts of repetition, univocity, and the event. At the same time, these particular works “speak back” to Deleuze and create some tensions concerning how his concepts may be understood.In Chapter One, I show how Deleuze’s concept of repetition is applicable to but also rethought through Acker’s novel via the more forceful notion of pirating. Pirating, I suggest, can be seen as a textual strategy that employs and builds on repetition to help us re-envisage certain literary traditions of how subjectivity is presented. In Chapter Two I suggest that the concept of univocity makes it possible to envision how a violent inscription of subjectivity can be reconfigured through negotiations of visual and verbal signs. I investigate how Mack’s presentation of faces and masks questions Deleuze’s understanding of the face as a crucial component in the construction of a transcendent subjectivity. In Chapter Three, I discuss aural and visual reconfigurations of Hollywood clichés in Lynch’s film through Deleuze’s concept of the event.The event, as denoting a shift between virtual and actual, enables me to discuss the creative potential opened by the complex temporalities through which the main female characters are portrayed. In sum, alternative and more affirmative subjectivities emerge in the works of Acker, Mack, and Lynch once their textual tensions and slippages are put in a productive exchange with Deleuzean thought.
978-91-506-2089-4 / Link / Beckman , Frida / 2009

Uppsala universitet Fysik
One of the main topics in the modern String Theory are the conjectured string/gauge (AdS/CFT) dualities. Proving such conjectures is extremely difficult since the gauge and string theory perturbative regimes do not overlap. In this perspective, the discovery of infinitely many conserved charges, i.e. the integrability, in the planar AdS/CFT has allowed us to reach immense progresses in understanding and confirming the duality.The first part of this thesis is focused on the gravity side of the AdS5/CFT4 duality: we investigate the quantum integrability of the type IIB superstring on AdS5 x S5. In the pure spinor formulation we analyze the operator algebra by computing the operator product expansion of the Maurer-Cartan currents at the leading order in perturbation theory. With the same approach at one loop order, we show the path-independence of the monodromy matrix which implies the charge conservation law, strongly supporting the quantum integrability of the string sigma-model. We also verify that the Lax pair field strength remains well-defined at one-loop order being free from UV divergences. The same string sigma-model is analyzed in the Green-Schwarz formalism in the near-flat-space (NFS) limit. Such a limit remarkably simplifies the string world-sheet action but still leaving interesting physics. We use the NFS truncation to show the factorization of the world-sheet S-matrix at one-loop order. This property defines a two-dimensional field theory as integrable: it is the manifestation of the higher conserved charges. Hence, we have explicitly checked their presence at quantum level. The second part is dedicated to the AdS4/CFT3 duality: in particular the type IIA superstring on AdS4 x CP3. We compute the leading quantum corrections to the string energies for string configurations with a large but yet finite angular momentum on CP3 and show that they match the conjectured all-loop Bethe Ansatz equations.
978-91-554-7575-8 / Link / Giangreco Marotta Puletti , Valentina / 2009

In the broad-nosed pipefish Syngnathus typhle, brooding males positioned themselves significantly more often towards the warmer part (18 degrees C) of an aquarium. whereas females were indifferent in this respect. This behavioural temperature preference may increase male brooding rate and indirectly influence patterns of mating competition. (c) 2008 The Author Journal compilation (c) 2008 The Fisheries Society of the British Isles.
N/A / Link / Ahnesjö , Ingrid / 2008

Uppsala universitet Humaniora Och Religionsvetenskap
N/A / Link / Packalén , Malgorzata Anna / 2008

Uppsala universitet Ekonomi
N/A / Link / Lundström , Catrin / 2008

Uppsala universitet Övrigt
N/A / Link / Abdsaleh , Shahin /

Uppsala universitet Klinisk Genetik
Angiogenesis is the formation of new blood vessels from pre-existing ones. New blood vessel formation is fundamental in processes such as reproduction, embryonic development and wound healing. Growth of neoplasms is accompanied by increased angiogenesis. This thesis describes cellular and molecular mechanisms of importance for angiogenesis. The effects of a number of different anti-angiogenic substances on tumor growth were investigated.Fibroblast growth factor-2 (FGF-2) is involved in different processes in angiogenesis. We have shown that Crk, an adaptor protein, participates in signaling downstream of FGF receptor-1, via the juxtamembrane tyrosine residue 463. Signal transduction through FGF receptor-1 and Crk regulates endothelial cell proliferation.Anti-angiogenic effects of endostatin, latent antithrombin and prelatent antithrombin were evaluated. We found that FGF-2- and vascular endothelial growth factor (VEGF)- induced angiogenesis in the chick chorioallantoic membrane assay is inhibited by these anti-angiogenic substances, which also efficiently reduce tumor growth in mice.Molecular mechanisms underlying the anti-angiogenic effects were investigated and endostatin was found to mediate its activity through induction of a 125 kDa kinase, leading to apoptosis. Endostatin was shown to be dependent on heparin/heparan sulfate binding for angiogenesis inhibition only in FGF-2- stimulated vessels, and not in those stimulated with VEGF. A peptide encompassing residues 180-199 in endostatin, capable of mimicking the effects of endostatin on endothelial cells was identified. Latent antithrombin and prelatent antithrornbin were found to exert their anti-angiogenic effects through negative regulation of focal adhesion kinase and focal adhesion formation.
91-554-4954-9 / Link / Larsson , Helena / 2001

We study a scheme for electrical detection, using electron spin resonance, of coherent vibrations in a molecular single electron level trapped near a conduction channel. Both equilibrium spin currents and non-equilibrium spin and charge currents are investigated. Inelastic side-band antiresonances corresponding to the vibrational modes appear in the electron spin resonance spectrum.
N/A / Link / Fransson , J. / 2008

N/A / Link / Kuusk , Sandra /

Uppsala universitet Nordiska Språk
N/A / Link / Elmevik , Lennart / 2003

Uppsala universitet Övrigt
N/A / Link / Marcusson , Lena / 2008

Uppsala universitet Obstetrik Och Kvinnosjukdomar
Hyaluronan is an important component of the lung extracellular matrix, with a high capacity for water immobilization, but information on perinatal changes in the lung hyaluronan concentration and their association with changes in the lung water content is limited.In this study, conducted both in rabbit pups and in human infants, we investigated changes in the hyaluronan concentration and distribution in the lung and in the lung water content after preterm or term birth, and changes produced by common antenatal and postnatal pathological conditions and treatments.In rabbit pups, we found a gradual decrease in lung hyaluronan concentration and in the intensity of alveolar hyaluronan staining with advancing gestational age at birth in late gestation, but no further changes during the first 7-9 days of life. The lung water content was uniformly high before birth, but decreased significantly after preterm delivery or at birth at term.Postnatal exposure of newborn preterm or term rabbit pups to hyperoxia for 4-9 days resulted in an increase in both lung hyaluronan concentration and lung water content. This was accompanied by more intense hyaluronan staining, mainly in the alveolar walls.Antenatal exposure of rabbit pups to betamethasone or terbutaline resulted in a lower lung hyaluronan concentration at preterm birth, associated with less intense hyaluronan staining in alveolar walls, without altering the lung water content. Betamethasone exposure had a maximal effect at 25 days of gestation (term = 31 days), decreasing thereafter with advancing gestation, while terbutaline exposure resulted in a gradually increasing effect during late gestation, with a maximum at 29 days.In deceased infants born at a gestational age of < 32 weeks, the lung hyaluronan concentration at death was most strongly associated with the gestational age at birth. It also covaried with sex, antenatal steroid administration, intrauterine bleeding, mode of delivery, birth weight, IRDS, and surfactant treatment. In infants born at a gestational age of> 33 weeks there was a weaker association between lung hyaluronan concentration and gestational age. In this group, the lung hyaluronan concentration was associated with administration of a high concentration of oxygen, and covaried with maximal ventilatory pressure, and lung water content.
91-554-4989-1 / Link / Johnsson , Hans / 2001

The aim of the study was to examine the immune response and different immunoprotective strategies in experimental type 1 diabetes mellitus. The autoimmune destruction of the insulin-producing pancreatic β-cells that leads to type 1 diabetes is complex and incompletely understood. Activated immune cells infiltrate the pancreatic islets at an early stage of the disease, and they produce and release cytokines, which may contribute to β-cell dysfunction and death.Several immunomodulatory agents with different mechanisms have recently been developed in order to suppress cytokine function such as MDL 201, 449A, a novel transcriptional inhibitor of TNF-α. At least in rodent β-cells, many of the toxic actions of cytokines depend on the synthesis of nitric oxide (NO). Aminoguanidine (AG), an inhibitor of NO formation, might therefore be an interesting compound for prevention of type 1 diabetes. Another substance that could influence the course of events leading to this disease is the pituitary hormone prolactin (PRL), since it has the ability to activate different immune cells. We have studied the effects of AG, PRL and MDL 201, 449A on the development of hyperglycaemia and pancreatic insulitis in multiple low dose streptozotocin induced autoimmune diabetes in mice. The natural course after syngeneic islet transplantation of pancreatic islets in NOD mice, a model of type 1 diabetes mellitus was also investigated. AG and PRL were also studied in vitro on cultured isolated rodent pancreatic islets.We suggest that the insulin-producing cells are specifically targeted by the inflammatory response after syngeneic islet transplantation in type 1 diabetic mice. Our data do not exclude a role for NO in type 1 diabetes, but it raises concerns about the use of AG as a therapeutic agent since an increased mortality and no decline in diabetes frequency was observed. AG did not seem to be directly harmful to β-cell function, but it could affect pancreatic and islet blood flows. PRL and MDL 201, 449A could both counteract hyperglycaemia and insulitis in the early phase of autoimmune diabetes.
91-554-4972-7 / Link / Holstad , Maria / 2001