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Phenotypic modulation of vascular smooth muscle in organ culture

Contraction of blood vessels for the regulation of blood flow and pressure is dependent on vascular smooth muscle cells (VSMC) located in the medial layer of the vascular wall. Adult, differentiated VSMC have a well developed contractile system and a low rate of proliferation. Under the influence of hormones, growth factors, inflammatory mediators and tissue factors, cells may modulate to a ”synth

PACAP and orphanin FQ/nociceptin -Distribution, importance and regulation in sensory neurons and spinal cord

Neuropeptide expression in the nervous system is abundant and plastic, and an altered expression after injury is an example of a functional response, helping the neuron to cope with adverse changes, and involves effects on differentiation, synthesis, repair/regeneration, survival, and modulation of signal transmission. I have investigated the distribution/expression of the neuropeptides, orphanin

Phase Transitions in Large Oscillator Lattices

This thesis deals with large networks of limit cycle oscillators. A limit cycle oscillator is a dynamical system that has a periodic attractor in phase space, and is defined in continuous time. To each such oscillator one can associate a natural frequency. Virtually all biological systems that show periodic oscillations can be seen as limit cycle oscillators. The same is true for oscillating mecha

Poly(Lactide-co-Glycolide) in Controlled-Release Pharmaceuticals - Release Mechanisms

Controlled-release formulations reduce the frequency of injections and better maintain plasma concentrations within the therapeutic window. Poly(D,L-lactide-co-glycolide) (PLG) is currently the most frequently used biodegradable polymer for this application. In order to be able to control the release rate, it is vital to know the underlying release mechanisms. A novel method for measuring the diff

Dietary fat as an exposure in epidemiological studies. Observations in the Malmö Diet and Cancer cohort

The aim was to explore the inherent meaning of total fat and to examine the associations between relative fat intake and postmenopausal breast cancer. Furthermore, the impacts of the alterations in dietary assessment routines are discussed. This thesis uses data from the Malmö Diet and Cancer study, a prospective cohort study. Information on dietary habits, lifestyle, and socioeconomic factors wa

Sexual conflict and selection on pistil and pollen traits

The incidence of sexual selection in plants is today acknowledged, however, just as in animals, evolution and maintenance of mate choice is gravely underexplored. Moreover, the potential for sexual conflicts to occur in plants has only been assessed empirically to a very limited degree. Using the hermaphroditic annual herb Collinsia heterophylla, I looked deeper into the role of pollen-pollen comp

Pharmacokinetics of the enantiomers of thalidomide

Thalidomide has a chiral center and the racemate of (+)-(R) and (-)-(S)-thalidomide was introduced as a hypnotic/sedative drug in 1957. In 1961 it was withdrawn due to teratogenicity and neuropathy. There is a growing interest in thalidomide treatment of immunomodulatory diseases. Given this renewed interest the aim of this thesis was to achieve a more rational use of thalidomide. Therefore some c

Skin hydration - How water and osmolytes influence biophysical properties of stratum corneum

The outermost layer of skin (i.e., the stratum corneum, SC) is the interface that separates the water-rich inside of the body from the relatively dry external environment. SC forms an effective permeability barrier, which has to be overcome in transdermal drug delivery. Its function as a barrier for molecular diffusion depends on the SC molecular structure and phase behavior. Both structure and ph

Structure and function of the cytoskeleton in cardiac and skeletal muscle

We have examined the functional and structural roles of the cytoskeletal protein desmin in cardiac and skeletal muscles using a genetically modified mouse (Des-/-) with the desmin gene ablated. Desmin forms filaments at the Z-disks in the striated muscle sarcomere, have connections to the sarcolemma and most likely align sarcomeres and whole cells. We have shown a decreased contractile function of

Spinal Cord Processing of Sensory Information: Spatial Organization and Adaptive Mechanisms.

Principles for sensorimotor transformation and plasticity in the spinal cord and functional repair in the root-avulsed spinal cord were studied. A comparative study confirmed that the nociceptive withdrawal reflex (NWR) system is composed of reflex modules, with each performing a finely tuned transformation of skin sensory input to activity in one muscle. This suggests that modularity of the NWR s

Clinical curse, predictive factors and effects of intervention after attempted suicide. A randomised controlled study

Abstract One important task for the mental health services is to prevent suicidal behaviour, especially among persons at high risk, e.g. those who have attempted suicide. In two follow-up samples, one and three months after a suicide attempts, both n=97, we found that 32% and 38% of the patients respectively had no treatment and 30% in each sample had suicidal thoughts. In a randomised controlled

The role of leucine-rich repeat glycoproteins/proteoglycans in the assembly of collagen matrices

The properties of different connective tissues depend on the synthesis and assembly of macromolecular structures composed of collagen and other extracellular matrix components. Mechanisms modulating these events play important roles in the formation of a functional tissue. We have studied the role of collagen-binding extracellular matrix leucine-rich repeat glycoproteins/proteoglycans in the forma

Posture and brain function in dementia. A study with special reference to orthostatic hypotension.

Orthostatic hypotension (OH) is believed to be an important cause of cerebral hypoperfusion, leading to chronic fatigue, blurred vision, unsteadiness, dizziness and sometimes syncope. It may also result in episodes of confusion, falls and fractures. The coupling between OH and organic dementia is not clear. Our findings in a large group of patients with Alzheimer's disease, vascular- and frontotem

On the role of the retinoblastoma tumor suppressor gene in hematopoietic differentiation

The aim of this study was to investigate the role of some tumor suppressor gene products (with emphasis on the retinoblastoma suppressor gene product) in the regulation of differentiation and proliferation in leukemic and normal hematopoietic cells. For this purpose, the expression of the tumor suppressor genes RB, p53 and p16 were artificially altered. Cells used were human leukemic cell lines an

Endothelial function during ischemia-reperfusion and effects of inhalation of nitric oxide

The vascular endothelium is an important regulatory organ in circulatory physiology and plays a central role in the response to acute inflammation and ischemia/reperfusion. Activation and dysfunction of the pulmonary vascular endothelium are closely related to clinical findings of pulmonary dysfunction. The endothelial-derived relaxing factor, nitric oxide (NO), is a gas, which can be administered

Regulation of lymphocyte activation and death

T lymohocytes (T cells) and B lymphocytes (B cells) are important effector cells of the adaptive immune system. In response to infections, B cells are activated and produce antibodies against specific antigens. There are two types of T cells, cytotoxic T cells that kill cells infected with bacteria or viruses, and helper T (Th) cells that help B cells produce antibodies by secreting cytokines as w

Altered expression of contractile endothelin receptors in the vascular bed

This thesis aims at characterizing the endothelin (ET) receptors in different vascular beds of man and rat. The ET-A receptor was shown to be the only contractile ET receptor present in all vascular regions, with the exception of the rat mesenteric vein where a weak ET-B receptor-mediated contraction was seen. Treatment with antisense oligodeoxynucleotides to the ET-A receptor mRNA during organ cu

Postnatal Development of Spinal Nociceptive Pathways: Evidence for Involvement of Experience-Dependent Mechanisms

The adult organization and postnatal development of the nociceptive withdrawal reflexes (NWR) of single hindlimb muscles were examined in decerebrate spinal rats using electromyography. In adult rats, NWR were found to perform highly organized sensorimotor transformations, with single muscles receiving excitatory cutaneous input from specific receptive fields (RF) whose distribution of sensitivity

β-Mannan degradation by gut bacteria - Characterization of β-mannanases from families GH5 and GH26

The human gut flora is important for our well-being. The gut bacteria are able to degrade and metabolize complex carbohydrates. Examples of such carbohydrates are β-mannans. β-Mannans consist of a backbone of β-1,4-linked mannose units and are present in e.g. the endosperm of legumes such as guar or carob. The composition of the β-mannan varies with the plant source. Carob and guar β-mannans are s