Inaug.-diss.-Bern. / "Sonder-abdruck aus dem Archiv für wissensch. u. prakt. thierheilkunde.-bd. 28. H. 5 u. 6. 1902." "Litteratur": p. 86-96.

Inaug.-diss.--Bern. / "Literatur": p. [69]-70.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 110-116).

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

While premature birth is still one of the major clinical problems worldwide, the exact physiological mechanisms underlying myometrium activity during pregnancy remain unclear. In this thesis, a novel biophysically detailed model was constructed using available experimental data to simulate chemical, electrical and mechanical activity in a late pregnant rat uterine myocycte. The developed model has been used to elucidate the ionic mechanism underlying myometrium functionality, providing better insights in the function of the uterus during pregnancy. The model consisted of 15 membrane currents, intracellular calcium handling process coupled with a sliding actin-myosin filament mechanical model to describe uterine behaviour and contractile activity at the single myocyte level. Each of the ionic currents were modelled using Hodgkin-Huxley-type equations. The simulated current traces and current-voltage curves were validated with experimental recordings and the model was further validated by the ability to produce a bursting action potential (AP) during an external stimulus. The model replicated the effects of estradiol during pregnancy, modulating the amplitude and activation properties of individual Ca2+ and K+ currents, therefore altering the AP configuration to a tonic-like plateau. The model also reproduced the actions of drugs to inhibit certain channels to investigate their roles in myometrium. Sensitivity analysis was performed to examine the model's behaviour to changing parameters. A simple 1-D study was conducted to investigate how electrical signals propagate along strand of cells. Although the model successfully replicated results similar to recordings seen in the experiments, limitations have to be addressed and more studies have to be carried out to further improve the model.

No description available.

Endometriosis is a chronic estrogen-dependent gynecological disease where endometrial cells implant at inappropriate sites causing significant pelvic pain, decreased quality of life, and often infertility. It affects 10% of women of reproductive age, and there is no minimally invasive diagnostic test. Consequently the time to diagnosis, which occurs during laparoscopic surgery followed by pathological confirmation of disease, is prolonged and exceeds 11 years. During this time, the disease often worsens and women thus experience avoidable morbidity. Additionally, endometriosis is a financial burden on the healthcare system; its annual cost was $69.4 billion (U.S.) and $1.8 billion (Canada) in 2009. For these reasons, identifying a clinical marker remains a top priority. Although multiple putative markers have been identified and reviewed, emerging evidence suggests a relationship between neurotrophins and endometriosis. The neurotrophins are growth factors recognized for promoting neuronal differentiation, growth, and maintenance. Recently, they have been shown to induce pathways central to endometriosis including proliferation, adhesion, angiogenesis and resistance to apoptosis, in cultured neurons, epithelial cells, fibroblasts, and cancer cell lines. Although two studies have suggested elevated concentrations of brain-derived neurotrophic factor (BDNF) in the plasma and eutopic endometrium of women with endometriosis, relatively little is known about uterine BDNF. Herein, we demonstrate the conservation of BDNF and its high affinity receptor in the mammalian uterus, and show the upregulation of BDNF and its low affinity receptor by estradiol in the mouse uterus. Encouraged by our results, we assessed circulating BDNF for its ability to differentiate between women with and without endometriosis, as excess estradiol in endometriotic lesions might increase BDNF in women with disease. Our results revealed that circulating BDNF concentrations were significantly higher in women with endometriosis, particularly those with Stage I and II disease compared to controls. Furthermore, women with endometriosis undergoing ovarian suppression had significantly lower circulating BDNF than women not undergoing treatment, suggesting that BDNF may provide an opportunity to monitor patient response to treatment. Taken together, the data herein advances our limited knowledge of uterine neurotrophins, and supports a link between BDNF and endometriosis. I therefore strongly suggest that BDNF is a useful clinical marker of endometriosis, and encourage additional research to determine its role in the pathophysiology of disease. / Thesis / Doctor of Philosophy (PhD) / Endometriosis is a chronic condition that affects over 10% of women of reproductive age. Women with endometriosis suffer from debilitating pelvic pain and it takes approximately 12 years before they are diagnosed during surgery. This is in part because there is no blood test to diagnose disease. We are interested in using a protein called brain-derived neurotrophic factor (BDNF) that is linked to several of the pathways that are disturbed in women with endometriosis as a means of determining whether or not a woman has endometriosis. The key goals of this thesis are to show that BDNF is a protein which is found in the uterus of many species, that it is controlled by estrogen, and that it might be useful in diagnosing endometriosis and monitoring how well a patient is responding to endometriosis treatment.

No description available.

No description available.