Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Investigation into the molecular basis of diabetes-induced erectile dysfunction was carried out on corpus cavernosum tissue from control and streptozotocin (STZ)-induced diabetic rats. Increased expression of endothelial nitric oxide synthase (eNOS) and increased nitrosative stress was found in the diabetic penile tissue. Diabetic neuropathy is associated with a failure in axonal regeneration. <i>In vitro</i> axon growth, guidance and regeneration model systems were used to study both the intrinsic nature of diabetic DRG neurones to grow and respond to guidance cues, but also to study the supportive properties of the diabetic nerve environment for axon regeneration. Cyclic Adenosine-3’5-Monophosphate (cAMP) signalling is compromised in diabetic DRG neurones. Increasing cAMP in diabetic neurones reduced the deficit in neurite growth and reversed the aberrant response of diabetic neuronal growth cones to the cAMP-dependent trophic factor, nerve growth factor (NGF). Diabetic neurones display reduced expression of Exchange protein activated by cAMP (Epac), a downstream effector of cAMP. Specifically activating Epac also rescued the abnormal turning responses of diabetic DRG neurones. Impaired axonal regeneration in diabetes has been, in part, attributed to delayed Wallerian degeneration. Using the cryoculture bioassay, it was shown that during regeneration the peripheral nerve environment, of both control and diabetic rats are equally supportive for axon growth. In summary, this is the first study to imply that specific signalling mechanisms, involving the cAMP-Epac pathway, may be compromised in neurones from diabetic rats, which contribute towards reduced neurite growth and abnormal responses to axon guidance cues.

Thesis (Ph.D)--Freien Universität Berlin, 2008.

Neuropathy is a major complication that affects nearly half of all patients with diabetes, greatly decreasing their quality of life. Patients experience a wide range of symptoms including pain, numbness, weakness and other morbidities. While its pathogenesis has been the focus of extensive research, there are still few effective treatment options available for this disease. The discovery of novel molecular targets underlying this diabetic neuropathy may lead to the development of new, more effective therapeutics. DLC2, a Rho GTPase-activating protein with specific activity for RhoA, was shown to be involved in pain signaling. Mice deficient for this protein (DLC2-/-) have increased RhoA activity in their peripheral nerves, and have heightened pain responses compared to wild type (DLC2+/+) in acute pain tests, displaying increased sensitivity to noxious thermal and inflammatory stimuli. DLC2-/- mice also show elevated blood glucose levels, lower body weight and increased sensitivity to blood glucose compared to wild type. Because of the hyperalgesia to acute pain displayed by DLC2-/- mice compared to wild type, and since the RhoA pathway is known to be involved in the pathogeneses and maintenance of diabetes and its complications, these mice were used to investigate more clinically relevant, chronic pain in a model of diabetic neuropathy. Streptozotocin (STZ), given in multiple low doses over five days (MLDS treatment), was used to induce diabetes in DLC2+/+ and DLC2-/- mice, and their pain responses were tested 8 weeks later. Diabetic DLC2-/- mice (DLC2-/--STZ) were hyperalgesic to thermal stimuli from the hot plate test compared to diabetic DLC2 wild type mice (DLC2+/+-STZ) and vehicle-treated controls of both genotypes (DLC2-/--Veh and DLC2+/+-Veh. Similar responses were seen from the von Frey filament test, where the DLC2-/--STZ group exhibited mechanical allodynia compared to the DLC2+/+-STZ group and both control groups. Dorsal root ganglia (DRG) were dissected from these four groups of mice for qPCR screening and protein analysis. DLC2-/--STZ mice showed significantly higher gene expression of the voltage-gated sodium channel Nav 1.9 compared to DLC2+/+-STZ mice, while there was a strong trend of increased levels in the DLC2-/--STZ group compared to both non-diabetic groups. Western blot analysis of the DRG from these mice shows increased levels of COX-2 expression of DLC2-/--STZ mice compared to DLC2+/+-Veh, and elevated levels of phosphorylated ERK (pERK) in DLC2-/--Veh and both diabetic groups compared to DLC2+/+-Veh. Overall, diabetic DLC2-/- mice have more severe painful diabetic neuropathy, with thermal hyperalgesia and mechanical allodynia. Increased RhoA activity and pERK, which are known to be involved in regulation, transcription and trafficking of sodium channels, may lead to increased Nav1.9 mRNA levels and activation. Localized mainly to nociceptors of the DRG, Nav1.9 is known to play a role in sensitizing neurons through lowering the threshold for action potentials, possibly leading to the observed heightened pain response. Additionally, elevated COX-2 levels in DLC2-/--STZ mice may lead to further deficits through activation of inflammatory responses. Future studies will further investigate how these mechanisms are involved in the altered pain response from diabetes. / published_or_final_version / Anatomy / Master / Master of Philosophy

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser + 4 appendix.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 116-154).

Thesis (M.Sc.)--York University, 2005. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11734

During a surveillance programme all the known diabetics (1150) were identified from a general population of 97,034 representing all patients registered with 10 general practices. A control group of 751 non-diabetic subjects were also drawn from the same general population. A single observer reviewed 1077 (93.6%) of the diabetics and 480 (69%) of the controls. Peripheral vascular disease was detected using doppler ankle/brachial pressure index in 20.6% (95% CI 18.2-23.0) of diabetics and 9.6% (95% CI 7.0-11.2) of controls. There was no significant difference between the prevalence in non-insulin dependent and insulin dependent diabetics after adjusting for age. The prevalence in either type of diabetes was however significantly greater than in controls. Multiple logistic regression analysis revealed that age, cerebrovascular disease, coronary artery disease, mean systolic blood pressure, blood glucose, proteinuria and serum cholesterol were significantly and independently associated with the presence of peripheral vascular disease in diabetics. Body mass index was inversely associated. For controls only age and smoking were found to be significant variables. Neuropathy determined by clinical evaluation and sensory vibration thresholds was found in 16.8% (95% CI 14.6-19.0) of diabetics and 2.9% (95% CI 1.4-4.3) of controls (p<O.001). There was however no significant difference between insulin dependent and non-insulin dependent diabetics after accounting for age. Alcohol intake, age, height, HbAl, foot deformity and the presence of any retinopathy were significantly associated with neuropathy in diabetics and only male sex, age and foot deformity in controls. Past or present foot ulceration occurred in 7.4% (95% CI 5.8-9.0) of diabetics and 2.5% (95% CI 1.1-3.9) of controls (p<O.00l). Amputation was found in 1.4% (95% CI 0.7-2.1) of diabetics but in no controls. Using logistic regression analysis ulceration was significantly associated with duration of diabetes, foot deformity, absent light touch, impaired pain perception, an absent dorsalis pedis pulse and the presence of any retinopathy. For controls only absent light touch was significant. Using a stepwise multiple regression only age and duration of diabetes were significantly associated with the presence of amputation.

背景：腕管綜合征，又名腕管狹窄征，俗稱“滑鼠手＂，是最常見的周圍神經卡壓性疾患，有研究顯示，腕管綜合征的發病率正在逐年的上升，在壽命為70歲以下的人群中發生腕管綜合征的概率女性為l1%、男性為3.5%。是一種因為正中神經在腕管內因為腕管內的容積減少或壓力增大而受到壓迫，引起的手指麻木無力的戚覺，運動和自主功能紊亂症候群。 目的：通過查閱有關中醫治療腕管綜合征文獻，歸納和總結正確的合理的治療思維，尋找出理想的治療腕管綜合征的方法。 方法：1.檢索近20年的相關文獻，輸入關鍵字“腕管綜合征 針灸 推拿 中藥 Carpal Tunnel Syndrome＂，在CNKI資料庫和EBSCOhost資料庫和維普資料庫中，根據納入標準：(1）診斷為腕管綜合征（2）以中醫為主治療之文獻。排除標準：非中醫治療文獻，選出共57篇符合納入標準的文獻，並用Excel軟體對其記錄和總結。 2. 臨床隨診塗封老師從2015年1月到2015年4月期間在相關浸會大學診所收集診斷為腕管綜合征的患者，觀察針灸、中藥和推拿治療此病的效果。 結果：針灸治療腕管綜合征的最常用的幾個穴位，分別為內關、大陵、外關、合谷、陽池、陽溪。中藥最常用的幾味藥為桂枝、威靈仙、透骨草、川穹、伸筋草、紅花、當歸。在中藥熏洗方面，最常用的是透骨草、伸筋草、威靈仙、桂枝。在中藥外敷方面，最常用的是桂枝、威靈仙、防風、透骨草。在中藥內服方面，最常用的是當歸、乳香、桂枝、雞血藤。在手法治療治療腕管綜合征，主要是以放鬆肌肉和松解組織粘連的手法為主。中醫方法治療腕管綜合征的效果，要優於現代醫學治療此病的效果。

published_or_final_version / Molecular Biology / Master / Master of Philosophy