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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
81

INVESTIGATING THE ROLE OF MANF & CDNF IN THE PATHOPHYSIOLOGY OF PARKINSON’S DISEASE / INVESTIGATING THE ROLE OF CEREBRAL DOPAMINE NEUROTROPHIC FACTOR (CDNF) & MESENCEPHALIC ASTROCYTE-DERIVED NEUROTROPHIC FACTOR (MANF) IN THE PATHOPHYSIOLOGY OF PARKINSON’S DISEASE

Shawaf, Omar January 2017 (has links)
CDNF and MANF are members of a recently discovered and evolutionarily conserved neurotrophic factor family implicated in supporting the survival and protection of midbrain dopaminergic neurons in the nigrostriatal pathway, which degenerate in Parkinson’s Disease (PD). Increasing evidence demonstrated that MANF overexpression resulted in significant protection and repair of TH+ cells and DA neurons in the substantia nigra (SN). In addition, continuous infusion of CDNF demonstrated greater protection of TH-positive neurons in the SNc and fibers in striatum than GDNF in the 6-OHDA neurotoxin model. Current literature suggests that CDNF and MANF are involved in regulating ER stress and are upregulated in vitro and in vivo during the unfolded protein response (UPR). Thus, this study sought to investigate whether selective knockdown (K/D) of MANF and CDNF causes pathophysiological conditions that lead to the behavioural manifestation of PD in preclinical models. Male Sprague-Dawley rats underwent stereotaxic surgery, whereby 2 μL at 0.5 μL/minute of MANF, CDNF, MANF and CDNF combined, or a scrambled negative control (N=44) of rat lentiviral-mediated shRNA formulations were infused into the SN in reference to bregma: Anterior/Posterior=-5.3 mm, Medial/Lateral=±2.3 mm, Dorsal/Ventral=-7.8 mm. Rats were tested on a battery of behavioural tests for the assessment of PD phenotypes, such as impairments in balance, gait and motor coordination. MANF K/D rats demonstrated PD phenotypes in the rearing duration, beam traversal, rotarod and cylinder test (P <0.05). These results were largely mirrored in the combined MANF and CDNF K/D group, however, CDNF K/D rats failed to demonstrate consistent motor deficits (P >0.05). Additionally, CDNF mRNA expression from the platelets of PD patients revealed no significant differences compared to healthy controls (P >0.05). In conclusion, the etiology of PD remains to be elucidated, and this is the first study to demonstrate that MANF K/D rats recapitulate key motor features of parkinsonism. / Thesis / Master of Science (MSc) / CDNF and MANF are members of a recently discovered and evolutionarily conserved neurotrophic factor family implicated in supporting the survival and protection of midbrain dopaminergic neurons in the nigrostriatal pathway, which degenerate in Parkinson’s Disease (PD). Increasing evidence demonstrated that MANF overexpression resulted in significant protection and repair of DA neurons in the substantia nigra (SN). Current literature suggests that CDNF and MANF are involved in regulating ER stress and are upregulated in cells and in rodents during the unfolded protein response (UPR). Thus, this study sought to investigate whether selective knockdown (K/D) of MANF and CDNF causes the underlying changes in the brain that lead to the behavioural manifestation of PD in preclinical models. 2 μL at 0.5 μL/minute of MANF, CDNF, MANF and CDNF combined, or a scrambled negative control (N=44) of rat lentiviral-mediated shRNA formulations were infused into the SN. Rats were tested on a battery of behavioural tests for the assessment of PD phenotypes, such as impairments in balance, gait and motor coordination. MANF K/D rats demonstrated PD phenotypes in the rearing duration, beam traversal, rotarod and cylinder test (P <0.05). These results were largely mirrored in the combined MANF and CDNF K/D group, however, CDNF K/D rats failed to demonstrate consistent motor deficits (P >0.05). Additionally, CDNF mRNA expression from the platelets of PD patients revealed no significant differences compared to healthy controls (P >0.05). In conclusion, the etiology of PD remains to be elucidated, and this is the first study to demonstrate that MANF K/D rats recapitulate key motor features of parkinsonism.
82

Using Team-Based Learning in Teaching Undergraduate Pathophysiology for Nurses

Middleton-Green, Laura, Ashelford, Sarah L. January 2013 (has links)
No / This paper describes the development, implementation and evaluation of Team-Based Learning (TBL) in a third year undergraduate nursing module.
83

A Combined In Vivo and In Vitro Approach to the Study of Endotoxemia in Swine

Smedley, Jeremy Vance 12 July 2000 (has links)
The cardiopulmonary effects of endotoxin administration (1 microgram/kg) were evaluated in 8-10 week old SPF-derived Yorkshire pigs, both because endotoxemia is a common and important swine problem, and because the pig is a good model for human adult respiratory distress syndrome. Physiological changes included sustained increases in mean pulmonary artery pressure, pulmonary vascular resistance, pulmonary arterial wedge pressure, heart rate, hematocrit, and the arterial partial pressure of carbon dioxide. Transient increases were also observed in central venous pressure and airway pressure. Transient increases, followed by decreases, were observed in mean systemic arterial pressures and systemic vascular resistance. Decreases were seen in cardiac output, cardiac index, arterial partial pressure of oxygen and oxygen saturation. The number of circulating leukocytes, lymphocytes and segmented neutrophils decreased with endotoxin infusion. To investigate the role of airway smooth muscle, bronchial rings were isolated and exposed to contractile agents in tissue baths. A hyperresponsiveness of the third generation bronchi to substance P, carbachol, bradykinin and electric field stimulation was observed. However the increase in response to bradykinin and electric field stimulation were not statistically significant. Histopathology of the lungs demonstrated congestion, hemorrhage and neutrophilic infiltration. / Master of Science
84

An investigation of the importance of the ATM protein in the endothelium and its role in the signalling pathways of NO production

Collop, Natalie Chantel 04 1900 (has links)
Thesis (MScMedSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Ataxia telangiectasia (AT) is a well-characterized neurodegenerative disease resulting from a genetic defect in the Atm gene causing an absence or very low expression of the ATM protein. As AT patients are prone to the development of insulin resistance and atherosclerosis, the aim or the current study was to investigate the importance of the ATM protein in the endothelium and its role in the signalling pathways of nitric oxide (NO) production. To accomplish this, the first objective was to establish an in-house endothelial cell isolation technique harvested from normal and insulin resistant animals. Unfortunately, these cultures, although staining positive with an endothelial cell specific stain, were not pure enough and did not express endothelial NO synthase (eNOS), the central enzyme in NO production. The remainder of the study utilized commercial aortic endothelial cells (AECs) and found that there was a significant increase in NO production when the ATM protein was inhibited by the specific inhibitor, Ku-60019. The beneficial impact of increased NO production includes maintaining vascular homeostasis, promoting angiogenesis, initiating DNA repair by activating p53 and inhibiting smooth muscle cell proliferation. On the other hand, reactive oxygen species (ROS) and reactive nitrogen species (RNS) also generated by high levels of NO, can exert both protective and harmful effects. Examples of these include cell death due to high concentrations of ROS. However, Ku-60019 did not result in increased cell death of AECs. We demonstrated for the first time, a relationship between endothelial ATM protein kinase and the generation of NO. The signalling pathways involved in NO production and glucose utilization form a network of interrelationships. Central to both pathways is the activity of two protein kinases, PKB/Akt and AMPK. Both these kinases are known to phosphorylate the eNOS enzyme to produce NO on the one hand and AS160 to induce GLUT 4 translocation and glucose uptake on the other hand. Activation of the ATM protein is postulated to be a prerequisite for PKB/Akt activation and it may also result in activation of AMPK. However, using insulin to stimulate ATM, we could not show that inhibition of ATM in endothelial cells affected expression or insulin-stimulated activation of PKB/Akt while the PI3-K inhibitor wortmannin, inhibited the latter. In addition, inhibition of ATM negatively regulated the phospho/total ratio of AMPK. We therefore postulate that the NO production elicited by inhibition of ATM, may not be as result of eNOS activity. A second important observation was that inhibition of ATM significantly enhanced phosphorylation of the p85 regulatory subunit of PI3-K. This would imply that ATM normally has an inhibitory effect on p85 phosphorylation and therefore PI3-K activation. We base this assumption on previous publications showing that Ku-60019 does not inhibit PI3K. This again indicates that ATM has a hitherto unexplored regulatory role in endothelial function. / AFRIKAANSE OPSOMMING: Ataxia telangiectasia (AT) is a goed-gekarakteriseerde neurodegeneratiewe siekte a.g.v. ‘n genetiese afwyking in the Atm geen wat lei tot ‘n afwesige of lae uitdrukking van die ATM proteïen. Aangesien AT pasiënte geneig is om insulienweerstandigheid en aterosklerose te ontwikkel, was die doel van hierdie studie om die belang van die ATM proteïen in die endoteel, en sy rol in die seintransduksiepaaie betrokke by stikstofoksied (NO) produksie, te ondersoek. Om dit te bereik, was die eerste mikpunt om ‘n eie endoteelsel isolasie-tegniek (ge-oes van normale en insulienweerstandige diere) te vestig. Ongelukkig was hierdie selkulture nie suiwer genoeg nie.Ten spyte daarvan dat hulle positief getoets het met ‘n endoteelsel-spesifieke kleurstof kon geen uitdrukking van eNOS, die sentrale ensiem verantwoordelik vir NO produksie, waargeneem word nie. Die res van die studie het van kommersiële aorta endoteelselle (AES) gebruik gemaak, en daar is gevind dat die inhibisie van die ATM proteïen met die spesifieke inhibitor, Ku-60019, tot ‘n beduidende toename in NO produksie gelei het. Die voordelige impak van verhoogde NO produksie sluit die handhawing van vaskulêre homeostase, bevordering van angiogenese, inisiëring van DNA herstel deur p53 aktivering en inhibisie van gladdespiersel proliferasie in. Reaktiewe suurstofspesies (ROS) en reaktiewe stikstofspesies (RNS) wat ook a.g.v.verhoogde NO gegenereer word, kan egter beide beskermende sowel as skadelike effekte uitoefen. Voorbeelde sluit seldood a.g.v. hoë ROS konsentrasies in. Ku-60019 het egter nie tot ‘n toename in seldood van die AES gelei nie. Hierdie studie het vir die eerste keer aangetoon dat daar ‘n verwantskap tussen die endoteel ATM proteïen kinase en die produksie van NO bestaan. Die seintransduksie paaie betrokke by NO produksie en glukose verbruik vorm ‘n interafhanklike netwerk. Die aktiwiteit van twee proteïen kinases, PKB/Akt en AMPK, is sentrale rolspelers in beide paaie. Albei hierdie kinases is daarvoor bekend dat hulle die eNOS ensiem fosforileer om NO te produseer, maar terselfdertyd ook lei tot AS160 fosforilering, wat tot GLUT 4 translokering en glukose opname lei. Dis is voorgestel dat aktivering van die ATM proteïen ‘n voorvereiste vir PKB/Akt aktivering mag wees en verder kan dit ook tot aktivering van AMPK lei. Ons kon nie aantoon dat inhibisie van ATM in endoteelselle die uitdrukking of insulien-geïnduseerde aktivering van PKB/Akt onderdruk nie, terwyl die PI3-K inhibitor, wortmannin, wel laasgenoemde geïnhibeer het. Verder het die inhibisie van ATM die fosfo/totale AMPK verhouding negatief gereguleer. Ons postuleer dus dat die NO produksie waargeneem tydens ATM inhibisie, moontlik nie die gevolg van eNOS aktiwiteit was nie. ‘n Tweede belangrike waarneming was dat die inhibisie van ATM die fosforilering van die p85 regulatoriese subeenheid van PI3-K beduidend laat toeneem het. Dit impliseer dat ATM normaalweg ‘n inhibitoriese effek op p85 fosforilering, en dus PI3-K aktivering, het. Hierdie aanname word gemaak n.a.v. vorige publikasies wat getoon het dat Ku-60019 nie PI3-K inhibeer nie. Dit dui weer eens daarop dat ATM ‘n tot nog toe onbekende regulatoriese rol in endoteelfunksie het.
85

Vascular endothelial growth factor (VEGF), BCL-2, and BAX expression in fibropapilloma tumor tissue and skin tissue of sea turtles

Unknown Date (has links)
In sea turtles, the study of the etiology and development of fibropapillomatosis is not fully understood. Sea turtle fibropapillomatosis is a disease characterized by the proliferation of skin fibropapillomas and occasional internal fibromas. In this study, sea turtle fibropapilloma tumor and healthy tissue samples were used to look at VEGF, BCL-2 and Bax expression. Cancer tumors have a well established pattern of protein expression that involves overexpression of vascular endothelial growth factor (VEGF), responsible for the growth of new blood vessels, and a high BCL-2 to Bax ratio that leads to uncontrolled cell proliferation. Real time PCR was used to analyze VEGF expression, and Western blot techniques were used to measure BCL-2 and Bax expression. The results indicated that expression of VEGF was not significantly higher in tumor vs. skin tissue. For the differential expression of BCL-2 and Bax, the results were not in agreement with the established levels found in cancer studies, showing no significant change in BCL-2 expression and significantly higher levels of Bax in tumor vs. healthy tissue. / by Angela Bancalari-Schmidlapp. / Thesis (M.S.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.
86

Middle cerebral artery (MCA) stenosis: genetic, pathological and imaging characterization. / CUHK electronic theses & dissertations collection

January 2006 (has links)
According to the literature, MRI has been applied to characterize the atherosclerosis in coronary and extracranial internal carotid artery. The cross-sections of MCA were scanned by Magnetic Resonance Imaging (MRI) to assess the accuracy of MRI in identifying MCA stenosis with histopathology as a golden standard, which was performed in the same post-mortem brains as in the second part. The sensitivity and specificity of MRI in detecting more than 30% MCA stenosis were 38.6% and 92.2%, with a positive predictive value of 87.2% and negative predictive value of 52.2%, and the corresponding values of MRI in identifying more than 50% MCA stenosis were 57.1%, 90.8%, 50% and 83.0%, respectively. Stenotic lesions >30% and >50% identified by MRI were found to be associated with infarctions in corresponding MCA territory. / After verification of potential relationship between ischemic stroke and intracranial artery calcification, the incidence of intracranial artery calcification was assessed in the ischemic stroke. One hundred and seventy-five ischemic stroke patients and 182 controls were enrolled. There was a higher prevalence of intracranial artery calcification in ischemic stroke patients than in controls. Hypertension, diabetes, smoking, intracranial artery calcification, hyperlipidemia, and atrial fibrillation were found to be independently associated with ischemic stroke. / Atherosclerotic stenosis is a heterogeneous disorder. The studies performed in extracranial carotid artery and coronary artery showed that the genes associated with lipoprotein metabolism may be associated with atherosclerosis. Thus, we speculated that the genes concerned with lipid metabolism may also be risk factors for MCA atherosclerotic stenosis. In the part of genetic analysis, clinical parameters and the genotypes of polymorphisms in the apolipoprotein E (ApoE), lipoprotein lipase (LPL), and paraoxonase (PON1) genes were compared in patients with and without MCA stenosis. Two hundred and ninety-four ischemic stroke patients were recruited, 136 cases with and 158 without MCA stenosis. Systolic blood pressure (SBP), rather than ApoE, LPL, and PON1 polymorphism was found to be a risk factor of MCA stenosis. / Calcification of intracranial artery, as a common complication of atherosclerosis, was investigated by multi-detector-row computed tomography (MDCT). By this advanced technique, the prevalence and location of calcification in intracranial arteries were determined, and its potential risk factors were also investigated. Four hundred and ninety patients were recruited. The incidence of intracranial artery calcification was 69.4%. The highest prevalence of intracranial artery calcification was seen in internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Age, a history of ischemic stroke, and white blood cell count were shown to be independently associated with intracranial artery calcification. / In the present study, genetic, pathological, imaging characterizations and prognosis of MCA stenosis were investigated. The effect of candidate genes has not been confirmed in the present study, but SBP and hypertension appears to contribute a lot to the occurrence of MCA stenosis among Chinese populations. As for the pathology of MCA atherosclerotic plaques, luminal stenosis and also the morphology of atherosclerotic plaque seem to play a cooperative role in leading to ischemic stroke. Imaging studies demonstrated the agreement between ex vivo MRI and histopathology in identifying MCA stenosis, and the correlation between the MCA stenosis identified by MRI and ischemic events. Calcification of intracranial artery, as a common complication of atherosclerosis, may be associated with age, history of ischemic stroke. High incidence of ischemic stroke has been demonstrated in Chinese type 2 diabetes patients. The presence of asymptomatic MCA stenosis plays an important role in the occurrence of ischemic stroke. / Lastly, using a cohort-study, we aimed to investigate stroke incidence of asymptomatic MCA stenosis and its risk factors in Chinese type II diabetic population. Transcranial Doppler was performed to define MCA stenosis. Incident strokes between 1996 and 2006 were ascertained by the database of Clinical Management System of the Hong Kong Hospital Authority. Anthropometric parameters (waist circumference and body mass index), blood pressure, and baseline plasma biochemical profile (lipid and glucose) were recorded to find the risk factors of ischemic stroke in asymptomatic MCA stenosis patients. Totally, 2,197 type II diabetic patients without symptoms of cerebrovascular disease were recruited. The evidence of MCA stenosis was identified in 272 subjects (12.4%), including 146 (53.7%) subjects with single-vessel involvement. Ischemic stroke occurred in one hundred and eighty-four (8.4%, 184/2197) patients. History of ischemic heart disease, MCA stenosis, the presence of retinopathy, lipid total cholesterol and age were independently associated with ischemic stroke. / Secondly, the pathological features of MCA stenosis and their relationship with cerebral infarcts were investigated in a series of post-mortem adults aged 45 years or above. The morphological features of the MCA atherosclerotic plaques were described in detail. The results demonstrated that the degree of luminal stenosis, the percentage of the plaques containing more than 40% lipid area, the values of cap-lipid, cap-lipid-stenosis, and the prevalence of intraplaque hemorrhage, neovasculature and thrombus were higher in the group of plaques associated with infarction. And the mean index of both CD45RO and CD68 were higher in the group of plaques associated with infarction. Binary logistic regression showed that stenosis, lipid area and presence of neovasculature were independent risk factors of MCA infarcts. / Stroke is one of the leading causes of death, disability, and dementia throughout the world. The stenosis of the intracranial large artery, especially the middle cerebral artery (MCA), is common in Chinese, Hispanic, and African populations. But MCA stenosis has been understudied due to its infrequency in the white population and its relative inaccessibility and invasiveness involved in its investigations. The purpose of the study was to investigate the genetic, pathological, imaging characteristics and prognosis of MCA atherosclerotic stenosis in Chinese population. / Chen Xiang-yan. / "September 2006." / Adviser: MH Ng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1460. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 193-212). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
87

Brainstem functional changes in response to alteration of bladder function. / CUHK electronic theses & dissertations collection

January 2006 (has links)
Background and purpose. Recent studies have shown that the children with severe nocturnal enuresis, or bedwetting, often have underlying bladder dysfunction as well as various types of brainstem disorders, including arousal inability, a deficient response to startle sounds, or prepulse inhibition. Since the pontine micturition centre is anatomically very close, even overlapping with the nuclei responsible for sleep arousal, one may speculate that there may be close inter-relationships between abnormal bladder function, brainstem dysfunction and sleep-arousal disturbance. We hypothesize that the brainstem function would be changed in response to alteration of bladder function. Using conventional-fill cystometric study, functional magnetic resonance imaging (fMRI) scanning and immunohistochemistry approaches, we propose to characterize the functional changes in the brainstem in response to altered bladder function (i.e. surgically reduced bladder capacity). / Conclusions. Our results showed that bladder dysfunction elicited by surgical reduction in bladder capacity can induce functional changes in the central nervous system. In response to surgical reduction in bladder capacity, deactivation in the vlPAG was detected suggesting that the vlPAG plays a role in the biofeedback of bladder dysfunction. / Data are expressed as the mean +/-1SD unless otherwise specified. Appropriate statistical tests were used for parametric and non-parametric testing between the groups by using the SPSS computer program. In all comparisons a statistical significance level of 95% (p&lt;0.05) was chosen. / Immunohistochemistry study showed a significant decrease in the reaction of dopaminergic neuron in the correspondent regions, suggesting a dopaminergic dependent change in the vlPAG in response to the bladder dysfunction. / In addition, we will explore the use of electroacupuncture (EA), a traditional Chinese therapy that has been broadly used for treatment of bladder functional disorders, to modulate functional changes in the central nervous system. We hypothesize that functional change in various nuclei in the central nervous system that are responsible for micturition control can also be affected by acupuncture treatment. A further aim of this study was to identify brain areas involved in EA to acupoint Chiliao (BL 32), a special acupoint broadly used for the treatment of bladder disorders. / Materials and methods. The study was divided into four parts. Seventy-five male New Zealand white rabbits (14-16 weeks, mean body weight: 3.0-3.5 kg) were used. / Moreover, in this study, we also found a notable activation in the vlPAG and dlPONS in response to the acupuncture stimulations to acupoint Chiliao (BL 32). The changes were identical to that induced by the bladder distension, suggesting a neuromodulation in central nervous system in response to acupuncture therapy. / Results. Study I: Bladder dysfunction elicited by surgical reduction in bladder capacity. Compared to sham animals, the maximum cystometric capacity in animals with RBC operation was markedly decreased at week 4 (35.3+/-8.2 ml vs. 71.6+/-12.9 ml, p&lt;0.05), and week 8 (46.2+/-12.1ml vs. 82.7+/-20.1 ml, p&lt;0.05) groups respectively; however, the maximum voiding detrusor pressure was significantly increased at week 4 (24.4+/-7.0 vs.16.5+/-7.2 cm water, p&lt;0.05) and week 8 (27.7+/-8.p vs. 16.8+/-7.5 cm water, p&lt;0.05) groups respectively, and their corresponding vesical pressure was also enhanced. Other parameters including maximum flow rate, and bladder emptying efficiency did not change significantly in between the sham and RBC subgroups. / Study I: Establishment of the dysfunctional bladder animal model with small bladder capacity. Forty rabbits underwent either sham operation (n=20) or operation for reduced bladder capacity (RBC) (n=20). The sham-operated and the RBC animals were further divided into two groups, i.e. four, and eight weeks after operation (n=10 in each sham and RBC subgroup). A conventional-fill cystometric study was performed on these animals whilst awake in order to evaluate the functional changes (if any) in response to surgical bladder capacity reduction, compared to sham subgroup. / Study II: Detection of functional changes in the brainstem in response to bladder dysfunction. FMRI scanning was performed at the brainstem region in sham-operated and RBC rabbits (12 in each group) at four weeks postoperatively. Bladder stimulation was provided by warm saline (37&deg;C) infusion through a urethral catheter until bladder distended to 70% of the maximum capacity. Area(s) of brainstem activation were assessed by comparing the fMRI scans performed before and after warm saline infusion. / Study II: Functional changes in brainstem in response to bladder dysfunction. FMRI scanning results demonstrated that for the sham animals, there were two activated regions in the brainstem in response to bladder distention, one in the ventrolateral region of periaqueductal gray (vlPAG, 83.3%, 10/12), and the other in the dorsolateral region of pons (dlPONS, 91.7%, 11/12). In animals with RBC operation, only 25% (3/12) showed vlPAG activation compared to 83.3% (10/12) in sham group (p&lt;0.05); however, 83.3% (10/12) of animals showed similar dlPONS activation compared to 91.7% in sham group (p>0.05). / Study III: Catecholaminergic neurotransmitters changes in the brainstem affected areas in response to bladder dysfunction. Brainstem immunohistochemistry results showed that a large number of dopaminergic neuron scattered throughout the whole vlPAG, rarely appeared in dlPAG (dorsolateral region of periaqueductal gray) (lambda +6.0 to +3.0 mm); and an abundant noradrenergic neurons were also accumulated in a restricted region of dlPONS (lambda +3.0 to 0 mm). Compared with the sham group, the density of TH-positive neurons in the vlPAG was significantly decreased in RBC group (38.38+/-4.71 vs.51.57+/-8.38/field, p&lt;0.05); for the another region of dlPONS, although the density of TH-positive neurons decreased slightly in RBC group compared to sham group, the results showed no statistical difference between groups (106.89 +/- 21.61 vs.120.61 +/- 17.03/field, p>0.05). / Study III: Investigation of the catecholaminergic neurotransmitters changes in brainstem affected areas in response to bladder dysfunction. After fMRI examination, all animals were euthanized, and their brainstems were collected for immunohistochemistry study with tyrosine hydroxylase, dopamine-beta-hydroxylase assays to investigate the changes of catecholaminergic neurotransmitters including dopaminergic, noradrenergic and adrenergic in response to bladder dysfunction elicited by surgical reduction in bladder capacity. / Study IV: Electroacupuncture modulation via acupoint Chiliao (BL 32) on bladder and the brainstem activated sites. FMRI study showed that the two brainstem micturition centers of the vlPAG (72.7%, 8/11) and dlPONS (82.8%, 9/11) can be activated by EA on BL 32, and there were no significant difference compared with stimulation of bladder distention (72.7% vs. 83.3% in vlPAG and 82.8% vs. 91.7% in dlPONS respectively, p>0.05). Urodynamic results showed that, bladder contraction obviously evoked in response to EA on BL 32 (ON-EA state) compared to before EA state (OFF-EA state), displaying a significantly increased detrusor pressure (14.04+/-3.17 vs. 8.19+/-0.69 cm water, p&lt;0.05) and vesical pressure (13.48+/-1.61vs. 7.90+/-0.81 cm water, p&lt;0.05). In addition, dissection of BL 32 showed that the stem of S1 and S2 pass through the region 0.5 cm around the acupuncuture needle. / Study IV: Investigation of electroacupuncture modulation via acupoint Chiliao (BL 32) on bladder and the brainstem activated sites. FMRI scanning and urodynamic evaluation were performed respectively during ON/OFF EA on acupoint Chiliao (BL 32) on sham-operated animals (n=12) at four weeks post-operation. At last, dissection of acupoint BL 32 was performed on seven sham animals. / We also found that surgically induced bladder dysfunction, mainly displaying as reduced bladder capacity and maximum voiding detrusor pressure enhanced, was elicited at four to eight weeks after the surgical reduction in bladder capacity in rabbit. / Xiang Bo. / "August 2006." / Adviser: Chung Kwong Yeung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1551. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 161-196). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.
88

The regulation of vitamin D metabolism in the kidney and bone

Anderson, Paul Hamill. January 2002 (has links) (PDF)
Includes bibliographical references (leaves 226-273.) Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone.
89

The regulation of vitamin D metabolism in the kidney and bone

Anderson, Paul Hamill. January 2002 (has links)
Includes bibliographical references. Electronic publication; Full text available in PDF format; abstract in HTML format. Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone. Electronic reproduction.[Australia] :Australian Digital Theses Program,2001.
90

Developing a ‘ubiquitous’ toolkit for modulating ion channel expression in health & disease

Kanner, Scott Arthur January 2021 (has links)
Protein stability is critical for the proper function of all proteins in the cell. Ubiquitin is a key post-translational modification that serves as a universal regulator of protein turnover and has emerged as a highly sought-after signal for biological inquiry and drug development. Yet the pervasive role of ubiquitin signaling has given rise to the fundamental challenge of selectively manipulating a widespread signal: current pharmacological and genetic tools that target the ubiquitin-proteasome system (UPS) broadly alter cellular proteostasis with confounding side effects. Ion channels are essential proteins that regulate fundamental cellular properties including; electrical activity, fluid homeostasis, muscle contraction, neuronal firing, gastric acidification, and gene expression. Enhanced or reduced ion channel expression represents a pathological signature for a myriad of disease states, from chronic pain to cardiac arrhythmias, epilepsy, and cystic fibrosis. Although ubiquitin represents a critical mediator of ion channel expression, the inability to precisely manipulate ubiquitin modifications in situ has limited mechanistic insight and opportunities for therapeutic intervention. To address this barrier, I developed a novel nanobody-based toolset to selectively – and bidirectionally – manipulate the ubiquitin status and functional expression of target ion channels for basic study and therapeutic rescue.

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