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Background: Hepatocellular carcinoma (HCC) is one of the most common primary liver tumors in humans and dogs. Excessive adrenocortical hormone exposure may cause steroid hepatopathy, which may develop into HCC. In our previous study, hyperadrenocorticism (HAC) was a highly concurrent disease in dogs with HCC. Therefore, this study hypothesized that adrenal steroid alterations might be involved in hepatocarcinogenesis and aimed to specify the relationship between HAC and HCC in dogs. Materials and methods: This study included 46 dogs brought to the Hokkaido University Veterinary Teaching Hospital between March 2019 and December 2020. Owners gave their signed consent for blood collection on their first visit. A total of 19 steroids (14 steroids and 5 metabolites) in the baseline serum of 15 dogs with HCC, 15 dogs with HAC, and 10 dogs with both diseases were quantitatively measured using the developed liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) method. Results: In each group, 11 steroids were detected higher than 50%. The detection rate of steroid hormones did not significantly differ between the groups (p > 0.05). Principle component analysis (PCA) showed that the steroid profiles of the three groups were comparable. Median steroid hormone concentrations were not significantly different between the study diseases (p > 0.05). Conclusion: The developed LC/MS/MS was useful for measuring steroid hormones. Although it was clear that HAC was concurrent in dogs with HCC, none of the serum steroids was suggested to be involved in HCC.

Background: Hepatocellular carcinoma (HCC) is one of the most common primary liver tumors in humans and dogs. Excessive adrenocortical hormone exposure may cause steroid hepatopathy, which may develop into HCC. In our previous study, hyperadrenocorticism (HAC) was a highly concurrent disease in dogs with HCC. Therefore, this study hypothesized that adrenal steroid alterations might be involved in hepatocarcinogenesis and aimed to specify the relationship between HAC and HCC in dogs. Materials and methods: This study included 46 dogs brought to the Hokkaido University Veterinary Teaching Hospital between March 2019 and December 2020. Owners gave their signed consent for blood collection on their first visit. A total of 19 steroids (14 steroids and 5 metabolites) in the baseline serum of 15 dogs with HCC, 15 dogs with HAC, and 10 dogs with both diseases were quantitatively measured using the developed liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) method. Results: In each group, 11 steroids were detected higher than 50%. The detection rate of steroid hormones did not significantly differ between the groups (p > 0.05). Principle component analysis (PCA) showed that the steroid profiles of the three groups were comparable. Median steroid hormone concentrations were not significantly different between the study diseases (p > 0.05). Conclusion: The developed LC/MS/MS was useful for measuring steroid hormones. Although it was clear that HAC was concurrent in dogs with HCC, none of the serum steroids was suggested to be involved in HCC.

Xu Li., Thesis (Ph.D.)--Chinese University of Hong Kong, 2011., Includes bibliographical references (leaves 204-242)., Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web., also in Chinese., http://library.cuhk.edu.hk/record=b6075405, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Xu Li., Thesis (Ph.D.)--Chinese University of Hong Kong, 2011., Includes bibliographical references (leaves 204-242)., Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web., also in Chinese., http://library.cuhk.edu.hk/record=b6075405, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Chiu, Wang Kei., Thesis (M.Phil.)--Chinese University of Hong Kong, 2007., Includes bibliographical references (leaves 95-110)., s in English and Chinese., p.i, 摘要 --- p.iii, Contents --- p.v, Acknowledgements --- p.viii, Abbreviations --- p.ix, List of tables --- p.xii, List of figures --- p.xii, Chapter 1. --- Literature Review --- p.1, Chapter 1.1 --- Cell cycle and chromosome replication --- p.1, Chapter 1.2 --- Telomere-associated proteins --- p.4, Chapter 1.3 --- Telomere repair protein --- p.6, Chapter 1.4 --- Function of telomere --- p.9, Chapter 1.5 --- Telomerase --- p.10, Chapter 1.6 --- Factors affecting telomere length --- p.14, Chapter 1.7 --- Stress and telomere length --- p.14, Chapter 1.8 --- Definition of Stress --- p.16, Chapter 1.9 --- Central nervous system components involved in stress response --- p.17, Chapter 1.10 --- Glucocorticoid --- p.17, Chapter 1.11 --- Physiological effects under the activation of stress system --- p.19, Chapter 1.12 --- Effects of chronic hyperactivation of the stress system --- p.20, Chapter 1.13 --- Hypothesis --- p.23, Chapter 2. --- Materials and Methods --- p.24, Chapter 2.1 --- Materials --- p.24, Chapter 2.2 --- Experiment animals --- p.25, Chapter 2.3 --- Methods --- p.26, Chapter 2.3.1 --- Treatment schedule --- p.26, Chapter 2.3.2 --- Organ extraction and serum preparation --- p.27, Chapter 2.4 --- Serum corticosteroid assay --- p.27, Chapter 2.5 --- Telomere length assay --- p.30, Chapter 2.5.1 --- Genomic DNA extraction --- p.30, Chapter 2.5.2 --- Genomic DNA digestion --- p.31, Chapter 2.5.3 --- Southern blotting procedure --- p.32, Chapter 2.6 --- Telomeric Repeat Amplification Protocol (TRAP) assay --- p.37, Chapter 2.6.1 --- Extract preparation and protein concentration quanititation --- p.38, Chapter 2.6.2 --- Real-time PCR reaction --- p.39, Chapter 2.6.3 --- Melt Curve --- p.41, Chapter 2.7 --- Detection of mouse telomerase reverse transcriptase component (mTERT) mRNA expression by reverse transcriptase- polymerase chain reaction (RT-PCR) --- p.42, Chapter 2.7.1 --- Total RNA extraction --- p.42, Chapter 2.7.2 --- RT-PCR --- p.44, Chapter 2.7.3 --- Agarose gel electrophoresis of RT-PCR products --- p.45, Chapter 2.8 --- Detection of mouse TERT (mTERT) by Western blotting --- p.46, Chapter 2.8.1 --- Nuclear protein extraction --- p.46, Chapter 2.8.2 --- Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) --- p.47, Chapter 2.9 --- Statistics --- p.49, Chapter 3. --- Results --- p.51, Chapter 3.1 --- Body and spleen weights of study animals --- p.51, Chapter 3.2 --- Serum corticosterone level --- p.54, Chapter 3.3 --- Telomere lengths of spleen --- p.54, Chapter 3.4 --- Telomerase activity of spleen tissue --- p.58, Chapter 3.5 --- Correlation between serum corticosterone level and telomere length --- p.65, Chapter 3.6 --- Correlation between serum corticosterone level and telomerase activity --- p.66, Chapter 3.7 --- Correlation between telomere length and telomerase activity --- p.67, Chapter 3.8 --- Detection of telomerase reverse transcriptase component (mTERT) mRNA expression by RT-PCR --- p.69, Chapter 3.9 --- Detection of mTERT by Western blotting --- p.72, Chapter 3.10 --- Correlation between serum corticosterone level and mTERT mRNA /protein expression --- p.75, Chapter 4. --- Discussion --- p.77, Chapter 4.1 --- Serum corticosterone level in mice --- p.78, Chapter 4.2 --- Mice body weight and spleen weight --- p.80, Chapter 4.3 --- Telomere lengths in the spleen tissue --- p.83, Chapter 4.4 --- Telomerase activity in spleens --- p.84, Chapter 4.5 --- Correlation between serum corticosterone level and telomere length --- p.87, Chapter 4.6 --- Correlation between serum corticosterone level and telomerase activity --- p.89, Chapter 4.7 --- Mouse telomerase reverse transcriptase component (mTERT) mRNA expression --- p.89, Chapter 4.8 --- Expression of mTERT protein --- p.90, Chapter 4.9 --- Conclusion --- p.92, Chapter 5. --- References --- p.95, Chapter 6. --- Appendix --- p.111, http://library.cuhk.edu.hk/record=b5893247, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

English: The etiology of aggression and self-injuring behaviour in low functioning mentally retarded patients is multi-factorial and may reflect the presence of undiagnosed psychiatric conditions, unapparent due to the degree of the patient's impairment. It may also reflect hyperactivity of the stress response. The intricacies of diagnosis in this group of patients call for the development of biological markers to aid in diagnosis, therapy selection and drug response monitoring. Measuring and determining the relative contribution of individual neurotransmitters in the problem behaviour is complex and impractical. An alternative route may be to evaluate the functions of the hypothalamic-pituitary axis, which has extensive connections with the limbic area and is relatively easy to assess. The hypothalamic-pituitary system controls the behavioural, endocrine, autonomic and immunological responses to stress. The dexamethasone suppression test (OST) as adapted by Carroll and the thyroid-releasing hormone stimulation test (TRHST) has been extensively used in research on biological markers in major depression. Stress is known to activate the hypothalamic-pituitary-adrenal (HPA) axis, reflected by elevated cortisol levels. The study is a matched control study comparing hypothalamic-pituitary-adrenal axis function and hypothalamic-pituitary-thyroid axis function in 44 institutionalised mentally retarded patients with and without self-injuring and aggressive behaviour through the measurement of baseline cortisol levels and the application of the dexamethasone suppression test and the thyroid-releasing hormone stimulation test. The groups were matched according to gender, age and level of functioning. The mean age of the aggressive group 106 was 44,1 years (±SO 9,8) and the mean age of the non-aggressive group was 44,2 years (±SO 10,5). Baseline hypercortisolaemia occurred in five of the 22 aggressive subjects (22,7 %) and in two of the 22 non-aggressive subjects (9,1 %). Cort, Afrikaans: Die etiologie van aggressiewe en selfbeserende gedrag in laag funksionerende verstandelik vertraagde pasiënte is multi-faktoriaal en mag moontlik die teenwoordigheid van ongediagnoseerde psigiatriese toestande insluit wat nie herken word nie weens die graad van die pasiënt se gestremdheid. Dit mag ook hiperreaktiwiteit van die stresrespons insluit. Biologiese merkers mag van groot waarde wees om te help met diagnose, seleksie van terapie en middelmonitering in hierdie pasiënte. Die meting van en bepaling van die relatiewe bydrae van individuele neurotransmittors tot die probleemgedrag is egter kompleks en onprakties. As' n alternatief mag dit van waarde wees om die funksies van die hipotalamus-hipofise-as te evalueer, aangesien die as uitgebreide verbindings met die limbiese area het en relatief maklik geëvalueer kan word. Die hipotalamus-hipofisesisteem beheer die gedrags-, endokriene, outonome en immunologiese response tot stres. Die deksametasoononderdrukkingstoets (DST) soos aangepas deur Carroll en die tiroïedvrystellingshormoonstimulasietoets (TRHST) word lank reeds gebruik in navorsing oor biologiese merkers in major depressie. Dit is bekend dat stres die hipotalamus-hipofise-bynieras aktiveer, soos gereflekteer deur verhoogde kortisolvlakke . Die studie is 'n gepaarde kontrolestudie waarin die hipotalamus-hipofisebynierasfunksie en die hipotalamus-hipofise-tiroïedasfunksie in 44 geïnstitusionaliseerde verstandelik vertraagde pasiënte met en sonder selfbeserende en/of aggressiewe gedrag met mekaar vergelyk word. Daar word gebruik gemaak van die meting van basislynkortisolvlakke, die deksametasoononderdrukkingstoets soos aangepas deur Carroll en die tiroïedvrystellingshormoonstimulasietoets. Die groepe is gepaar met betrekking tot geslag, ouderdom en vlak van funksionering. Die gemiddelde ouderdom van die aggressiewe groep was 44,1 jaar (±SD 9,8) en die gemiddelde ouderdom van die nie-aggressiewe groep was 44,2 jaar (±SD 10,5). Basislynhiperkortisol, Faculty of Health Sciences, Department of Pharmacology

by Martin Li., Year shown on spine: 1997., Thesis (M.Phil.)--Chinese University of Hong Kong, 1996., Includes bibliographical references (leaves 150-157)., DECLARATION --- p.II, p.III, ACKNOWLEDGEMENTS --- p.VII, CONTENTS --- p.VIII, LIST OF ABBREVIATIONS --- p.XIV, LIST OF TABLES --- p.XVI, LIST OF CHART --- p.XXIII, LIST OF FIGURES --- p.XXIV, Chapter CHAPTER 1 --- OBSTRUCTIVE AIRWAY DISEASE: PUBLIC HEALTH AND CLINICAL ASPECTS --- p.1, Chapter 1.1. --- Background --- p.1, Chapter 1.2. --- Magnitude of the problem --- p.2, Chapter 1.2.1. --- Asthma --- p.2, Chapter 1.2.2. --- Chronic obstructive pulmonary disease --- p.3, Chapter 1.2.3. --- Prevalence of osteoporosis in Hong Kong --- p.4, Chapter 1.2.4. --- History of asthma care --- p.5, Chapter 1.2.5. --- Treatment of OAD --- p.5, Chapter 1.3. --- Side effects of Glucocorticoid in OAD patients --- p.6, Chapter 1.4. --- Side effccts of inhaled corticosteroids in OAD patients --- p.7, Chapter 1.5. --- Trend of asthma therapy in Hong Kong --- p.8, Chapter CHAPTER 2: --- OSTEOPOROSIS: PUBLIC HEALTH AND CLINICAL ASPECTS --- p.11, Chapter 2.1. --- Bone Biology --- p.11, Chapter 2.2. --- Skeletal Organisation --- p.11, Chapter 2.3. --- Bone remodelling --- p.12, Chapter 2.4. --- Effect of corticosteroids on bone remodelling --- p.13, Chapter 2.5. --- Corticosteroids induccs osteoporosis --- p.13, Chapter 2.6. --- Factors affecting BMD --- p.14, Chapter 2.6.1. --- Peak bone mass --- p.14, Chapter 2.6.2. --- Ethnic factors --- p.14, Chapter 2.6.3. --- Aging --- p.15, Chapter 2.6.4. --- Calcium intake --- p.15, Chapter 2.6.5. --- Oestrogen --- p.16, Chapter 2.6.6. --- Alcohol consumption --- p.17, Chapter 2.6.7. --- Cigarette smoking --- p.17, Chapter 2.7. --- Physical activity and BMD --- p.17, Chapter 2.8. --- Body composition in Chinese subjects --- p.18, Chapter CHAPTER 3 --- "PHASE I: BODY COMPOSITION AND BONE MINERAL DENSITY IN OBSTRUCTIVE AIRWAY DISEASE PATIENT AND NORMAL CONTROL SUBJECTS: OBJECTIVES, SUBJECTS AND METHODS" --- p.20, Chapter 3.1. --- Objectives --- p.20, Chapter 3.2. --- Subjects and methods --- p.21, Chapter 3.2.1 --- OAD patients --- p.21, Chapter 3.2.1.1 --- Disease definition and selection criteria --- p.21, Chapter 3.2.1.2. --- Normal Control subjects --- p.21, Chapter 3.3. --- Power of estimation --- p.22, Chapter 3.4. --- Survey methods --- p.22, Chapter 3.5. --- Questionnaire --- p.23, Chapter 3.6. --- Body composition and bone mineral density measurement --- p.23, Chapter 3.6.1. --- Body composition analysis --- p.24, Chapter 3.6.2. --- Lumbar spine and proximal hip bone mineral density analysis --- p.24, Chapter 3.6.3. --- Routine quality control of measurements --- p.24, Chapter 3.6.4. --- Precision on patient repositioning --- p.25, Chapter 3.7. --- Statistical methods --- p.25, Chapter 3.8. --- Bone mineral density of normal control subjects --- p.25, Chapter CHAPTER 4 --- PHASE II: FLUORIDE IN THE TREATMENT OF OSTEOPOROSIS --- p.27, Chapter 4.1. --- Introduction --- p.27, Chapter 4.2. --- Mechanisms of action --- p.28, Chapter 4.2.1. --- Antiresorptive effect of fluoride --- p.28, Chapter 4.2.2. --- Force-oriented osteogenic effect of fluoride --- p.28, Chapter 4.2.3. --- Biochemical osteogenic effect --- p.29, Chapter 4.3. --- Effect of fluoride salts on BMD: results of clinical trials --- p.29, Chapter 4.4. --- Effcct of fluoride on bone histomorphology --- p.30, Chapter 4.5. --- Compliance with sodium fluoride therapy --- p.31, Chapter 4.6. --- Contradiction of fluoride treatment --- p.31, Chapter 4.7. --- Sodium monofluorophosphate preparation --- p.32, Chapter CHAPTER 5 --- PHASE II: THE EFFECTS OF FLUORIDE ON BONE MINERAL DENSITY OF OAD PATIENTS ON STEROID TREATMENT --- p.37, Chapter 5.1. --- Objectives --- p.37, Chapter 5.2. --- Subjects and methods --- p.37, Chapter 5.2.1. --- Power of the study --- p.37, Chapter 5.2.2. --- Subjects --- p.37, Chapter 5.2.3. --- Method of randomisation --- p.38, Chapter 5.2.4. --- Treatment modalities --- p.39, Chapter 5.2.4.1. --- Treatment group --- p.39, Chapter 5.2.4.2. --- Control group --- p.39, Chapter 5.2.5. --- Bone mineral density measurements --- p.39, Chapter 5.2.6. --- Routine quality control of measurement and precision on patient repositioning --- p.40, Chapter 5.2.7. --- Methods of monitoring drug compliance --- p.40, Chapter 5.2.8 --- Statistical methods --- p.40, Chapter CHAPTER 6 --- RESULTS FOR PHASE I --- p.42, Chapter 6.1. --- Statistical power of this phase of the study --- p.42, Chapter 6.2. --- Clinical features of OAD subjects on inhaled steroid --- p.42, Chapter 6.3. --- Anthropometric measurements and bone mineral density --- p.45, Chapter 6.4. --- Analysis of covariance for BMDs differences --- p.48, Chapter 6.5. --- Multiple regression --- p.50, Chapter 6.6 --- Correlation --- p.51, Chapter CHAPTER 7 --- RESULTS FOR PHASE II: FLUORIDE AND CALCIUM TRIAL --- p.81, Chapter 7.1. --- Factors affects the power of studies --- p.81, Chapter 7.2. --- Clinical findings --- p.82, Chapter 7.3. --- Body measurements and bone mineral densitometry --- p.85, Chapter CHAPTER 8: --- DISCUSSION FOR PHASE I --- p.117, Chapter CHAPTER 9: --- DISCUSSION FOR PHASE II: TRIDIN AND CALCIUM TRIAL --- p.124, APPENDIX 1: QUESTIONNAIRE FOR OAD BONE MINERAL DENSITY STUDY --- p.132, APPENDIX 2: BONE SCANS FROM HOLOGIC QDR2000 --- p.137, APPENDIX 3. TABLES AND REFERENCE CURVES FOR NORMAL HONG KONG CHINESE FEMALE OR MALE BMD --- p.142, REFERENCE --- p.150, http://library.cuhk.edu.hk/record=b5889154, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

by Pik-ying Ng., Bibliography: leaves 106-117, Thesis (M.Phil.)--Chinese University of Hong Kong, 1983, http://library.cuhk.edu.hk/record=b5885377, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

by Pik-ying Ng., Bibliography: leaves 106-117, Thesis (M.Phil.)--Chinese University of Hong Kong, 1983, http://library.cuhk.edu.hk/record=b5885377, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Corticosteroid medicines have anti-inflammatory and immunosuppressant effects. Corticosteroids are prescribed for a wide range of conditions in children. The duration of treatment ranges from a few days (short course) to long term. They are usually given orally in the different dosage form of tablets, syrup or soluble tablets. There are a wide range of adverse drug reactions (ADRs) associated with corticosteroids. This thesis initially evaluates the incidence of each individual ADR in children using systematic reviews. Prospective studies of palatability and pharmacoepidemiology using different methods are also used to evaluate aspects of using corticosteroids in children in Saudi Arabia and the UK. A systematic review of the toxicity of short-course oral corticosteroids in children was conducted. Six electronic databases were searched for articles that evaluated the toxicity of oral corticosteroids in children for up to and including 14 days of treatment. Thirty eight articles including 22 randomised controlled trials (RCTs). The review found that the three most frequent ADRs were vomiting, behavioural changes and sleep disturbance, with incidence rates of 4.3 – 5.4% of patients. Infection was one of the most serious ADRs. A systematic review of the toxicity of long-course oral corticosteroids in children was conducted. One hundred studies including 33 prospective cohort studies and 21 RCTs met the inclusion criteria. The review found that the three most frequent ADRs were weight gain, growth retardation and Cushingoid features, with incidence rates of 18.1 – 21.1% of patients. Infection was one of the most serious ADRs, with twenty one deaths. Hypothalamic-pituitary-adrenal (HPA) axis suppression was detected in 249 of 429 patients in whom it was measured. Based on the findings that were highlighted from the systematic review, a prospective observational/interview study was performed. This study evaluated the tolerability and palatability of oral prednisolone and

Biochemical and physiological indices of stress showed that the level of stress of 16 air traffic controllers at the Houston Intercontinental Airport Tower was indistinguishable from that of control populations. While the level of stress was lower than that among O'Hare Tower controllers, both groups showed about the same degree of adaptation., Day work (heavy traffic load) at Houston was characterized by elevated levels of all stress indicators as compared with the mid-shift (light traffic); epinephrine excretion increased significantly during the last half of the mid-shift as compared with the first half. Urinary stress indicators (17-ketogenic steroids, epinephrine, norepinephrine) were all significantly elevated during day sleep as compared with night sleep, indicating less effective rest during day sleep.

Eleven male subjects were given flight training according to a conventional but rigidly standardized private pilot syllabus. On half of the dual flights chloridazepoxide was given; identical-appearing placebo capsules were given on the remaining dual flights. No treatment was given on solo flights. Differences could not be distinguished between tranquilizer and placebo with respect to the urinary excretion of catecholamines and 17-OH corticosteroids and heart rates recorded continuously in flight

Pre-flight and post-flight studies were carried out on five air tanker pilots; in-flight studies were carried out on four of these five pilots. Pre- and post-flight studies consisted of a questionnaire and determinations of blood pressure, psychomotor performance and urine chemistry for stress metabolites. In-flight studies consisted of ECG, rectal temperature, cockpit temperature and voice transmissions, all continuously recorded on magnetic tape.

Stress in controllers on the straight five-day shift was determined at Houston Intercontinental Tower in 1970. In 1971 controllers on the 2-2-1 rotation were studied at the same tower. Controllers generally prefer the 2-2-1 to the straight five-day schedule because of the long week end associated with the 2-2-1. Management is concerned that the 'quick turnaround' on the 2-2-1 is a stressor that could compromise job performance., Physiological and psychological assessments showed no significant stress differences on the two schedules. On neither of the schedules did the controllers' stress levels differ from the general polulation., It was concluded that the stress differences on the two rotation patterns were too slight to be of real significance and a choice between them would have to rest on managerial considerations rather than biomedical ones.

Findings are presented on the consequences of rapidly crossing numerous time zones, such as occurs in present-day jet aircraft travel. Conclusions reached by FAA researchers and scientists of other laboratories are included, together with recommendations for overcoming time-zone fatigue. These recommendations are for use by the individual long distance traveler. A practical formula is given which describes how one may compute the rest period following a long distance trip. This period is to enable the biological rhythms to rephase in order that the traveler will be in proper physical and mental condition to pursue his responsibilities.