Vascular access-related bloodstream infection (BSI) is frequent among patients undergoing hemodialysis increasing significantly their morbidity and mortality. Studies assessing centre- and patient-predictors of BSI have had inadequate sample size and follow-up time. The aims of this project are: to describe the incidence rates; and to determine patient- and centre-level predictors of BSI in a cohort of incident hemodialysis patients treated in teaching or community hospitals, and in First Nation dialysis units. The rates of BSI in our population were lower than those observed in other settings. Central venous catheters were the most important risk factor for BSI and their use in our study was much higher than recommended. Some variability in BSI rates was found among centres, but no centre-related variable was found to be associated with the risk of BSI. Effort to reduce catheter use in hemodialysis patients may significantly reduce the risk of BSI in this patient population.

Os efeitos tóxicos decorrentes da exposição ambiental e ocupacional ao benzeno são amplamente descritos na literatura. Seus produtos de biotransformação fenólicos, entre os quais os compostos hidroxilados como FE e hidroquinona HQ, são indutores importantes de efeitos citotóxicos e genotóxicos responsáveis pela toxicidade ao sistema imune. No entanto, a contribuição de cada metabólito e os mecanismos envolvidos não estão completamente esclarecidos. Desta forma, o presente trabalho teve por objetivo estudar a capacidade da resposta inflamatória em ratos expostos à HQ, ao FE, ou a ambos simultaneamente (HQ+FE). Para tanto, ratos Wistar machos foram expostos aos agentes químicos por período de tempo prolongado (doses diárias de 5 ou 10mg/kg; i.p.; com 5 doses/semana no período de 17 ou 23 dias). Animais controles receberam o veículo pela mesma via. As respostas inflamatórias foram induzidas 24 horas após a última dose administrada. Foram avaliadas a resposta inflamatória inespecífica, decorrente da instilação intranasal de LPS de Salmonella abortus e a resposta inflamatória específica em animais previamente sensibilizados e desafiados pela OVA. Na resposta inflamatória inespecífica, as exposições à HQ e à HQ+FE provocaram redução acentuada no influxo de leucócitos para o pulmão inflamado, pelo menor número de leucócitos no LBA e pela atividade enzimática da MPO reduzida no tecido pulmonar. O efeito não é dependente de modificações no número de leucócitos circulantes nem de alterações nas expressões de moléculas de adesão nos leucócitos circulantes (L-selectina e β2 integrina) e no endotélio pulmonar (ICAM-1 , VCAM-1 e PECAM-1) envolvidas na interação leucócito-endotélio. Na vigência de resposta inflamatória específica, as exposições à HQ, FE ou HQ+FE reduziram significativamente a migração de leucócitos para o LBA e para o tecido pulmonar. Da mesma forma que a RI induzida pelo LPS, não foram detectados alterações nos número de leucócitos circulantes e na expressão de moléculas de adesão. No entanto, os resultados obtidos em ensaios de anafilaxia passiva cutânea e reação anafilática in vitro mostraram que o efeito é dependente, pelo menos em parte, da menor concentração de imunoglobulinas anafiláticas circulantes e, consequentemente, da menor habilidade de desgranulação mastocitária. Em conjunto, os dados obtidos demonstram que as exposições à HQ, ao FE ou à HQ+FE prejudicam a migração de leucócitos para o foco de lesão na vigência de respostas inflamatórias de origem inata ou adquirida. / The toxic effects of the ambiental and occupational exposures to benzene is widely described in the literature. Phenolic hydroxylated compounds obtainded from its biotransformation, such as phenol (PHE) and hydroquinone (HQ), induce important of cytotoxic and genotoxic effects responsible for the immunotoxicity. However, the role of each metabolite and mechanisms of toxicity are unknown. Then, the present work aimed to study the inflammatory response in rats exposed to HQ, PHE, ar both simultaneously (HQ+PHE). Male Wistar rats were exposed to they chemical agents for extended period of time (5 or 10mg/kg/day; ip.; during 17 or 23 days; 2 days intervals each 5 doses). Control animais received the vehicle. Inflammatory reactions were induced 24 hours after the last dose by they intranasal instillation of lipopolysaccharide of Salmonella aborlus (non-specific response) or by inhalation of ovalbumin in animals previously sensitized to the same antigen (specific response, produced by anaphylactic immunoglobulins). Animais exposed to HQ or HQ/PHE presented reduced n,3umbers of PMN and MN cells in the bronchoalveolar lavage fluid (BALF) and lesser myeloperoxidase (MPO) activity in the pulmonary tissue. The reduced influx of leukocytes is not dependent oh alterations on the numbers of circulating leukocytes either adhesion molecules expressions on leukocytes (L-selectin or β2 integrin) and on lung microvascular endothelium (ICAM-1, V CAM-1 or PECAM-1) responsible for leukocyte-endothelial interactions. On the other hand, rats exposed to ali schedules of exposures presented reduced numbers of leukocytes in the BALF and lesser MPO activity in the pulmonary tissue after an antigenic stimulus. As shown to inflammation induced by LPS, no alterations on circulating leukocyte numbers and adhesion molecules expressions were detected. However, the impaired leukocyte migration to the inflamed lung may be dependent, at last in part, on reduced levels of circulating anaphylactic antibodies, as detected by passive cutaneous anaphylaxis test, and by consequent reduced ability of mast cell desgranulation, evidenced by in vitro trachea contraction. Together, our data show that HQ and PHE exposure differently affect the specific and non-specific ínflammatory reactions.

No description available.

: Methamphetamine-related deaths have been rising along with those involving synthetic opioids, mostly fentanyl and fentanyl analogs (FAs). However, the extent to which methamphetamine involvement in deaths differs from those changes occurring in synthetic opioid involvement is unknown.: To determine the patterns and temporal changes in methamphetamine-related deaths with and without other drug involvement.: Data from all methamphetamine-related deaths in West Virginia from 2013 to 2018 were analyzed. Quasi-Poisson regression analyses over time were conducted to compare the rates of change in death counts among methamphetamine and fentanyl//FA subgroups.: A total of 815 methamphetamine-related deaths were analyzed; 572 (70.2%) were male and 527 (64.7%) involved an opioid. The proportion of methamphetamine only deaths stayed relatively flat over time although the actual numbers of deaths increased. Combined fentanyl/FAs and methamphetamine were involved in 337 deaths (41.3%) and constituted the largest increase from 2013 to 2018. The modeling of monthly death counts in 2017-2018 found that the average number of deaths involving fentanyl without methamphetamine significantly declined (rate of change -0.025, < .001), while concomitant fentanyl with methamphetamine and methamphetamine only death counts increased significantly (rate of change 0.056 and 0.057, respectively, < .001).: Fentanyl and FAs played an increasingly significant role in methamphetamine-related deaths. The accelerating number of deaths involving fentanyl/FAs and methamphetamine indicates the importance of stimulants and opioids in unintentional deaths. Comprehensive surveillance efforts should continue to track substance use patterns to ensure that appropriate prevention programs are undertaken.

The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

<p>Genetically determined differences in drug metabolism and disposition and drug targets play a pivotal role in the interindividual variability in the clinical outcome of antipsychotic treatment. The aim of this thesis was to study the impact of polymorphisms in genes involved in the pharmacokinetics and pharmacodynamics of antipsychotics, with special focus on their extrapyramidal and metabolic adverse effects. </p><p>Polymorphisms in serotonin 2A and 2C receptor coding genes (<i>HTR2A</i> and <i>HTR2C</i>) were found to be associated with the risk to develop extrapyramidal side effects (EPS) in patients on short term perphenazine treatment. A further study in a larger group of patients on long term treatment with various classical antipsychotics confirmed the association between occurrence of EPS and <i>HTR2C</i> polymorphisms. In another study, dose corrected steady state serum clozapine and N-desmethylclozapine concentrations (C/D) and insulin elevation during clozapine therapy were found to correlate with <i>CYP1A2</i> but not with <i>CYP2D6</i> polymorphisms. Furthermore, <i>HTR2C</i> and <i>HTR2A</i> polymorphisms were found to have significant influences on BMI and C-peptide levels in patients treated with olanzapine and clozapine. Evaluation of the impact of polymorphisms in genes encoding CYP3A4, CYP3A5 and P-glycoprotein (<i>ABCB1</i>) in addition to CYP2D6 on the steady state plasma levels of risperidone, 9-hydroxyrisperidone and their active moiety revealed a significant influence of <i>ABCB1 </i>genotype on 9-hydroxyrisperidone and active moiety C/Ds, while <i>CYP2D6</i> genotype associated with risperidone C/Ds but not with 9-hydroxyrisperidone or active moiety C/D. </p><p>We have shown that polymorphisms in genes involved in the pharmacokinetics and the pharmacodynamics of antipsychotic drugs play a role in the occurrence of adverse effects, both EPS and metabolic disturbances, induced by antipsychotic treatment. Genotyping for <i>HTR2A</i>, <i>HTR2C</i>, <i>CYP1A2</i>, <i>CYP2D6</i> and <i>ABCB1</i> polymorphisms may therefore potentially provide useful information to identify patients at higher risk to develop EPS or metabolic adverse during schizophrenia treatment with antipsychotic drugs.</p>

Introduction: Alcohol is an indirect contributor to HIV transmission in sub-Saharan Africa. Alcohol users in general, and heavy, episodic drinkers in particular, are more likely to engage in risky sexual behaviour. Interventions promoting the reduction of alcohol use in conjunction with sex are likely to enhance the HIV prevention response. However, little is known about the relationship between different dimensions of alcohol use and risky sexual behaviour in the general adult population in South Africa. The overall aim of this study was to examine the relationship between alcohol dependence, binge drinking and frequency of drinking in the past month and risky sexual behaviour among males and females aged 16-55 years in South Africa in 2012. Methods: This was a secondary analysis of data from a nationally representative cross-sectional study of males and females aged 16-55 years in 2012. Bivariate and multivariate analysis was conducted to investigate the relationship between alcohol use and risky sexual behaviour. Three nuanced measures of alcohol use were used – alcohol dependence, binge drinking, and frequency of drinking in the past month. The outcomes examined included multiple sexual partners (MSP) in the past 12 months, MSP in the past month, transactional sex, age-disparate sex and condom use at last sex. Results: Some 10,034 respondents (n=4,065 males and n=5,969 females) were interviewed. This study found that for males, there was no significant relationship between alcohol dependence and risky sexual behaviour. For females, those who were alcohol dependent were more likely to have received money/gifts in exchange for sex. Binge drinking and frequency of drinking in the past month were associated with risky sexual behaviour for both males and females. For males, binge drinking was associated with: MSP in the past 12 months (AOR: 1.93, 95% CI 1.37 - 2.72), providing gifts/money in exchange for sex (AOR: 1.53, 95% CI 1.01 - 2.33), and having a sexual partner five or more years younger than themselves (AOR 1.44, 95% CI 1.09 - 1.89). An interaction between binge drinking and self-efficacy for resisting MSP was positively associated with MSP in the past month. Frequency of drinking in the previous month was associated with all five outcome variables and a dose response relationship was present. An interaction between frequency of drinking and self-efficacy for resisting MSP was positively associated with MSP in the past month. For females, binge drinking was associated with: MSP in the past 12 months (AOR 1.93, 95% CI 1.37-2.72), MSP in the past month (AOR 1.79, 95% CI: 1.03 - 3.10), and receiving money/gifts in exchange for sex (AOR 3.10, 95% CI 1.45 - 6.62). An interaction between binge drinking and self-efficacy for resisting MSP was positively associated with MSP in the 12 past months. Frequency of drinking was associated with MSP in the past month. A dose response relationship was evident with females who drank more frequently in the past month being more likely to have had MSP in the past 12 months. This study found high levels of non-drinking (62.80%) but high levels of hazardous drinking among those who drank. Males were more likely to drink and to display hazardous drinking patterns. In general males were more likely to engage in risky sexual behaviour, although males were more likely to have used a condom at last sex. Conclusions: Overall this study has described the patterns and prevalence of alcohol use and risky sexual behaviour in the general population in South Africa. It has demonstrated gender-specific relationships between various types of alcohol use and risky sexual behaviour and has new insights into the complex relationship between these two phenomena. Results suggest that the drinking environment facilitates high-risk sexual encounters. Findings from this study can be used to design and implement future interventions to address this important risk factor for HIV.

Chan Mok-wah, Paul. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves [219-231]). / ACKNOWLEDGEMENTS / SUMMARY / LIST OF ABBREVIATIONS / Chapter CHAPTER 1. --- INTRODUCTION / Chapter 1.1 --- HISTORY --- p.1 / Chapter 1.2 --- RADIATION EXPOSURES OF THE POPULATION --- p.1 / Chapter 1.2.1 --- Introduction --- p.1 / Chapter 1.2.1 --- The Projected Expansion of Medical Exposures --- p.2 / Chapter 1.3 --- RADIATION HAZARDS --- p.6 / Chapter 1.3.1 --- Deterministic Effects --- p.6 / Chapter 1.3.2 --- Stochastic Effects --- p.7 / Chapter 1.3.3 --- Pre-natal Irradiation --- p.9 / Chapter 1.4 --- THE LOCAL SITUATION --- p.9 / Chapter 1.5 --- JUSTIFICATION OF THE STUDY OF LOCAL PATIENT DOSE --- p.10 / Chapter CHAPTER 2. --- THE MEDICAL EXPOSURES IN HONG KONG / Chapter 2.1 --- INTRODUCTION --- p.11 / Chapter 2.2 --- MAN-MADE RADIATION IN HONG KONG --- p.11 / Chapter 2.2.1 --- Occupational Exposure --- p.11 / Chapter 2.2.2 --- Radioactive Fall-out --- p.12 / Chapter 2.2.3 --- Nuclear Medicine --- p.12 / Chapter 2.2.4 --- Diagnostic Radiology --- p.12 / Chapter 2.3 --- THE FUTURE TREND --- p.13 / Chapter 2.4 --- THE CURRENT STUDY --- p.15 / Chapter CHAPTER 3. --- METHODS OF OPTIMISATION / Chapter 3.1 --- INTRODUCTION --- p.17 / Chapter 3.2 --- JUSTIFICATION OF DIAGNOSTIC RADIATION EXPOSURE --- p.17 / Chapter 3.3 --- OPTIMISATION OF DIAGNOSTIC RADIATION EXPOSURE --- p.18 / Chapter 3.4 --- THE CONTROL OF EXPOSURES --- p.19 / Chapter 3.4.1 --- The Control of Occupational Exposure --- p.19 / Chapter 3.4.2 --- The Control of Public Exposure --- p.20 / Chapter 3.4.3 --- The Control of Patient Exposure --- p.20 / Chapter 3.5 --- A PRACTICAL APPROACH TO CONTROL PATIENT EXPOSURES --- p.23 / Chapter 3.5.1 --- Intrumental Approach --- p.23 / Chapter 3.5.2 --- Technical Approach --- p.24 / Chapter 3.5.3 --- Administrative Approach --- p.25 / Chapter 3.6 --- CONCLUSION --- p.26 / Chapter CHAPTER 4. --- METHOD OF STUDY / Chapter 4.1 --- INTRODUCTION --- p.27 / Chapter 4.2 --- A WORKING SCHEME --- p.27 / Chapter 4.3 --- THE MEASUREMENT OF ESD --- p.29 / Chapter 4.3.1 --- Thermoluminescent Dosimetry --- p.29 / Chapter 4.3.2 --- The TL Material Adopted --- p.30 / Chapter 4.3.3 --- Irradiated of TLDs --- p.32 / Chapter 4.3.4 --- Readout of the Exposed TLDs --- p.32 / Chapter 4.3.5 --- Accuracy of Readings --- p.35 / Chapter 4.4 --- MONTE CARLO SIMULATION --- p.36 / Chapter 4.4.1 --- Introduction --- p.36 / Chapter 4.4.2 --- History --- p.38 / Chapter 4.4.3 --- The Principle --- p.38 / Chapter 4.4.4 --- Photon History --- p.40 / Chapter 4.4.5 --- The Use of Monte Carlo simulation in Organ Doses Estimation --- p.47 / Chapter 4.4.6 --- The Electron-Gamma-Shower (EGS4) Code System --- p.51 / Chapter 4.5 --- A LOCAL MATHEMATICAL PHANTOM --- p.52 / Chapter 4.5.1 --- Introduction --- p.52 / Chapter 4.5.2 --- An Ideal Mathematical Phantom --- p.52 / Chapter 4.5.3 --- Choice of Mathematical Phantom Model --- p.53 / Chapter 4.5.4 --- The Development of a Chinese Mathematical Phantom --- p.55 / Chapter 4.5.5 --- Results --- p.56 / Chapter 4.5.6 --- A Comparison --- p.60 / Chapter 4.6 --- A SUMMARY --- p.62 / Chapter CHAPTER 5. --- POPULATION STUDIES / Chapter 5.1 --- INTRODUCTION --- p.63 / Chapter 5.2 --- FREQUENCY SURVEY --- p.63 / Chapter 5.2.1 --- Survey in Private Sectors --- p.63 / Chapter 5.2.2 --- Surveyin Government Sectors --- p.64 / Chapter 5.3 --- DOSE SURVEY --- p.66 / Chapter 5.3.1 --- Selection of Regions and Projections --- p.66 / Chapter 5.3.2 --- Selection of Hospitals and Laboratories --- p.66 / Chapter 5.4 --- SAMPLE SIZE --- p.67 / Chapter CHAPTER 6. --- RESULTS / Chapter 6.1 --- INTRODUCTION --- p.68 / Chapter 6.2 --- SAMPLE SIZE --- p.68 / Chapter 6.3 --- AGE BAND AND SEX DISTRIBUTION --- p.68 / Chapter 6.4 --- THE MEASURED ESD --- p.75 / Chapter 6.4.1 --- Histograms of ESDs by Projection --- p.75 / Chapter 6.4.2 --- A Comparison of ESDs by Projection --- p.89 / Chapter 6.4.3 --- A Comparison of ESDs by Centre --- p.93 / Chapter 6.4.4 --- A Comparison of Collective ESDs by Centre --- p.96 / Chapter 6.5 --- THE ESTIMATED ORGAN DOSES --- p.103 / Chapter 6.5.1 --- Introduction --- p.103 / Chapter 6.5.2 --- Method --- p.103 / Chapter 6.5.3 --- Normalised Organ Doses --- p.105 / Chapter 6.5.4 --- Organ doses per Projection --- p.105 / Chapter 6.5.5 --- A Computerised programme --- p.119 / Chapter 6.6 --- A COMPARISON OF ORGAN DOSES ESTIMATED ON LOCAL AND NRPB MODELS --- p.152 / Chapter CHAPTER 7. --- SOURCES OF UNCERTAINTY / Chapter 7.1 --- UNCERTAINTITIES IN COMPUTATION --- p.156 / Chapter 7.1.1 --- Inaccuracy of the Justaposition of Complex Human Anatomy and the X-ray Beam --- p.156 / Chapter 7.1.2 --- Statistical Uncertainties --- p.156 / Chapter 7.1.3 --- Attenuation Coefficient Uncertainties --- p.157 / Chapter 7.1.4 --- Anatomic Inexactitudes --- p.157 / Chapter 7.2 --- ERRORS CONTRIBUTED BY TLDs --- p.155 / Chapter 7.3 --- TOTAL POSSIBLE ERROR --- p.157 / Chapter 7.4 --- VERIFICATION OF THE RESULTS --- p.158 / Chapter 7.4.1 --- Verification of the Measured ESD --- p.158 / Chapter 7.4.2 --- Verification of the Estimated Organ Doses --- p.158 / Chapter CHAPTER 8. --- HEALTH IMPLICATIONS / Chapter 8.1 --- INTRODUCTION --- p.161 / Chapter 8.2 --- DATA SOURCE --- p.161 / Chapter 8.3 --- ASSUMPTIONS --- p.162 / Chapter 8.4 --- SOMATIC RISK --- p.162 / Chapter 8.4.1 --- Somatically Significant Dose (SSD) --- p.162 / Chapter 8.4.2 --- Results --- p.163 / Chapter 8.5 --- LEUKAEMIC RISK --- p.166 / Chapter 8.5.1 --- Leukaemically Significant Dose (LSD) --- p.166 / Chapter 8.5.2 --- Results --- p.167 / Chapter 8.6 --- GENETIC RISK --- p.170 / Chapter 8.6.1 --- Genetically Significant Dose (GSD) --- p.170 / Chapter 8.6.2 --- Results --- p.171 / Chapter 8.7 --- DISCUSSION --- p.174 / Chapter CHAPTER 9. --- DISCUSSION --- p.199 / Chapter 9.1 --- MEAN ESDs PER PROJECTION --- p.199 / Chapter 9.2 --- A COMPARISON OF MEAN ESDs BETWEEN LOCAL CENTRES --- p.200 / Chapter 9.3 --- A COMPARISON OF MEAN ESDs BETWEEN COUNTRIES --- p.202 / Chapter 9.4 --- EFFECTIVE DOSE PER EXAMINATION --- p.203 / Chapter 9.5 --- NEED FOR LOCAL ANTHROPOMORPHIC PHANTOM --- p.204 / Chapter 9.6 --- ORGAN DOSES WITH HIGH CANCER INDUCTION --- p.205 / Chapter 9.7 --- A DISTRIBUTION OF COLLECTIVE DOSES --- p.206 / Chapter 9.8 --- "A DISTRIBUTION OF SSD, LSD AND GSD" --- p.209 / Chapter 9.9 --- OVERALL RISK ESTIMATION --- p.212 / Chapter 9.10 --- POPULATION ORGAN DOSES --- p.213 / Chapter 9.11 --- SUMMARY --- p.214 / Chapter CHAPTER 10. --- CONCLUSION --- p.217 / REFERENCES --- p.R 1 - 12 / APPENDICES / Chapter A. --- RADIATION QUANTITIES USED IN PATIENT DOSIMETRY --- p.A 1 - 12 / Chapter B. --- QUALITY ASSURANCE --- p.B 1 - 14 / Chapter C. --- DOSE REDUCTION --- p.C 1 - 11 / Chapter D. --- REJECT ANALYSIS --- p.D 1 - 15 / Chapter E. --- PUBLISHED WORK IN DOSE MEASUREMENT --- p.E 1 - 18 / Chapter F. --- THERMOLUMINESCENT DOSIMETRY --- p.F 1 - 27 / Chapter G. --- A STUDY ON ANTHROPOMORPHIC PHANTOM --- p.G 1 - 4

by Lo Ping Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1987. / Includes bibliographical references.

by Josephine Wing Sze Lau. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 84-112). / Abstracts in English and Chinese. / Acknowledgment --- p.iii / Abstract --- p.iv / List of Abbreviations --- p.viii / Chapter CHAPTER ONE: --- INTRODUCTION / Chapter 1.1 --- Methamphetamine (METH) --- p.1 / Chapter 1.1.1 --- Historical Background and Epidemiology --- p.1 / Chapter 1.1.2 --- Physical Effects of METH --- p.4 / Chapter 1.1.3 --- Neurochemical Alternation of METH --- p.6 / Chapter 1.2 --- Mechanisms of METH Toxicity / Chapter 1.2.1 --- Oxidative Stress --- p.8 / Chapter 1.2.1.1 --- Superoxide (O2-) and Superoxide Dismutase (SOD) --- p.10 / Chapter 1.2.1.2 --- "Hydrogen Peroxide (H202), Catalase and Glutathione (GSH)" --- p.11 / Chapter 1.2.1.3 --- Hydroxyl Radical (OH.) --- p.12 / Chapter 1.2.1.4 --- Nitric Oxide (NO) --- p.13 / Chapter 1.2.2 --- Apoptosis --- p.16 / Chapter 1.2.3 --- Excitotoxicity --- p.17 / Chapter 1.2.4 --- Mitochondrial Dysfunction --- p.18 / Chapter 1.2.5 --- Hyperthermia --- p.21 / Chapter 1.2.5.1 --- Cyclooxygenase-2 (COX-2) --- p.23 / Chapter 1.2.5.2 --- Heme-oxygenase-1 (HO-1) --- p.25 / Chapter 1.2.5.3 --- The Effects of Nitric Oxide (NO) on COX-2 and HO-1 Expressions --- p.27 / Chapter 1.3 --- Astrocytes / Chapter 1.3.1 --- Characteristics of Astrocytes --- p.29 / Chapter 1.3.2 --- Astrocyte Functions --- p.30 / Chapter 1.3.3 --- The Role of Astrocytes in METH-induced Neurotoxicity --- p.34 / Chapter 1.4 --- Aim of Project --- p.37 / Chapter CHAPTER TWO: --- MATERIALS AND METHODS / Chapter 2.1 --- Cell Cultures / Chapter 2.1.1 --- Astrocyte Cultures --- p.42 / Chapter 2.1.2 --- CATH.a Cell line and Astrocytes Co-cultures --- p.43 / Chapter 2.2 --- Treatment / Chapter 2.2.1 --- METH Treatment --- p.44 / Chapter 2.2.2 --- Inhibition of Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS) --- p.44 / Chapter 2.3 --- Lactate Dehydrogenase (LDH) Assay --- p.45 / Chapter 2.4 --- Assay for Reactive Oxygen Species (ROS) Formation --- p.47 / Chapter 2.5 --- Assay for Adenosine Triphosphate (ATP) Content --- p.48 / Chapter 2.6 --- Determination of Mitochondrial Membrane Potential (Δ Ψm) --- p.50 / Chapter 2.7 --- Determination of Nitrite Levels in Cultured Astrocytes --- p.51 / Chapter 2.8 --- Western Blot Analysis --- p.52 / Chapter 2.8.1 --- COX-2 --- p.53 / Chapter 2.8.2 --- HO-1 --- p.53 / Chapter 2.9 --- Viability Assay of CATH.a-Astrocyte Cocultures --- p.54 / Chapter 2.10 --- Statistics --- p.55 / Chapter CHAPTER THREE: --- RESULTS / Chapter 3.1 --- The Effects of METH Treatment on Cultured Astrocytes / Chapter 3.1.1 --- Lactate Dehydrogenase (LDH) Activities --- p.56 / Chapter 3.1.2 --- Morphological Changes --- p.56 / Chapter 3.1.3 --- The Production of Reactive Oxygen Species / Chapter 3.1.3.1 --- Rate of change (0-120 min) --- p.57 / Chapter 3.1.3.2 --- Time course (0 - 48 h) --- p.57 / Chapter 3.1.4 --- Change in ATP Content --- p.58 / Chapter 3.1.5 --- Change in Mitochondrial Membrane Potential (Δ Ψm) --- p.59 / Chapter 3.1.6 --- Nitrite levels after METH treatment / Chapter a) --- Striatal astrocytes --- p.59 / Chapter b) --- Mesencephalic astrocytes --- p.60 / Chapter c) --- Cortical astrocytes --- p.60 / Chapter 3.1.7 --- The Effects of Aminoguanidine (AG) on Nitrite Levels / Chapter a) --- Striatal astrocytes --- p.61 / Chapter b) --- Mesencephalic astrocytes --- p.62 / Chapter c) --- Cortical astrocytes --- p.62 / Chapter 3.1.8 --- The Effects of Indomethacin (INDO) on Nitrite Levels / Chapter a) --- Striatal astrocytes --- p.63 / Chapter b) --- Mesencephalic astrocytes --- p.64 / Chapter c) --- Cortical astrocytes --- p.64 / Chapter 3.1.9 --- Change in Cyclooxygenase-2 (COX-2) Protein Levels / Chapter a) --- Striatal astrocytes --- p.65 / Chapter b) --- Mesencephalic astrocytes --- p.65 / Chapter c) --- Cortical astrocytes --- p.66 / Chapter 3.1.10 --- Change in Heme-oxygenase-1 (HO-1) Protein Levels / Chapter a) --- Striatal astrocytes --- p.66 / Chapter b) --- Mesencephalic astrocytes --- p.66 / Chapter c) --- Cortical astrocytes --- p.67 / Chapter 3.2 --- Cell Viability on CATH.a-Astrocyte Cocultures After METH Treatment --- p.67 / Chapter CHAPTER FOUR: --- DISCUSSION AND CONCLUSION --- p.69 / REFERENCES --- p.84