Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 176-193). Also available on the Internet.

Thesis--University of Helsinki. / Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 176-193). Also available on the Internet.

Objective The study is to explore the relationship between antipsychotics and blood glucose level or lipid level of patients with mental illness in psychiatric outpatient clinic of Queen Mary Hospital. Participants and Methods Case reviews through Clinical Management System were carried out. Total 108 psychotic cases involved in the study. 24 were excluded as the patients did not have any treatment of antipsychotics. 84 patients were qualified for review. 40 females and 68 males involved. Their ages are between 13 and 68. Patients’ demographics information, blood glucose level or lipid level were retrieved. Some important findings are also noted. Data collection carried in May 2014. Results There are no significant changes in fasting blood glucose or lipid level for either typical or atypical antipsychotics. We found that the frequency of checking blood glucose or lipid level was too low and not regular. Risperidone and Olanzapine are the most commonly used in this psychiatric outpatient clinic. Moreover, 9 cases change from psychosis to Paranoid type schizophrenia. The most frequent diagnosis in the clinic is Paranoid type schizophrenia. 36 cases, one third of the samples, are diagnosed as Paranoid type schizophrenia. Conclusions Although we cannot conclude the effect of antipsychotics on blood glucose level or lipid level of patients with mental illness, there is an increasing concern about antipsychotics leading to metabolic problems through the case reviews. We suggest that routine physical health screening, guidelines setting up, predictors should be carried out in the clinic. / published_or_final_version / Psychological Medicine / Master / Master of Psychological Medicine

A series of sulfonate anionic lipids esters derived from 4-sulfobenzoic acid (single chain) or 5-sulfoisophthalic acid (double chain) with chain length from C14 to C18 were synthesized and characterized. The sodium salts were uniformly insoluble in ethanol; the tetramethylammonium salts of the single chain derivative from oleyl alcohol and the double chain derivative from 2-octyldodecan-1-ol were sufficiently soluble for subsequent experiments. Lipids in ethanol and aqueous buffers were mixed in a microfluidic system (NanoAssmblr ® microfluidic mixer) to prepare a lipid dispersion containing vesicles and/or nanoparticles. Initial studies on prediction and controlling vesicle size based on lipid geometric parameters showed that particle size could be successfully affected and controlled by altering lipid compositions consistent with the formation of vesicles. A survey using high resolution cryo-Scanning Transmission Electron microscopy of the sample made by the microfluidic mixer demonstrated that vesicles were formed but a majority of the sample reformed to other aggregates, which complicated the interpretation of the initial product distribution. Further investigation on the efficiency of incorporation of phospholipids into vesicles indicated that 55% of the initial phospholipid appeared in the vesicle fractions. Sulfonate anionic lipids are incorporated into vesicles with lower efficiency and reach a threshold beyond which the sulfonate lipid is not incorporated. Entrapment efficiency was studied with three dyes. Different concentrations of the hydrophobic neutral dye Nile red, the hydrophilic cationic dye neutral red and the hydrophilic anionic dye hydroxypyrene trisulfonate (HPTS) were prepared. The entrapment efficiency was quantitatively analyzed by HPLC, and electrospray mass spectrometry; up to 15% of the initial dye present could be entrapped. Vesicles permeability assays using the ion channel gramicidin and the ion carrier valinomycin with HPTS-loaded vesicle samples showed that vesicle samples made by the microfluidic mixer and made by a conventional extrusion method appeared to behave in the same manner. Addition of a sulfonate anionic lipid to the lipid mixture resulted in vesicle leakage. The unilamellar proportion of HPTS loaded vesicle samples was assessed using a mellitin assay. A vesicle sample made by the microfluidic mixer was 80% unilamellar; a vesicle sample made by the extrusion method on the same lipid mixture was 60% unilamellar. / Graduate / mengxiuzheng@gmail.com

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Pharmacology / Master / Master of Philosophy

No description available.

Bioactivation of organohalogen xenobiotics produces reactive intermediates which alkylate macromolecules. The activation of carbon tetrachloride, trichloroethylene, and methylene chloride was studied in isolated rat hepatocytes by examining alkylation of lipid, protein, RNA, and DNA. All organohalogens alkylated lipid and protein. Carbon tetrachloride and trichloroethylene, but not methylene chloride, alkylated RNA and DNA. Methylene chloride was more highly activated in an oxygen containing atmosphere by hepatocytes, consistent with a proposed formation of formyl chloride as its reactive intermediate. Trichloroethylene was also shown to be more highly activated in an oxygen containing atmosphere, consistent with a proposed trichloroethylene epoxide reactive intermediate. Carbon tetrachloride was shown to be more highly activated in an oxygen-free atmosphere, consistent with a proposed trichloromethyl free radical reactive intermediate. Hepatocytes from rats pretreated with phenobarbital to induce cytochrome P-450 mixed function oxidase activated carbon tetrachloride and trichloroethylene to alkylating intermediates greater than did hepatocytes from non-induced rats. The interaction of carbon tetrachloride metabolites with fatty acids was studied in a chemical activation model system. The thermal decomposition of benzoyl peroxide produced free radicals which activated carbon tetrachloride. The resulting trichloromethyl free radicals abstracted a hydrogen from methyl stearate resulting in chloroform and fatty acid free radicals. Using chemical ionization mass spectrometry, it was discovered that the fatty acid free radical abstracted a chlorine from carbon tetrachloride resulting in chlorinated fatty acid esters. When methyl oleate was used as a substrate in the benzoyl peroxide model system, it was discovered that the trichloromethyl free radical binds covalently, resulting in a fatty acid adduct radical. This radical then abstracted a chlorine to produce chloro, trichloromethyl stearic acid methyl ester, identified by chemical ionization mass spectrometry. Carbon tetrachloride radiolabeled with ¹⁴C or ³⁶Cl in dual label binding experiments in the benzoyl peroxide model system confirmed the mass spectral data. Methyl stearate bound ³⁶Cl- and ¹⁴C-carbon tetrachloride in the ratio of approximately 10 to 1, whereas methyl oleate bound in the ratio of approximately 3.5 to 1. The existence of fatty acid radicals due to hydrogen abstraction or covalent binding by trichloromethyl free radicals was demonstrated in microsomal preparations. In the presence of tritiated water and ¹⁴C-carbon tetrachloride, dual-label analysis demonstrated that the tritium incorporation into microsomal lipids approximately equalled the sum of carbon tetrachloride metabolites bound covalently to microsomal lipids and chloroform production.

These studies investigated the plasma lipid profile of endurance athletes and their ability to clear intravascular triglycerides (TG). Study I was a cross-sectional determination of the relationship between cholesterol fractions and weekly running mileage. Study II examined the relationships between the changes in total and HDL-cholesterol (HDL-C) and body composition during a training program. Study III employed an intravenous fat tolerance test (IVFTT) and a post-heparin TG clearance to indirectly assess lipoprotein lipase activity in three different training groups. Finally, Study IV examined the effects of a 12-week training program on TG clearance in trained subjects. In Study I there were significant correlations between HDL-C and percent body fat (r = -0.36, p < .001) and miles run per week (r = 0.50, p < .001), the latter relationship remaining significant when statistically adjusted for age, alcohol consumption, or relative body composition. With the increased weekly running mileage in Study II, HDL-C increased by 5.0 mg/dl (p < .01), and total cholesterol remained unchanged. All components of body composition changed significantly, but only the change in lean weight significantly correlated with the change in HDL-C (r = 0.46, p < .025). In Study III the rate of Intralipid clearance correlated with fat weight (r = -0.66, p < .001), fasting TG (r = -0.39, p < .05), and V̇O₂ max (r = 0.64, p < .001). The heparin-induced fractional clearance of TG's correlated to V̇O₂ max (r = -0.51, p < .01) and fat weight (r = 0.47, p < .01). While the runners and the untrained subjects were similar in body composition and lipid profile, when divided into groups, the elite runners were leaner, had higher HDL-C (p < .05), and were able to clear Intralipid (p < .01) and plasma TG's (p < .05) faster than the other groups. There was a trend towards a more favorable lipidprofile and enhanced TG clearance in Study IV, but only V̇O₂ max (p < .05) and post-heparin fractional clearance of TG's (p < .05)improved significantly. These data suggest that endurance trained subjects have higher HDL-C, lower TG, and an enhanced capacity to clear the intravascular compartment of TG's. These changes cannot be explained solely by the body composition or diets of the athletes and must be due in part to changes evoked by their chronic training.