These (Ph.D.)--University of Massachuesetts Lowell, 2008. / Title from PDF title page. Available through UMI ProQuest Digital Dissertations. Includes bibliographical references (leaves 55-66). Also issued in print.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2002. / Includes bibliographical references. Also available in electronic version. Access restricted to campus users.

Thesis (M.S.)--University of North Carolina at Wilmington, 2006. / Includes bibliographical references (leaves: 61-66)

The literature relating to the ontogeny of the opioid system and to the toxic effects of lead in both man and animals with particular reference to neurochemical and behavioural toxicity of lead is reviewed. The effects of perinatal lead exposure on the development of several aspects of opioid function has been studied using a dosing model of lead (as the acetate) in the maternal drinking water from conception until postnatal day 14 or 21. This model of low level perinatal lead exposure in rats had no toxic effects on growth and produced blood lead levels close to the safety limits set for human exposure and similar to those that have been recorded in some children. The ontogeny of morphine antinociception using the tail immersion test and ketocyclazocine in the paw pressure test was studied in 10,21 and 30 day old rats. Perinatal lead exposure decreased the antinociceptive activity of both morphine and ketocyclazocine in 10 day old rats. Recovery of morphine antinociception occured by 21 days and ketocyclazocine antinociception by 30 days. Radioligand binding studies with [3H]DAGO were used to study the ontogeny of u-opioid receptors in 10,21 and 30 day old rats. Perinatal lead exposure was without effect on equilibrium dissociation constant or maximal binding capacity. Radioligand binding studies with [[3]H] DPDPE were used to study the ontogeny of 6 -opioid receptors in rats between 15 and 50 days. The affinity of the 6-opioid binding site for [[3]H] DPDPE was reduced by perinatal lead exposure but without accompanying changes in binding capacity. This effect of lead on s-opioid receptors was persistant and was observed in rats aged 15-50 days. Basal plasma corticosterone levels (measured fluorimetrically) were elevated by perinatal lead exposure in 45 and 60 day old rats but not in 30 day old rats. In addition the modulatory effect of morphine on stress induced elevations of corticosterone levels was also affected by lead exposure. A reduced effect of morphine was seen in 30 day old animals whilst an increased effect was seen in 60 day old animals. Locomotor activity (measured by photocell detection) of 10,21 and 30 day old rats was recorded over 1 hour during the dark phase of the light/dark cycle. Exploratory locomotor activity was reduced in lead exposed animals at postnatal day 10 and the hypolocomotor effect of morphine was also increased in 10 day old lead exposed animals. The opioid system is particularly sensitive to perinatal low level lead exposure and this is manifested in several aspects of physiological function. Possible mechanisms by which lead affects the development of the opioid system are discussed.

No abstract available Please read the resumé in the section 08back of this document / Thesis (PhD)--University of Pretoria, 2009. / Microbiology and Plant Pathology / unrestricted

No description available.

Toxic shock syndrome toxin-1 (TSST-1), an exoprotein produced by some strains of Staphylococcus aureus, is implicated in the pathogenesis of menstrual TSS. However, its role in nonmenstrual TSS is less certain. In order to study the pathogenetic role of TSST-1 in TSS, three approaches were taken: a) to develop an ELISA for detection of TSST-1 in biologic fluids in order to verify TSST-1 production in vivo in TSS patients, b) to quantitate TSST-1 specific antibodies in the serum of TSS patients and controls to determine whether such antibodies are protective, and c) to attempt to identify other staphylococcal products which may be implicated in some forms of TSS. A sensitive and specific noncompetitive enzyme-linked immunosorbent assay (ELISA) capable of detecting TSST-1 at concentrations from 0.5 to 16 ng/ml was developed. This assay did not detect other staphylococcal enterotoxins including A, B, C₁, C₂, C₃, D and E. Possible interference by protein A was readily eliminated by pretreatment of test samples with 10% nonimmune rabbit serum. The assay was adapted for rapid screening of TSST-1 production by S. aureus isolates in culture supernatants in vitro, and for the detection of TSST-1 in vaginal washings and urine of TSS patients and healthy controls in vivo. All 35 S. aureus isolates confirmed to be TSST-1 positive by Ouchterlony immunodiffusion, and 59 of 60 isolates confirmed to be TSST-1 negative, gave concordant results by ELISA. Interestingly, toxigenic S. aureus strains isolated from TSS patients quantitatively produced significantly more toxin in vitro compared to toxigenic control strains (p<0.05, Mann-Whitney rank sum test). TSST-1 could be detected by ELISA in 3 of 4 vaginal washings collected within 3 days of hospitalization from 3 women with acute menstrual TSS, compared to 0 of 17 washings from 9 TSS women collected greater than 3 days after hospitalization (p=0.003, Fisher's exact test) and 1 of 15 washings from 14 healthy control women (p=0.016). TSST-1 was not detected in the urine of 4 acute TSS patients, 2 convalescent TSS patients or in 3 control urine tested. A sensitive and reproducible ELISA was also developed for the quantitation of TSST-1 specific IgG in serum. Anti-TSST-1 was assessed in acute and convalescent sera from 16 nonmenstrual (9 female, 7 male) and 14 menstrual TSS patients, and from 87 healthy women and 66 healthy men as controls. Quantitative levels of anti-TSST-1 in the study groups were calculated as the percent of standard activity (POSA) relative to a medium titre reference serum standard. ELISA titers in acute sera from menstrual TSS (26.2 ± 5.2, mean POSA ± S.E.M.), but not nonmenstrual TSS women (71.8 ± 18.6), were significantly lower than in healthy controls (78.9 ± 7.3) (p<0.01, Mam-Whitney test). Titers from menstrual TSS patients remained low (25.2 ± 10.7) even during late convalescence (mean duration 20 months after illness onset), compared to healthy female controls (p<0.05). Acute titers in males with TSS (37.0 ± 15.6) were also significantly lower than those in control men (114.6 + 11.0) (p<0.05). An inverse relationship of recovery of toxigenic S. aureus and anti-TSST-1 titers in acute sera of TSS patients was observed. Interestingly, antibody titers in control men were significantly higher than in control women (p<0.001). No age-dependent effects or interactive effects of age and sex on ELISA titers were observed. To enable immunoblot analyses, TSST-1 was produced and partially purified using column chromatography techniques. Percent recovery of TSST-1 from culture supernatant through to the final procedure was approximately 15.5%. The relative purity of TSST-1 (TSST-l/total protein, w/w) was increased from 0.21% in culture supernatants to 94.4% in the final product. Ouchterlony immunoprecipitation against reference rabbit antitoxin demonstrated identity with reference TSST-1 as well as with TSST-1 prepared in other laboratories. Physical characterization demonstrated a molecular weight of 24 kd and a pi of 7.0. Using pooled normal human serum as a first antibody probe, several bands in addition to the 24 kd TSST-1 band were visualized by immunoblot against our partially purified toxin as well as similar preparations obtained from other investigators. To determine whether any of the additional bands might be implicated in TSS, acute and convalescent sera from TSS patients were used to probe for immunoreactive bands in our partially purified TSST-1 as well as a commercially obtained preparation. Seroconversion was demonstrated to the 24 kd TSST-1 protein in 7 of 10 TSS patients from whom toxigenic S. aureus was isolated. In addition, seroconversion was noted to a 49 kd band in 4 patients, to a 21 kd band in 3 patients, to a 28 kd band in 1 patient and to a 32 kd band in 2 patients. In conclusion: 1) the ability to measure TSST-1 in biologic fluids lends stronger support for the role of TSST-1 in menstrual TSS patients; 2) the serologic data support the etiologic role of TSST-1 in menstrual TSS and in nonmenstrual TSS patients from whom toxigenic S. aureus could be cultured, but not for nonmenstrual TSS women from whom toxigenic S. aureus was not isolated; 3) immunoblotting results with acute and convalescent sera from TSS and control patients, not only add further support to the role of TSST-1 in patients from whom toxigenic S. aureus could be isolated, but also indicate that there may be several other staphylococcal products implicated in TSS, particularly in whom antibody to TSST-1 pre-existed in acute sera. The nonresponsiveness or lack of seroconversion to TSST-1 in some patients could suggest either: a) TSST-1 was not the etiologic agent for such patients; b) TSST-1 was the etiologic agent, but the exposure was sufficient for an immune response (similar to tetanus), or; c) some immunologic defect may be present. Future studies are required to clarify these possibilities. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

No description available.

Over the last 20 years, there has occurred an increase in the number, scope, and impact of nanomaterials projects. By leveraging the Surface Plasmon Resonance of metallic nanoparticles for labelling, sensing, and treatment, researchers have demonstrated the versatile utility of these nanomaterials in medicine. The literature provides evidence of use of simple, well-known chemistry for nanomaterials synthesis when the focus is new applications of nanomaterials. A case in point, is the synthesis of metallic nanoparticles, whereby HAuCl4, CuCl2, Cu(acac)2, and AgNO3 are typically employed as nanoparticle precursors. Unfortunately, the use of these precursors limits the number of applications available to these materials - particularly for AuNPs in medicine, where the byproducts of nanoparticle synthesis (most often surface-adsorbed reductants, toxic stabilizers, and growth directors) cause nanoparticles to fail clinical trials. Despite the several thousand publications detailing the advancements in nanoparticle therapeutics, as of 2017, there were only 50 FDA-approved nanoparticle formulations. Less than 10 were based on metallic nanoparticles. This is a problem because many of these nanoparticle therapeutics demonstrate potent cell killing ability and labeling of cells. A solution to this problem may be the use of weakly coordinated, monovalent metal complexes, which require only one electron to reduce them to their metallic state. Further, by designing nanoparticle syntheses around these monovalent complexes, we can employ weaker, environmentally friendly stabilizers. This strategy also forgoes the use of exogenous reducing agents, because the monovalent complexes can be reduced and stabilized by one reagent. Herein we investigate the use of Au(Me2S)Cl, [Cu(MeCN)4]BF4, and AgBF4 with green stabilizers to synthesize a variety of nanomaterials. We find that a range of sizes of spherical particles, as well as a range of sizes of gold triangular prisms can be synthesized by using techniques that follow this strategy.

<p>   </p> <p>Copper (Cu) dyshomeostasis in the brain, especially Cu overload, has been associated with neurodegenerative disorders such as Alzheimer’s disease (AD). Brain Cu levels are partly regulated by the choroid plexus (CP), a tissue that forms a barrier between the blood and cerebrospinal fluid (CSF) and is rich in Cu-transporting proteins. Literature data have shown that ADP-ribosylation factor 1 (ARF1) plays a role in regulating cellular Cu homeostasis; yet its presence and function in the blood-CSF barrier was unknown. The main purpose of the project was to prove the presence of ARF1 in the CP and explore its possible function with regards to Cu regulation. Since the CP is known to accumulate toxic metal lead (Pb) from human and animal studies, the project also aimed to test whether Pb exposure caused CSF Cu dyshomeostasis through disrupting ARF1-mediated Cu regulatory mechanism. Using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), our data clearly demonstrated that ARF1 was highly enriched in the choroidal epithelial Z310 cells and expressed in CP tissues. Acute Pb exposure in mice (one ip. dose at 27 mg Pb/kg followed by tissue dissection 24 hrs later) significantly increased ARF1 expression in the CP as compared to saline-injected controls, suggesting a high responsiveness of the protein to Pb exposure. In the subsequent chronic study, mice were exposed to Pb via drinking water at 200ppm (low-dose) or 800ppm (high-dose) at libitum for 4 weeks (control group had sodium in drinking water). Atomic absorption spectrometry (AAS) analyses verified a dose-dependent Pb accumulation in the CP. Importantly, Cu concentrations in the CSF displayed a Pb dose-dependent increase as compared to controls. IHC data further revealed an altered ARF1 expression in the choroidal epithelia in chronic Pb exposed animals. Further knocking down ARF1 expression in choroidal epithelial Z310 cells using in vitro Arf1-targeting siRNA transfection approach revealed a decreased Cu level in cells, suggesting a critical role of ARF1 in cellular Cu regulation. In choroidal epithelial cells exposed to Pb in culture medium, a down-regulated ARF1 expression partly reversed Pb-induced Cu overload. Taken together, this study provides first-hand evidence to support the presence of ARF1 in the blood-CSF barrier. Further, our data demonstrate that Pb exposure causes Cu overload in the CSF, which is likely mediated by an altered expression of ARF1 in the blood-CSF barrier.</p>