101 |
Manganoporphyrins as adjuvants to enhance pharmacological ascorbate in pancreatic cancer therapyRawal, Malvika 01 December 2013 (has links)
With new insights on mechanism, there is renewed interest in the use of pharmacological ascorbate (AscH-) in cancer therapy. The generation of H2O2 with AscH- acting as an electron donor to O2 is central to AscH- -induced cytotoxicity. We hypothesized that catalytic manganoporphyrins (MnPs) would increase the rate of oxidation of AscH- thereby increasing the flux of H2O2, resulting in increased cytotoxicity. We tested three different MnPs: MnTBAP, MnT2EPyP, and MnT4MPyP, which represent a range of physicochemical and thermodynamic properties. Of the MnPs tested, MnT4MPyP had the greatest effect on increasing the rate of oxidation of AscH-, as seen by the concentration of ascorbate radical [Asc*-] and rate of oxygen consumption. MnPs and AscH-, when combined at concentrations that had minimal effects alone, synergistically increased the cytotoxicity as seen by decreased clonogenic survival in human pancreatic cancer cell lines. Catalase, but not superoxide dismutase, reversed the cytotoxicity of AscH- and MnP, consistent with an H2O2-mediated mechanism. In addition, there was a marked increase in the steady-state concentration of ascorbate radical upon the addition of MnPs to whole blood ex vivo from mice infused with ascorbate as well as from patients treated with pharmacologic ascorbate. The combination of MnT4MPyP with ascorbate inhibited in vivo tumor growth. We conclude that MnPs can increase the rate of oxidation of AscH-, leading to an increased flux of H2O2 resulting in increased ascorbate-induced cytotoxicity
|
102 |
Quantitative Characterization of Free Radical Generation under Ir-192 Photon Irradiation for Gold Nanoparticle Mediated Radiation TherapyXie, Kanru January 2020 (has links)
No description available.
|
103 |
Tocotrienols in Pancreatic Cancer Treatment and PreventionChakraborty, Kanishka, Ramsauer, Victoria Palau, Stone, William, Krishnan, Koyamangalath 01 January 2014 (has links)
Oxidative stress is a documented factor in the pathogenesis of inflammation and cancer. Vitamin E with its antioxidant properties holds promise for use in clinical practice. There are two main forms of vitamin E, tocopherols and tocotrienols. Palm oil contains almost 70% of tocotrienols. Tocotrienols exerts its antiproliferative activity against malignant cells but not on normal cells. Tocotrienols play an important role in counteracting cellular inflammatory response secondary to oxidative stress, thus exerting an anticancer property. Tocotrienols mediate function of NF-kappa B, STAT3 (signal transduction and activators), and COX-2. In addition to its role as an antioxidant and anti-inflammatory agent, tocotrienols also mediate multiple cell cycle pathways. More work needs to be done on animal models and in genetic models of pancreatic cancer to gather more data to eventually consider phase III clinical trial in human subjects.
|
104 |
Prevention of Ischemia/Reperfusion-Induced Cardiac Apoptosis and Injury by Melatonin Is Independent of Glutathione Peroxdiase 1Chen, Zhongyi, Chua, Chu C., Gao, Jinping, Chua, Kao W., Ho, Ye S., Hamdy, Ronald C., Chua, Balvin H.L. 01 March 2009 (has links)
Free-radical generation is one of the primary causes of myocardial ischemia/reperfusion (I/R) injury. Melatonin is an efficient free-radical scavenger and induces the expression of antioxidant enzymes. We have previously shown that melatonin can prevent free-radical-induced myocardial injury. To date, the mechanism underlying melatonin's cardioprotective effect is not clear. In this study, we assessed the ability of melatonin to protect against I/R injury in mice deficient in glutathione peroxidase 1 (Gpx1). Mice hearts were subjected to 40 min of global ischemia in vitro followed by 45 min of reperfusion. Myocardial I/R injury (expressed as % of recovery of left ventricular developed pressure × heart rate) was exacerbated in mice deficient in Gpx1 (51 ± 3% for Gpx1+/+ mice versus 31 ± 6% for Gpx1-/- mice, P < 0.05). Administration of melatonin for 30 min protected against I/R injury in both Gpx1+/+ mice (72 ± 4.8%) and Gpx1-/- mice (63 ± 4.7%). This protection was accompanied by a significant improvement in left ventricular end-diastolic pressure and a twofold decrease in lactate dehydrogenase (LDH) level released from melatonin-treated hearts. In another set of experiments, mice were subjected to 50 min of ligation of the left descending anterior coronary artery in vivo followed by 4 hr of reperfusion. The infarct sizes, expressed as the percentage of the area at risk, were significantly larger in Gpx1-/- mice than in Gpx1+/+ mice (75 ± 9% versus 54 ± 6%, P < 0.05) and were reduced significantly in melatonin-treated mice (31 ± 3.7% Gpx1-/- mice and 33 ± 6.0% Gpx1+/+ mice). In hearts subjected to 30 min of coronary artery occlusion followed by 3 hr of reperfusion, melatonin-treated hearts had significantly fewer in situ oligo ligation-positive myocytes and less protein nitration. Our results demonstrate that the cardioprotective function of melatonin is independent of Gpx1.
|
105 |
Over-Expression of Heat Shock Protein 27 Attenuates Doxorubicin-Induced Cardiac Dysfunction in MiceLiu, Li, Zhang, Xiaojin, Qian, Bo, Min, Xiaoyan, Gao, Xiang, Li, Chuanfu, Cheng, Yunlin, Huang, Jun 01 August 2007 (has links)
Background: Oxidative stress and myocyte apoptosis are thought to play an important role in the pathogenesis, progression and prognosis of heart failure (HF). Heat shock protein 27 (Hsp27) has been found to confer resistance to oxidative stress in cultured cells; however, the role of Hsp27 in in-vivo hearts remains to be determined. Aim: To investigate the effects of Hsp27 over-expression on doxorubicin-induced HF. Methods and Results: Transgenic mice (TG) with cardiac specific over-expression of Hsp27 and their wild type littermates (WT) were challenged with doxorubicin (25 mg/kg, IP) to induce HF. At day 5, TG mice had significantly improved cardiac function and viability and decreased loss of heart weight following doxorubicin exposure compared with WT. In another parallel experiment, doxorubicin-induced increased levels of reactive oxygen species, protein carbonylation, apoptosis and morphologic changes were detected in the mitochondria in WT hearts, whereas these effects were markedly attenuated in TG hearts. In addition, upregulation of heat shock protein 70 and heme oxygenase-1 was present in the TG hearts after doxorubicin stimulation in comparison to WT hearts. Conclusion: These findings indicate that Hsp27 may play a key role in resistance to doxorubicin-induced cardiac dysfunction.
|
106 |
Carbohydrate Mediation of Aqueous Polymerizations: Cyclodextrin Mediation of Aqueous Polymerizations of MethacrylatesMadison, Phillip Holland IV 01 August 2001 (has links)
Cyclodextrin mediation offers a unique mechanism with the potential for interesting control of reaction parameters. Cyclodextrin mediation of hydrophobic monomers may offer desirable kinetics over conventional free radical polymerizations, and it has been shown in this work that cyclodextrin mediation facilitates polymerization of hydrophobic monomers in aqueous solution and in ethylene glycol. It also may be a facile method for controlling relative reactivity of comonomer mixtures. In addition, complexation of cyclodextrin with guest molecules has been utilized in selective synthesis where the host cyclodextrin has been utilized to sterically hinder the attack of certain reactive sites contained within the host cavity. This aspect of inclusion complexation could also be utilized in free radical polymerizations of monomers with multiple reactive double bonds to preferentially reduce the reactivity of the hindered reactive sites.
This thesis involves the use of methylated(1.8)-beta-cyclodextrin (MeCD) as a mediator for polymerizations in solvents that would not facilitate polymerization of the pure monomer in the absence of cyclodextrin. This study focuses on the carbohydrate mediation of a series of methacrylic monomers. t-Butyl methacrylate, n-butyl methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate were complexed with methylated(1.8)-beta-cyclodextrin and subsequently dissolved in either water or ethylene glycol. The complexes were studied by 1H and 13C NMR spectroscopy, thin layer chromatography, CPK modeling, and thermogravimetric analysis, and were found to have molar ratios of cyclodextrin to monomer as high as 1.0 to 0.72. These complexes were then free radically polymerized in either water or ethylene glycol and resulted in high molecular weight polymers that precipitated out of solution, allowing for facile polymer isolation through filtration. Isolated yields were found to be as high as 86 %. The majority of the cyclodextrin remained in solution after polymerization. It was also recovered and found to be recyclable.
Heterogeneous polymerizations were also performed with 2-ethylhexyl methacrylate in which linear dextrin and methylated (1.8)-beta-cyclodextrin were used in emulsifier quantities. It was found that linear dextrin, at concentrations of 3.0 wt% produced a stable latex product with high molecular weight and an isolated yield of >90%. MeCD on the other hand failed to produce a stable emulsion at concentrations between 0.9-3.0 wt%, but remarkably MeCD at 3.0 wt% gave high molecular weight coagulated polymer with a yield of >90%. It is proposed that a heterogeneous mechanism inconsistent with the four major types discussed by Arshady is taking place. Unlike typical suspension or emulsion polymerizations, the cyclodextrin mediated polymerizations are completely homogeneous at the onset, making them more like a dispersion or precipitation polymerization. However, in dispersion and precipitation polymerizations the pure monomer is soluble in the reaction media. In the absence of cyclodextrin, the monomers utilized in this study possessed no appreciable solubility in the reaction media. Therefore, it is proposed that cyclodextrin acts as a phase transfer agent, effectively solublizing the hydrophobic monomer and allowing for the aqueous dispersion or precipitation type polymerization to occur, depending on the relative solubility of the components.
Bulk polymerizations of t-butyl methacrylate, cyclohexyl methacrylate, and 2-ethylhexyl methacrylate and their subsequent use in the preparation of carbohydrate/poly(alkyl methacrylate) blends was also performed in this project. Bulk polymers were utilized as references for physical properties for the polymers produced through polymerization of the MeCD/monomer complexes in either aqueous solution or in ethylene glycol. 1H NMR analysis of the polymers from both the cyclodextrin mediation and bulk polymerizations indicated that the tacticity of the polymers produced in both cases were identical. The bulk polymers were also used in the preparation of carbohydrate/methacrylic blends with potential applications in the areas of selective barriers, biodegradable films. Inclusion of drug molecules or antioxidants into these cyclodextrin containing films also may have potential in drug delivery, or food packaging applications.
In addition, the side chain liquid crystalline monomer, 6-(4-hexyloxy-biphenyl-4-yloxy)hexyl methacrylate was synthesized in high purity via a three-step procedure and confirmed by a combination of mass spectrometry, thin layer chromatography, and 1H and 13C NMR. This hydrophobic liquid crystalline monomer was subsequently complexed with 1.0-3.0 equivalents of methylated(1.8)-beta-cyclodextrin in an attempt to alter the water solubility of the monomer. Complexes of this side-chain liquid crystalline monomer have not been studied previously and it is proposed that complexation with cyclodextrin will lead not only to novel polymerizations routes for this monomer, but also to novel smectic phases for this thermotropic liquid crystalline polymer. / Master of Science
|
107 |
Production of Poly(lactic acid) Biodegradable Films and the Introduction of a Novel Initiation Method for Free Radical Polymerization via Magnetic FieldsMiller, Kent R. 19 July 2012 (has links)
No description available.
|
108 |
The Effect of Acute Exercise on Neutrophils and Oxidative Stress.Quindry, John Carl 01 May 2002 (has links) (PDF)
This study tested the hypothesis that high intensity exercise, independent of total oxygen consumption, results in the most significant elevations in neutrophil (PMN) counts and blood oxidative stress (OS). This study also tested the hypothesis that active individuals have a blunted PMN and OS responses to acute exercise as compared to less active individuals. Nine males (18 – 30 yrs.) participated in 1 maximal (Max) and 3 sub-maximal exercise sessions. The 3 sub-max trials were: 1) LTplus, 45 min. above lactate threshold (LT), 2) LTminus, 45 min. below LT, and 3) LTplusCE, below LT until total oxygen consumption equaled (about 60 min) the LTplus trial. Blood was drawn before and immediately after, 1hr, and 2hr after exercise for measurement of PMN, myeloperoxidase enzyme (MPO), superoxide (O2-), vitamin C (C), urate (U), malondialdehyde (MDA), and lipid hydroperoxides (LPO). Results indicated an intensity-dependent post exercise PMN increase following Max and LTplus (p≤0.05). Post exercise MPO elevations were significant (p≤0.05) and similar for all trials except LTplus (NS). Furthermore, O2- was elevated immediately following Max exercise, while O2-/PMN was not. These data indicate that O2- elevations occur as PMN counts increase. Post-max, C (p=0.009), and U (p=0.034) were depleted indicating a significant reduction in plasma antioxidant fortifications. Subjects were separated according to high (n=5) and low (n=4) activity groups based on physical activity history questionnaires. Low activity subjects had higher PMN following maximal exercise. Pre exercise Low – High group differences neared significance for PMN (p=0.068) and O2- (p=0.09). High activity subjects had higher plasma C levels before and after exercise. Covariate analysis of dietary C intake demonstrated between group differences in plasma vitamin C levels at rest only. These results indicate that maximal intensity exercise resulted in the greatest increase in circulating PMNs and corresponding OS in blood plasma as identified by antioxidant depletion. This study clearly shows that exercise intensity, not total oxygen consumption, plays a role in post exercise neutrophil recruitment, and blood OS. Finally, these results suggest that regular physical activity and increased antioxidant intakes may attenuate the neutrophil rise and OS produced by maximal intensity exercise.
|
109 |
Fundamental Aspects Of Regenerative Cerium Oxide Nanoparticles And Their Applications In NanobiotechnologyPatil, Swanand 01 January 2006 (has links)
Cerium oxide has been used extensively for various applications over the past two decades. The use of cerium oxide nanoparticles is beneficial in present applications and can open avenues for future applications. The present study utilizes the microemulsion technique to synthesize uniformly distributed cerium oxide nanoparticles. The same technique was also used to synthesize cerium oxide nanoparticles doped with trivalent elements (La and Nd). The fundamental study of cerium oxide nanoparticles identified variations in properties as a function of particle size and also due to doping with trivalent elements (La and Nd). It was found that the lattice parameter of cerium oxide nanoparticles increases with decrease in particle size. Also Raman allowed mode shift to lower energies and the peak at 464 cm-1 becomes broader and asymmetric. The size dependent changes in cerium oxide were correlated to increase in oxygen vacancy concentration in the cerium oxide lattice. The doping of cerium oxide nanoparticles with trivalent elements introduces more oxygen vacancies and expands the cerium oxide lattice further (in addition to the lattice expansion due to the size effect). The lattice expansion is greater for La-doped cerium oxide nanoparticles compared to Nd-doping due to the larger ionic radius of La compared to Nd, the lattice expansion is directly proportional to the dopant concentration. The synthesized cerium oxide nanoparticles were used to develop an electrochemical biosensor of hydrogen peroxide (H2O2). The sensor was useful to detect H2O2 concentrations as low as 1µM in water. Also the preliminary testing of the sensor on tomato stem and leaf extracts indicated that the sensor can be used in practical applications such as plant physiological studies etc. The nanomolar concentrations of cerium oxide nanoparticles were also found to be useful in decreasing ROS (reactive oxygen species) mediated cellular damages in various in vitro cell cultures. Cerium oxide nanoparticles reduced the cellular damages to the normal breast epithelial cell line (CRL 8798) induced by X-rays and to the Keratinocyte cell line induced by UV irradiation. Cerium oxide nanoparticles were also found to be neuroprotective to adult rat spinal cord and retinal neurons. We propose that cerium oxide nanoparticles act as free radical scavenger (via redox reactions on its surface) to decrease the ROS induced cellular damages. Additionally, UV-visible spectroscopic studies indicated that cerium oxide nanoparticles possess auto-regenerative property by switching its oxidation state between Ce3+ and Ce4+. The auto-regenerative antioxidant property of these nanoparticles appears to be a key component in all the biological applications discussed in the present study.
|
110 |
Polymerisation of vinyl monomers in continuous-flow reactors. An experimental study, which includes digital computer modelling, of the homopolymerisation of styrene and methylmethacrylate by anionic and free radical mechanisms respectively in continuous flow-stirred-tank reactors.Bourikas, N. January 1976 (has links)
An introduction is given to the background theory and
scientific literature of the major subject areas of interest in
this thesis, namely the chemistry of free radical and anionic
polymerisation, molecular weight control in each type of polymerisation,
polymerisation reactors, computer simulation of
polymerisation processes and polymer characterisation by gel
permeation chromatography.
A novel computer model has been devised, based on the
analysis of the polymerisation process in terms of the reaction
extent of each reactant and the use of generation functions
to describe the concentration of living and dead polymeric
species, for the free radical, solution polymerisation of methylmethacrylate
in a CSTR. Both heat and mass balance expressions
have been described. Conversion, Mn and Mw were monitored.
To test the model a reactor was designed and constructed.
A detailed description of the reactor and the experimental
conditions used for the validation of the model are given.
The results of these studies are presented and excellent agreement
is shown between model predictions and experiments up to 30%
conversion for Mn
w and % conversion.
A similar study is described for the anionic polymerisation
of styrene in tetrahydrofuran as solvent, in a CSTR. In this
work the computer model becomes 'stiff' when realistic rate
constants are introduced in the kinetic expressions.
Experimental difficulties were encountered in obtaining
reproducible results in the anionic work. A new approach of
using 'scavengers' as protecting agents for the living chains
is described. A scavenger was successfully employed in the
preparation of block copolymers using a tubular reactor.
Block copolymerisation, in addition to providing a means of
checking the number of the 'living' chains inside the reactor,
is of interest in its own right.
All the experimental findings are discussed in relation
to the currently accepted views found in the scientific
literature.
|
Page generated in 0.0641 seconds