102 research outputs found
Administrative associations and the universities: [Address to association of Canadian university information bureaux, Atlantic Region]
No full textEffect of protein-energy malnutrition on nuclear factor kappa B activation following global ischemia
No full textOur laboratory previously found that protein-energy malnutrition (PEM) existing prior to brain ischemia impaired functional outcome measured in an open field test, and one-third of animals showed a marked increase in reactive gliosis. It was hypothesized that PEM worsened stroke outcome by increasing inflammation via increased activation of the transcription factor, nuclear factor kappa B (NFκB). Mongolian gerbils (11-12 wk old) were randomly assigned to a control diet (12.5% protein) or a protein-deficient diet (2%) for 28 days. The control group on average gained 4.9g and the PEM group lost 7.4g. PEM gerbils had significantly decreased food intake (
THE VIBRATIONAL SPECTRA OF MOLTEN SALTS BY ATR INFRARED
No full text Aided by National Science Foundation. J. K. Wilmshurst and S. Senderoff, J. Chem. Phys., 35, 1078 (1961).Author Institution: Department of Chemistry, Oklahoma State UniversityThe infrared spectra of lithium and silver nitrate in the region has been re-examined by using Fahrenfort's ATR technique with a silicon reflecting prism. An angle of incidence considerably greater than the critical, so that the absorption coefficient largely determines the spectrum, has been used. The resulting effective pathlength is in the range required for successful study of the structure of the very intense band produced by the asymmetric stretching modes of the nitrate group. The structure of this band is indicative of the nature of the environment of the nitrate ion. The observed band structure and its interpretation will be compared with that reported by $Wilmshurst.^{1}
From Women and Sport to Gender and Sport: Transnational, Transdisciplinary, and Intersectional Perspectives
No full texthttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000303571900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701HistoryHospitality, Leisure, Sport & TourismA&HCISSCI1EDITORIAL MATERIAL5,SI667-6742
Photochemical trajectory modeling studies of the North Atlantic region during August 1993
No full textA Lagrangian photochemical trajectory model has been used to assess the factors affecting O-3 production during transport of polluted air masses across the North Atlantic Ocean. Sensitivity studies have been performed along idealized trajectories, and it is found that the potential impact of North American emission sources is maximized by transport of air at high altitudes, in drier conditions and in conditions where mixing of the air with background air masses is relatively limited. Measurements taken from the NCAR King Air aircraft as part of the North Atlantic Regional Experiment (NARE) August 1993 intensive have been used to initialize forward trajectories, calculated using European Centre for Medium-Range Weather Forecasting analyzed wind fields, from eastern North America to assess O-3 production over the Atlantic during this period. The effects of dilution of a polluted air parcel with air from the upper troposphere have also been studied, and the contribution of photochemical O-3 production to the air mass composition is found to be smaller than that of dilution, particularly for long trajectories and for conditions where dilution is relatively rapid or involves air from the stratosphere. Measurements taken from the Meteorological Research Flight Hercules aircraft over the eastern Atlantic as part of the Oxidizing Capacity of the Tropospheric Atmosphere campaign have been examined in the light of these studies. A backward trajectory analysis has been performed from one of the vertical profiles taken off the coast of Portugal on August 31, 1993, to assess the origin of the different air masses intercepted. While the lower levels are characteristic of air from the European boundary layer advected over the ocean, the upper levels show strong evidence for anthropogenic influence from North American sources, with elevated levels of O-3, NOy, CO, and aerosol. Although it cannot be concluded that this air mass definitely originated from over North America, the measured concentrations are shown to be consistent with those for an air mass from this source region experiencing some mixing with air masses in the upper troposphere
Consumers and retail food employees' attitudes, knowledge, and skills with respect to soyfoods
No full textThis study sought to develop an informed understanding about consumers and
retail food employees' perceived attitudes, knowledge and skills needed regarding
soyfood purchase decisions. This exploratory research utilized a quantitative technique
(self-administered questionnaire) and a qualitative technique (interview) to obtain data
from participating grocery shoppers and retail food employees at two Saskatoon Co-op
stores, in Saskatoon, Saskatchewan, Canada. Descriptive and inferential statistics,
frequency distributions, t-test, and Pearson chi-square test were used to assess
quantitative data. A significance level of 5% was adopted. Interviews and open-ended
questions and comments from the questionnaires were categorized into major themes,
coded, and synthesized into descriptive reports.
Findings of the questionnaire indicated that the demographics of the declared
soy users at the sampled food stores were no different from grocery shoppers or
declared soy non-users, i.e., predominantly female, Caucasian, older than 45 years old,
household yearly income higher than CAD$50,000, and possessing at least a trade,
college or university certificate, or diploma. There also was no significant difference
with respect to the consumption of vegetables and fruits, nuts and beans, and dairy
products between declared soy users and declared soy non-users. The majority of
shoppers indicated that soy is healthy. When asked about soy health benefits, most
shoppers indicated that soy helped reduce the risks of heart disease; however, they were
neutral with respect to the soy's ability to help reduce the risk of cancer and bone loss,
to cause allergies, and to alter estrogen levels in the body. The percentage of soy users
who agreed with the following statements "Soy is low in cholesterol", "Soy helps reduce the risks of heart disease", "Soy is healthy", "Soy helps reduce risk of cancer",
"Soy consumption is completely safe", and "Soy can fulfill part of my protein needs"
was significantly higher when compared to soy non-users. Findings suggest that
grocery shoppers at both food stores purchased soy products mainly because these
foods were nutritious and good sources of protein. Any health claim usually associated
to soy with respect to the prevention of chronic diseases was not indicated as a major
factor that would influence the purchase of soy foods. Lack of knowledge and cooking
skills were identified by most participating grocery shoppers as major barriers to
consuming soy products. Price reduction and taste improvement were identified as
factors that would increase consumption of soy products.
The majority of grocery shoppers and food store employees indicated interest
in learning more about soy products. Learning strategies suggested by employees were
training sessions, cooking classes, taste tests, and information pamphlets.
This research identified important factors contributing to soy foods
consumption that can be used as a starting point to develop a specific framework in
which to further examine consumer knowledge and consumption behaviours relating to
other aspects of soy and other legumes
Mechanism of valproic acid induced dysmorphogenesis via oxidative stress and epigenetic regulation at the Hoxa2 gene promoter
No full textValproic acid (2-propylpentanoic acid, VPA) is a clinically used anti-epileptic drug and an
effective mood stabilizer. VPA is also a histone deacetylase inhibitor and can induce embryonic
malformations in both humans and mice. The mechanism(s) of VPA-induced teratogenicity are not
well characterized. The objectives of my study were three fold, to: (i) investigate the effect of VPA on
mouse embryonic development, (ii) characterize the putative mechanism(s) of VPA-induced
teratogenicity and, (iii) investigate VPA associated epigenetic regulation of Hoxa2 gene in cell lines
and in developing embryos. Whole mouse embryo cultures were treated with VPA at doses of 0, 50
(0.35 mM), 100 (0.70 mM), 200 (1.4 mM), and 400 µg/mL (2.8 mM), encompassing the therapeutic
range of 0.35 mM to 0.70 mM. Van Maele-Fabry’s morphologic scoring system was used to
quantitatively assess embryonic organ differentiation and development. Hoxa2 gene expression was
measured by quantitative real-time RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction). To
assess epigenetic changes on the Hoxa2 gene promoter, DNA methylation was determined by bisulfite
(BSP) sequencing and pyrosequencing. Histone “bivalent domains” H3K4me3 (histone 3 lysine 4
trimethylation) and H3K27me3 (histone 3 lysine 27 trimethylation) associated with gene activation
repression,
respectively,
analyzed
qChIP-PCR
(quantitative
chromatin
immunoprecipitation-PCR). Telomere length and telomerase activity were analyzed in mouse
embryos and in NIH3T3 cell line treated with VPA.
Results indicate significantly increased incidence of dysmorphogenesis in embryos (11.8%, 35.3%,
47.0% and 88.3%) exposed to increasing doses of VPA (0.35 mM, 0.70 mM, 1.4 mM and 2.8 mM
respectively). Van Maele-Fabry’s quantitative differentiation assessment of developing embryos
demonstrated a significantly lower score for the circulation system, central nervous system,
craniofacial development and limb development in VPA treated embryos (0.35 mM to 2.8 mM)
compared to the untreated control group. Glutathione homeostasis was altered as indicated by
decreased total glutathione content and increased GSSG/GSH ratio in all VPA treatment groups. In
addition, a dose-dependent inhibition of Hoxa2 gene expression was observed in embryos and in the
NIH3T3 cell line exposed to VPA. Pre-treatment with ascorbic acid [1000 µg/mL (5 mM)] restored
glutathione level and normalized Hoxa2 gene expression in embryos exposed to VPA. DNA
methylation status was characterized on the Hoxa2 gene promoter at the three CpG islands; CpG
island 1 (-277 to -620 bp), CpG island 2 (-919 to -1133 bp), and CpG island 3 (-1176 to -1301 bp) in
the two cells lines (NIH3T3 and EG7) and in developing embryos. CpG sites remained unmethylated
on the Hoxa2 gene promoter in the NIH3T3 cell line which expresses the Hoxa2 gene, whereas these
same CpG sites were methylated in EG7 cells that did not express Hoxa2. CpG island 1 is closest to
Hoxa2 transcription start site and its methylation status was most affected. In developing embryos,
CpG island 1 was found to be highly methylated at E6.5 when Hoxa2 is not expressed, whereas the
methylation status of CpG sites on the CpG island 1 declined between E8.5 and E10.5 when Hoxa2
expression is present. VPA induced methylation of several CpG sites on CpG island 1 in NIH3T3 cell
line and in E10.5 embryos when Hoxa2 expression was down regulated following VPA exposure. In
addition, embryos and the NIH3T3 cell line treated with VPA impacted the “bivalent domains”
resulting in increased H3K27me3 enrichment and decreased H3K4me3 enrichment on Hoxa2
promoter. Pre-treatment with ascorbic acid normalized Hoxa2 expression and histone bivalent domain
changes and prevented increased DNA methylation following VPA exposure. Moreover, the
telomerase activity and telomere length were both impacted by changes in glutathione redox potential
induced by VPA. Oxidative stress following VPA treatment reduced telomerase activity and
accelerated telomere shortening.
These results are the first to demonstrate: (i) a correlation between VPA dose and total
morphologic score in the developing mouse embryos. VPA impacted embryonic tissue differentiation
and neural system development in the dose range of 0.35 mM to 2.8 mM; (ii) VPA altered glutathione
homeostasis in cultured mouse embryos and inhibited Hoxa2 gene expression; (iii) Histone bivalent
domains of H3K27 and H3K4 trimethylation and DNA methylation status at the Hoxa2 gene
promoter region were altered following treatment with VPA. This appears to be the epigenetic event
in transcriptional silencing of Hoxa2 gene expression after VPA exposure; and (iv) Ascorbic acid
normalizes glutathione homeostasis, H3K27 and H3K4 trimethylation and DNA methylation status,
restoring Hoxa2 gene expression following VPA exposure. Taken together our results show VPA-
induced altered glutathione homeostasis, telomere shortening and telomerase dysfunction, and an
inhibition of Hoxa2 gene expression leads to developmental abnormalities. Exposure to ascorbic acid
had a protective effect on developing embryos exposed to VPA
In vitro studies using curcumin and curcumin analogues as candidate mitochondria-targeting anticancer agents affecting colon cancer cells
No full textCurcumin is one of the major curcuminoids produced by the ginger family Zingiberaceae. These curcuminoids possess pharmacological properties that include anticancer activities. We have evaluated some synthetic curcumin analogues that have shown potential as anticancer drugs. These antineoplastic agents bearing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore are electrophiles which are designed to preferentially react with sulfhydryl groups present in proteins as opposed to amino and hydroxyl groups present in DNA. In previous pilot studies, three derivatives examined in this thesis showed inhibition towards human cancer cell lines such as Molt 4/C8 and CEM T-lymphocytes. In this thesis work, I determined the cytotoxicity of these derivatives and curcumin towards human colon cancer (HCT-116) cells and also normal colon epithelial (CRL-1790) cells, and examined the possible mechanism(s) involved. I hypothesized that they act via induction of reactive oxygen species (ROS) which elicit a transient surge of mitochondrial ROS generation and a phenomenon known as ROS-induced ROS release (RIRR), along with the mitochondrial permeability transition (MPT) and mitochondrion –dependent apoptosis. I asked whether these agents react with some of the key protein thiols in the mitochondria whose oxidation/alkylation results in mitochondrion - dependent apoptosis.
NC-2109 and NC-2346 were found to be potent cytotoxic agents based on their GI50 values of 0.87 ± 0.38 μM and 0.90 ± 0.22 μM, respectively, and were more potent than the anticancer drug 5-fluorouracil (GI50 = 5.47 ± 0.55 μM) and curcumin (GI50 = 3.50 ± 0.36 μM). However NC-2109 was found to have a better selectivity towards cancer cells over normal cells (a selectivity index of 18.81 versus 5-FU, curcumin and NC-2346 which had selectivity indices of 1.87, 16.75 and 4.61, respectively).
In the investigations of the mechanisms involved, both curcumin and curcumin analogues were able to induce mitochondrial ROS production. Moreover, curcumin and its synthetic counterparts showed a biphasic ROS profile which is most characteristic of RIRR. Treatment with these agents also led to the disruption of the mitochondrial membrane potential, suggesting oxidation of protein thiols and the opening of the mitochondrial permeability transition pore which is an important step to initiate mitochondria-directed apoptosis. This possibility was confirmed based on GSSG/GSH ratios, since curcumin, NC-2346 and NC-2109 all produced a higher GSSG/GSH ratio than the controls. In addition to their ability to depolarize the mitochondrial membrane in HCT-116 cells, that these molecules acted via the mitochondrial pathway were further authenticated based on their ability to induce mitochondrial swelling in rat liver mitochondria.
In another part of this thesis I evaluated the involvement of the critical thiol protein adenine nucleotide translocase (ANT), a bifunctional protein that plays a central role in mitochondrial apoptosis. ANT has four different isoforms; ANT1 and ANT3 are proapoptotic, while ANT2 and ANT4 are antiapoptotic and are overexpressed in cancer states. A combination approach using ANT2 siRNA however did not conclusively show whether these agents acted synergistically with ANT2 knockdown to potentiate mitochondria-mediated cell death. An alternative combination approach was the use of carboxyatractyloside (CAT) which binds to and retains ANT in its ‘c’ conformation, exposing thiols and potentially driving a cell towards programmed cell death. The presence of CAT enhanced the ability of curcumin and its synthetic analogs to collapse the mitochondrial membrane potential, an important step in mitochondrial-mediated apoptosis.
In conclusion, curcumin and the curcumin analogue NC-2109 were found to be cytotoxic in vitro, towards HCT-116 cells and also showed good selectivity. In addition, these two molecules were found to be ROS inducers, and coincidentally oxidized cellular thiols and caused depolarization of the mitochondrial membrane potential. The results support a mechanism of mitochondrial-mediated cell death upon MPT pore formation (mitochondrial swelling), perhaps involving ANT2. This conclusion was further supported by the potentiation of cell death in the presence of the ANT2 inhibitor, CAT
D-lactic acid metabolism and control of acidosis
No full textD-lactic acidosis (DLA) is a disease associated with D-lactatemia, acidosis and neurological signs. However, these associations are ill-defined. Bacterial fermentation in the intestine causes increasing D-lactic acid concentrations in the body. Therefore, DLA is reported secondary to gastrointestinal diseases, such as short bowel syndrome, gastroenteritis or diarrhea. Despite intestinal origin, sudden D-lactatemia is often a result of impaired D-lactate metabolism in the body.
Aims of this work were to determine: 1) Influence of the presence of D-lactate or acidity on neurological disturbances; 2) Effectiveness of parenteral NaHCO3 therapy in correcting cerebrospinal acidity and DLA; 3) Prevalence of DLA in diarrheic lambs and fecal D-lactate thresholds; 4) Effectiveness of malate in preventing DLA.
The methodological tools consisted of animal models (calves and lambs): 1) Advanced surgical procedure in calves for long-lasting atlanto-occipital catheterizations; 2) Intravenous infusions of acids to experimentally induce acidosis; 3) Intravenous NaHCO3 therapies; 4) Sampling of cerebrospinal fluid (CSF), blood, urine and feces from experimental / treated calves or diarrheic lambs for blood gas analysis, and D-lactate separation by chromatography.
D-lactate entered the central nervous system (> 2 mmol/L) from the circulation following experimentally induced D-lactatemia (> 5 mmol/L) and was responsible for neurological disturbances which correlated (r = 0.9, P < 0.05) with both CSF and serum D-lactate concentrations. A zenith of neurological disturbances, ataxia was evident when D-lactate concentration exceeded 12 mmol/L (CSF) and 26 mmol/L (serum), however, a nadir of acidosis (pH 6.9) caused by HCl infusions produced only mild neurological disturbances (P < 0.05). Therapeutic NaHCO3 infusions did not result paradoxical CSF acidosis, but supportive in correcting (P < 0.05) acidosis (ÄpH + 0.11) and D-lactatemia in calves.
In lambs, metabolic acidosis following a range of mild to severe diarrhea was observed with a corresponding range of D-lactate concentrations in both serum (< 0.05−24.0 mmol/L) and feces (< 0.05−31.0 mmol/L). D-lactate was absorbed into the circulation when the fecal D-lactate concentration exceeded 10.2 mmol/L (threshold).
In calves, moderate oral use of malate produced a > 50% (P < 0.05) decrease in fecal and serum D-lactate concentrations suggesting prebiotic properties to prevent DLA.
This dissertation answers the critical questions about the onset of neurological signs in D-lactic acidosis, and advances the current knowledge on the metabolism of D-lactate, the prevention and treatment of acidosis
- …
