Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells

Increased dopamine catabolism may be associated with oxidative stress and neuronal cell death in Parkinson's disease. The present study was carried out to examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1 and HO-2) in human neuroblastomas (SK-N-SH cell line) and the effects of selegiline and antioxidants on this expression. Cells were kept with close control of pH and were incubated with varying concentrations of dopamine (0.1-100 µM) for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse transcription-polymerase chain reaction amplification. The mRNA expression of HO-1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA increased after dopamine treatment, in a dose-dependent manner, in all cell lines studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2 protein expression was analyzed by Western blotting. HO-1 protein was undetectable in untreated SK-N-SH cells and increased after treatment with dopamine. In contrast, the HO-2 protein (36 kDa) was detected in untreated cells and the levels did not change as a result of treatment. alpha-Tocopherol (10-100 µM) and ascorbic acid (100 µM) did not attenuate the effects of dopamine. Selegiline (10 µM) produced significant increase (P < 0.01) in the induction of HO-1 by dopamine (more than six times the control values). The increased expression of HO-1 following dopamine treatment indicates that dopamine produces oxidative stress in this cell line.

Pim-1 kinase inhibits the activation of reporter gene expression in Elk-1 and c-Fos reporting systems but not the endogenous gene expression: an artifact of the reporter gene assay by transient co-transfection

We have studied the molecular mechanism and signal transduction of pim-1, an oncogene encoding a serine-threonine kinase. This is a true oncogene which prolongs survival and inhibits apoptosis of hematopoietic cells. In order to determine whether the effects of Pim-1 occur by regulation of the mitogen-activated protein kinase pathway, we used a transcriptional reporter assay by transient co-transfection as a screening method. In this study, we found that Pim-1 inhibited the Elk-1 and NFkappaB transcriptional activities induced by activation of the mitogen-activated protein kinase cascade in reporter gene assays. However, Western blots showed that the induction of Elk-1-regulated expression of endogenous c-Fos was not affected by Pim-1. The phosphorylation and activation of neither Erk1/2 nor Elk-1 was influenced by Pim-1. Also, in the gel shift assay, the pattern of endogenous NFkappaB binding to its probe was not changed in any manner by Pim-1. These data indicate that Pim-1 does not regulate the activation of Erk1/2, Elk-1 or NFkappaB. These contrasting results suggest a pitfall of the transient co-transfection reporter assay in analyzing the regulation of transcription factors outside of the chromosome context. It ensures that results from reporter gene expression assay should be verified by study of endogenous gene expression.

Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition

The present study investigated the effect of silibinin, the principal potential anti-inflammatory flavonoid contained in silymarin, a mixture of flavonolignans extracted from Silybum marianum seeds, on palmitate-induced insulin resistance in C2C12 myotubes and its potential molecular mechanisms. Silibinin prevented the decrease of insulin-stimulated 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) uptake and the downregulation of glutamate transporter type 4 (GLUT4) translocation in C2C12 myotubes induced by palmitate. Meanwhile, silibinin suppressed the palmitate-induced decrease of insulin-stimulated Akt Ser473 phosphorylation, which was reversed by wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K). We also found that palmitate downregulated insulin-stimulated Tyr632 phosphorylation of insulin receptor substrate 1 (IRS-1) and up-regulated IRS-1 Ser307 phosphorylation. These effects were rebalanced by silibinin. Considering several serine/threonine kinases reported to phosphorylate IRS-1 at Ser307, treatment with silibinin downregulated the phosphorylation of both c-Jun N-terminal kinase (JNK) and nuclear factor-κB kinase β (IKKβ), which was increased by palmitate in C2C12 myotubes mediating inflammatory status, whereas the phosphorylation of PKC-θ was not significantly modulated by silibinin. Collectively, the results indicated that silibinin prevented inhibition of the IRS-1/PI3K/Akt pathway, thus ameliorating palmitate-induced insulin resistance in C2C12 myotubes.

Sphingosine-1-phosphate-evoked invasion of follicular thyroid cancer cells : evidence for the involvement of HIF-Iα, MMP2 and MMP9

Sphingolipids are widely expressed molecules, which traditionally were considered to have majorly structural properties. Nowadays, however, they are implicated in a wide range of different biological processes. The bioactive lipid sphingosine 1-phosphate (S1P) has emerged during the past decade as one of the most studied molecules due to its proliferative and pro-migratory abilities both during normal physiology and in the pathology of a subset of different diseases. Migration and invasion of cancer cells require changes in cell behavior and modulation of the tissue microenvironment. Tumor aggressiveness is markedly enhanced by hypoxia, in which hypoxia inducible transcription factors 1-2α (HIF-1-2α) are activated to promote metabolism, proliferation and migration. Invasion requires degradation of the extracellular matrix (ECM) achieved by several degrading and remodeling enzymes. Matrix metalloproteinases (MMPs) are broadly expressed and well accepted as proteolytic enzymes with essential roles both in normal physiology and in pathology. Previously, S1P was shown to strongly evoke migration of follicular ML-1 thyroid cancer cells. The objective of this study was to further investigate and understand the mechanisms behind this regulation. In the first project it was demonstrated that S1P enhances the expression and activity of HIF-1α. S1P enhanced the expression of HIF-1α by increasing its synthesis and stability. The S1P-increased HIF-1α was mediated via S1P3, Gi/0, PI3K, PKCβI, ERK1/2, mTOR and translation factors p70S6K and eIF4E. Finally, it was shown that HIF-1α mediated S1P-induced migration. The ECM is constituted of a complex and coordinated assembly of many types of proteins. In order to be able to invade, cells need to break down the ECM, therefore several key players in this event were investigated in the second project. S1P increased the secretion and activity of MMP2 and MMP9 via S1P-receptor 1 and 3 and that these MMPs participated in the S1P-facilitated invasion of ML-1 cells. In this interplay, calpains and Rac1 were involved, both of which are crucial players in migration and invasion. The prognosis for some types of thyroid cancer is relatively good. However, there are forms of thyroid cancers, for which there are no treatments or the current available treatments are inefficient. Thus, new medical interventions are urgently needed. In the third project the significance of the S1P-receptor modulating drug FTY720, which is currently used for the treatment of multiple sclerosis (MS), was studied. The effect of FTY720 was tested on several thyroid cancer cell lines, and it inhibited the proliferation and invasion of all cancer cell lines tested. In ML-1 cells, FTY720 attenuated invasion by blocking signaling intermediates important for migration and invasion of the cells. Moreover, FTY720 inhibited the proliferation of ML-1 cells by increasing the expression of p21 and p27, hence, inducing cell arrest in G1 phase of the cell cycle. Thus, it can be suggested that FTY720 could be used in the treatment of thyroid cancer.

The effect of a diet education with six iso-caloric meals on the body weight and blood glucose of diabetes type 2 patients

The treatment of Diabetes should not only be sought through drug administration; diet is also a part of its treatment. The aim of this study was to determine the effect of a diet with six meals having equal calories on the body weight and blood glucose on diabetes type 2 patients. This research is an Experimental study conducted in 2009 on 181 patients with diabetes. The patients visited the IDSF (Iranian Diabetes Society of Fars) weekly and the patients to be studied were randomly divided into two groups of 85 and 96 patients, respectively. The participants were repeatedly requested to consume their calculated calorie in six equal parts. The average age in the Experimental and Control groups were 51.2 ± 13.3 and 53.1 ± 9.4, respectively. The mean body weight and fasting blood glucose at the beginning of the study in Experimental and Control groups were 66.3 ± 9.4 and 69.1 ± 11.1 kg, 198.9 ± 35.1, and 199.8 ± 39.1 mg.dL-1, respectively. At the end of the study, however, the values were 63.5 ± 7.5 and 66.98 ± 9 kg, 139.5 ± 34.6 and 164.2 ± 22.1 mg.dL-1, respectively. Only the mean fasting blood glucose at the end of the study revealed a significant difference (p-value = 0.001). The results show that educating those afflicted with Diabetes Type 2 aiming at changing their diet can greatly help them manage their blood glucose.

Estimate of dietary intake of chloropropanols (3-MCPD and 1,3-DCP) and health risk assessment

Chloropropanols, including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3-dichloropropan-2-ol (1,3-DCP), comprise a group of chemical contaminants with carcinogenic and genotoxic properties. They have been found in a variety of processed foods and food ingredients, such as hydrolyzed vegetable protein, soy sauce, cereal-based products, malt-derived ingredients, and smoked foods. This study aimed to assess the dietary exposure to 3-MCPD and 1,3-DCP in Brazil and verify whether the presence of these substances in foods could represent health risks. The intake was calculated by combining data on food consumption, provided by the Consumer Expenditure Survey 2008-2009, with the levels of contaminant occurrence determined by gas chromatography-mass spectrometry. The exposure to 3-MCPD ranged from 0.06 to 0.51 µg.kg bw-1.day-1 considering average and high consumers, while the intake of 1,3-DCP was estimated to be 0.0036 µg.kg bw-1.day-1 in the worst case scenario evaluated. Based on these results, it was verified that the Brazilians' exposure to chloropropanols does not present a significant health risk. However, the consumption of specific foods containing high levels of 3-MCPD could exceed the provisional maximum tolerable daily intake of 2 µg.kg bw-1 established for this compound and, therefore, represent a potential concern.

An educator's perspective of Dr. Feingold's K-P (Kaiser- Permanents) elimination diet for hyperkinetic children and others

Do evaluation of the literature and a regional observational report support Dr. Feingold's claim that the K-P (Kaiser-Permanente) elimination diet improves the behaviours of hyperkinetic children, and others? Dr. Feingold suggests that some hyperkinetic children, and other children as well, are genetically predisposed to intolerance of food additives, particularly food colours and flavours. He claims that the K-P diet, that eliminates salicylates and artificial food colours and flavours, improves the hyperkinetic child's behaviour, muscle co-ordination, and scholastic performance. Public acceptance of the K-P diet has outstripped acceptance in the medical and scientific communities. Evaluation of available data and additional studies are needed to arrive at a conclusion of acceptance or rejection of the K-P diet for hyperkinetic children and others. My interest in the K-P elimination diet for hyperkinetic children is educational. My experience as an elementary school teacher in special education and in the classroom from K-8 has taught me that attentiveness is crucial to learning. Hyperkinesis appears to impair a child's ability to attend. Learning problems appear, followed by behavioural and social problems. l If we accept the possibility of a relationship between diet and attentiveness, and attentiveness and school behaviours, then the diet-behaviour link could be of lay importance. For instance, if a diet such as the K-P diet could do what is claimed, substantial benefits could accrue to the child. One could, for example, improve a child's behaviours. One could identify attending disturbances early in the child's education, possibly minimizing, or eliminating future difficulties in school. Finally, the greatest benefit may be the fulfillment of the basic goal of our Ontario schools, that the eh~ld-,lIla1p.evelop happily and competently within our educational framework. 2 This thesis reports evidence from the literature and from a regional observational investigation to determine the possibility of a link between the behaviours of children and Dr. Feingold's K-P elimination diet. The literature research examines (1) Dr. Feingold's concept of H-LD, (2) his K-P elimination diet, and (3) the response from three sectors, medicine, science, and the public. The regional investigation examines the observed behaviours of nine children in Regional Niagara during a nine-month period on the K-P diet.

Gideon Sundback fonds, 1942, 1952, 1985-1986, 1991, 2004, n.d.

Gideon Sundback was born in Stockholm, Sweden in 1880. He was educated as an engineer and settled in the United States in 1905. While working for the Universal Fastener Company, New Jersey in 1913 he developed and patented a “separable fastener”, which improved on an earlier version of what today is known as the zipper. He later moved his family to Meadville, Pennsylvania and sought a Canadian location for the production of his new invention. He settled on St. Catharines as it was an easy commute from his Pennsylvania home and opened The Lightning Fastener Company on Niagara Street. Sundback died on June 21, 1954 and is interred in Meadville, Pennsylvania. The plant continued to operate, but with increased foreign competition the manufacture of the zipper declined. The plant closed in 1981. Source: The St. Catharines Standard, July 3, 2004 Harold Fox was a noted lawyer, academic, businessman, author and a leading authority on intellectual property. He was engaged by Gideon Sunback and the Lightening Fastening Company to combat patent infringements by Colonial Fastener in the 1930s. The relationship continued when Fox was asked to become the managing director of the company, which he did until 1949. Fox lived in St. Catharines at his home “Foxcroft” until his death in 1969. Source: http://thefoxfund.com/harold.htm (November 2, 2009)

Second Welland Canal - Book 1, Survey Map 6 - Through Grantham and Louth Townships

Survey map of the Second Welland Canal created by the Welland Canal Company showing the area between the Townships of Grantham and Louth. Identified structures associated with the Canal include the floating tow path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Features of the First Welland Canal are noted in red ink and include the old towing path, and the original bed of the Twelve Mile Creek. Local area landmarks are also identified and include streets and roads (ex. New Road, 1st Concession Road, and an unnamed road in the top right corner), an unnamed bridge along New Road, J. Martindale's House, an Old Saw Mill, Richardsons Creek, Georges Point, and an oak tree at Georges Point. Properties and property owners of note are: Concession 2 Lot 23 and Concession 3 Lot 23 in the Grantham Township, Concession 2 Lots 1 and 2, and Concession 3 Lots 1 and 2 in the Louth Township, Peter Weaver, J. Martindale, and John Bonner. A property belonging to the Board of Works is outlined in red at Georges Point.

Niagara River and Falls from Lake Erie to Lake Ontario : a series of one hundred and fifty-three original etchings (1886) Vol.2

A portfolio of 50 folio and 103 vignette etchings, printed on fine china paper, which has been pressed into a sturdy hand-made paper. The plates were printed by J.H. Daniels of Boston in black, brown, sepia or blue ink. All prints are dated, numbered, and signed or initialed in the plate by Sangster, and the folio prints have pencil signatures. Vol. 1. Vignettes (nos. 1-53) -- vol. 2. Vignettes (nos. 54-103) -- vol. 3. Plates (vol. 1 and 2, nos. 1-50).

Woodruff Family fonds, 1784 – 1983, (non-inclusive)

The Woodruff Family Collection: From the time the Woodruff Family came to Canada from the United States in 1795, they took an active role in the forming of their communities both in a civic and social manner. This is evident through the documents contained in this collection. The Woodruffs played an active role in the battles fought in Upper Canada and they were an integral part of the Village of St. Davids. They were educated, business-minded and socially engaged. They accumulated much of their fortune through land dealings. Much of this collection focuses on Samuel DeVeaux Woodruff who was principally a businessman. His dedication to his work is shown through his numerous undertakings. He made his mark on the Niagara Peninsula through his work on the railways, roads, marsh land revisions, canals and the paper industry. He was also involved with the founding of the Long Point Company and he took control of building DeVeaux Hall down to the last detail. His offspring inherited his work ethic and his business acumen. The people who married into the Woodruff Family also possessed key social, political and business ties. Anne and Margaret Clement were from a staunch Loyalist background. Samuel Zimmerman was instrumental to the founding of Niagara Falls and Judge Samuel DeVeaux left behind a legacy for poor and homeless boys in Niagara Falls, New York. The Woodruff Family undoubtedly left a mark on the Niagara Peninsula. This collection brings to light many endeavours of the family and their varied contributions.