The role of aryl hydrocarbon receptor and the reactive oxygen species in the modulation of glutathione transferase by heavy metals in murine hepatoma cell lines.

Glutathione transferase (GST) is a phase II detoxifying enzyme that plays a protective mechanism against oxidizing substances and toxic contaminants. Among these contaminants, heavy metals and polycyclic and halogenated aromatic hydrocarbons (PHAHs) have been shown to exert their toxic effects through the modulation of detoxifying enzymes, including the GSTs. Recently, we showed that heavy metals particularly Hg2+, Pb2+, and Cu2+ modulate the expression of phase II detoxifying enzymes such as NAD(P)H:quinone oxidoreductase 1 and Gsta1 in a concentration- and time-dependent manner.

The impact of the mTOR inhibitor sirolimus on the proliferation and function of pancreatic islets and ductal cells.

Aims/hypothesis: The Edmonton Protocol for islet transplantation has provided hope for type 1 diabetic patients. However, this protocol requires lifelong immunosuppression, specifically sirolimus, a cellular antiproliferate. The effect of sirolimus on human pancreatic ductal cells (HDCs) is not known.

Cytochrome P450 enzymes: central players in cardiovascular health and disease.

Cardiovascular disease (CVD) is a human health crisis that remains the leading cause of death worldwide. The cytochrome P450 (CYP) class of enzymes are key metabolizers of both xenobiotics and endobiotics. Many CYP enzyme families have been identified in the heart, endothelium and smooth muscle of blood vessels.

Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells.

Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility.

Perceptions and attitudes of Canadian dentists toward digital and electronic technologies.

Objectives: To determine dentists" perceptions of the usefulness of digital technologies in improving dental practice and resolving practice issues; to determine dentists" willingness to use digital and electronic technologies; to determine perceived obstacles to the use of digital and electronic technologies in dental offices; and to determine dentists" attitudes toward Internet privacy issues.

Methods: An anonymous, self-administered survey of Canadian dentists was conducted by mail. A potential mailing list of 14,052 active Canadian dentists was compiled from the 2003 records of provincial regulatory bodies.

Correlation of skeletal maturation stages determined by cervical vertebrae and hand-wrist evaluations.

The aim of this study was to assess the correlation between the Fishman maturation prediction method (FMP) and the cervical vertebral maturation (CVM) method for skeletal maturation stage determination. Hand-wrist and lateral cephalograms from 79 subjects (52 females and 27 males) were used. Hand-wrist radiographs were analyzed using the FMP to determine skeletal maturation level (advanced, average, or delayed) and stage (relative position of the individual in the pubertal growth curve).

The treatment effects of Invisalign orthodontic aligners: a systematic review.

Background: The authors conducted a systematic review of the literature to determine the treatment effects of the Invisalign orthodontic system (Align Technology), Santa Clara, Calif.).

Types Of Studies Reviewed: The authors reviewed clinical trials that assessed Invisalign's treatment effects in nongrowing patients.

In vitro uptake of gelatin nanoparticles by murine dendritic cells and their intracellular localisation.

The long term goal of this study is to develop an efficient nanoscopic vaccine delivery system, based on the biodegradable and natural polymer gelatin, to deliver therapeutic protein antigens along with adjuvants into dendritic cells (DCs). In this study, gelatin nanoparticles were tested for qualitative and quantitative uptake in murine DCs in vitro. A second aim of this study was to prove that the carrier system is able to deliver tetramethylrhodamine conjugated dextran (TMR-dextran), as a model drug into the DCs.

Proposed reference point for 3-dimensional cephalometric analysis with cone-beam computerized tomography.

Introduction: The purpose of this article is to propose a reference landmark for use in 3-dimensional cephalometric analysis with 3-dimensional volumetric images.

Methods: Cone-beam computerized tomographies were obtained from 10 adolescent patients. They were analyzed with AMIRA software (Mercury Computer Systems, Berlin, Germany).

The role of oxidative stress in the modulation of aryl hydrocarbon receptor-regulated genes by As3+, Cd2+, and Cr6+.

Heavy metals alter the capacity of AhR ligands to induce the bioactivating phase I and the detoxifying phase II xenobiotic-metabolizing enzymes but the mechanism(s) remain unknown. In the present study, we evaluated the role of As(3+)-, Cd(2+)-, and Cr(6+)-induced oxidative stress on the expression of Cyp1a1, Nqo1, and Gst ya in Hepa 1c1c7 cells. Both Cd2+ and Cr6+, but not As3+, increased the production of ROS.

Kinematics of head movement in simulated low velocity rear-end impacts.

Objectives: To evaluate kinematics of head movement related to impact velocity, gender and awareness in simulated low velocity rear-end impacts.

Methods: Thirty individuals were subjected in random order to three rear-end impacts: two unexpected impacts causing chair acceleration of 4.5m/s2 (slow) and 10.

The role of sternocleidomastoid muscle in simulated low velocity rear-end impacts.

The objectives of this study were to evaluate behavior of sternocleidomastoid muscle (SCM) electromyogram (EMG) related to impact velocity, gender, awareness and kinematics of head movement in simulated low velocity rear-end impacts. Twenty-nine healthy adults (17 male) were subjected in random order to three rear-end impacts: Two unexpected impacts causing chair accelerations of 4.5 m/s(2) (slow) and 10.

Down-regulation of aryl hydrocarbon receptor-regulated genes by tumor necrosis factor-alpha and lipopolysaccharide in murine hepatoma Hepa 1c1c7 cells.

Although much is known concerning the effects of inflammation and oxidative stress on the cytochrome P450 1A1 (CYP1A1), little is known about the modulation of other aryl hydrocarbon receptor (AHR)-regulated genes such as glutathione-S-transferase Ya (GST Ya) and NAD(P)H:quinone oxidoreductase (QOR) by inflammation. In the present study, the effect of tumor necrosis factor (TNF)-alpha and lipopolysaccharides (LPS) on the constitutive and inducible expression of the AHR-regulated genes cyp1a1, GST Ya, and QOR was determined in murine hepatoma Hepa 1c1c7 (WT), AHR-deficient (C12), and AHR nuclear translocator protein (ARNT)-deficient (C4) cells. We found that both TNF-alpha and LPS strongly repressed the constitutive expression and the beta-naphthoflavone-mediated induction of cyp1a1, GST Ya, and QOR in WT but not in C12 and C4 cells.

Benzo[a]pyrene, 3-methylcholanthrene and beta-naphthoflavone induce oxidative stress in hepatoma hepa 1c1c7 Cells by an AHR-dependent pathway.

Polycyclic aromatic hydrocarbons have been shown to cause oxidative stress in vitro and in vivo in various animal models but the mechanisms by which these compounds produce oxidative stress are unknown. In the current study we have investigated the role of the aryl hydrocarbon receptor (AHR) in the production of reactive oxygen species (ROS) by its cognate ligands and the consequent effect on cyp1a1 activity, mRNA and protein expressions. For this purpose, Hepa 1c1c7 cells wild-type (WT) and C12 mutant cells, which are AHR-deficient, were incubated with increasing concentrations of the AHR-ligands, benzo[a]pyrene (B[a]P, 0.

tert-Butylhydroquinone is a novel aryl hydrocarbon receptor ligand.

In contrast to the beneficial effects of tert-butylhydroquinone (tBHQ) as a food antioxidant, a number of studies have shown that chronic exposure to tBHQ may induce carcinogenicity. Therefore, we examined the ability of tBHQ to induce the cytochrome P450 1a1 (Cyp1a1), an enzyme known to play an important role in the chemical activation of xenobiotics to carcinogenic derivatives. A significant concentration-dependent increase in Cyp1a1 mRNA, protein, and activity occurred after treatment of murine hepatoma Hepa 1c1c7 cells with tBHQ.

The Klippel-Feil syndrome: a case report.

Short neck and fusion of cervical vertebrae are observed in several genetic conditions and well-defined syndromes. An 8-year-old boy with a short neck, low-set posterior hairline, deafness and limited neck motion was suspected of having such a condition. Clinical and radiographic examination led to the diagnosis of Klippel-Feil syndrome.

Mechanisms and models of peripheral CD4 T cell self-tolerance.

Each response made by our immune system is either to promote or to prevent immune reactivity. That the immune system can successfully achieve both goals under specific biological conditions depends on central and peripheral tolerance mechanisms. Over the years, various experimental systems have been generated to study peripheral CD4 T cell tolerance.

Modulation of aryl hydrocarbon receptor-regulated gene expression by arsenite, cadmium, and chromium.

Aryl hydrocarbon receptor (AhR) ligands and heavy metals are environmental co-contaminants and their molecular interaction may disrupt the coordinated regulation of AhR-dependent phase I and II drug metabolizing enzymes. To determine the effect of heavy metals on the AhR-regulated genes: cytochrome P4501A1 (Cyp1a1), NAD(P)H: quinone oxidoreductase (QOR) and glutathione S-transferase Ya (GST Ya), murine hepatoma Hepa 1c1c7 cells were treated with increasing concentrations of As3+ (1-10 microM), Cd2+ (1-25 microM) and Cr6+ (1-25 microM) with or without the AhR ligands: 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.1 nM), 3-methylcholanthrene (0.

Improved islet survival and in vitro function using solubilized small intestinal submucosa.

In vitro proliferation of isolated pancreatic islets has become an area of great interest given the scarcity of clinical islet donors and the islet mass requirements for clinical islet transplantation. Small intestinal submucosa (SIS), a naturally occurring extracellular matrix, has been investigated to promote wound healing, tissue remodeling and cell growth. This study evaluated recovery and function of isolated canine pancreatic islets following in vitro tissue culture.

Characterization of poly(D,L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells.

Biodegradable nanoparticles made of poly(D,L-lactic acid-co-glycolic acid) (PLGA) copolymer were characterized for enhanced delivery of antigens to murine bone marrow derived dendritic cells (DCs) in vitro. PLGA nanoparticles were efficiently phagocytosed by the DCs (CD11c+, MHC class II+, CD86+) in culture, resulting in their intracellular localization. The efficiency of the uptake was influenced by the incubation time and nanoparticle concentration.

Endogenous pancreatic enzyme activity levels show no significant effect on human islet isolation yield.

Despite advances in human islet isolation, islet yield remains inconsistent and unreliable. In recent studies, it has been suggested that serine proteases, in particular trypsin, have been shown to have a damaging effect on islet yield. This study evaluated enzyme activity levels throughout 42 human islet isolation procedures.

Endogenous Pancreatic Enzyme Activity Levels Show no Significant Effect on Human Islet Isolation Yield.

Despite advances in human islet isolation, islet yield remains inconsistent and unreliable. In recent studies, it has been suggested that serine proteases, in particular trypsin, have been shown to have a damaging effect on islet yield. This study evaluated enzyme activity levels throughout 42 human islet isolation procedures.

Improvement of pancreatic islet isolation outcomes using glutamine perfusion during isolation procedure.

During procurement, isolation, and transplantation, islets are exposed to high levels of oxidative stress triggering a variety of signaling pathways that can ultimately lead to cell death. Glutamine is an important cellular fuel and an essential precursor for the antioxidant glutathione. The aim of this study was to examine the role of intraductal glutamine administration in facilitating recovery of isolated rat islets from pancreases subjected to a clinically relevant period of warm ischemia.

Improvement of Pancreatic Islet Isolation Outcomes Using Glutamine Perfusion during Isolation Procedure.

During procurement, isolation, and transplantation, islets are exposed to high levels of oxidative stress triggering a variety of signaling pathways that can ultimately lead to cell death. Glutamine is an important cellular fuel and an essential precursor for the antioxidant glutathione. The aim of this study was to examine the role of intraductal glutamine administration in facilitating recovery of isolated rat islets from pancreases subjected to a clinically relevant period of warm ischemia.