Medical Toxicology Commons^™

Evaluation Of Reproductive And Developmental Risks Of Caffeine, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract provided.

The Professonal Responsibility Model Of Obstetrical Ethics: Avoiding The Perils Of Clashing Rights, Robert L. Brent, Frank A. Chervenak, Md, Laurence B. Mccullough, Phd

The Selected Works of Robert Brent

Obstetric ethics is sometimes represented by polarized views. One extreme asserts the rights of the fetus as the overwhelming ethical consideration. Both assertions are overly simplistic. Such oversimplification is called reductionism. This article explains the fallacy of rights-based reductionism and 2 models of obstetric ethics based on it and explains why the fetal rights reductionism model and the pregnant woman's rights reductionism model result in conceptual and clinical failure and therefore should be abandoned. The article argues for the professional responsibility model of obstetric ethics, which emphasizes the importance of medical science and compassionate clinical care of both the pregnant …

Androgen Increases Angiotensin Receptor Type 1a On Smooth Muscle Cells To Promote Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Xuan Zhang

University of Kentucky Doctoral Dissertations

The purpose of this study was to determine whether androgen promotes AT1aR expression on smooth muscle to confer high prevalence of AngII-induced AAAs in hyperlipidemic mice. In addition, we also investigate the role of androgen in the progression of established AngII-induced AAAs.

First, we sought to examine the role of endogenous androgen in the growth of established AngII-induced AAAs. By castrating male mice, we demonstrated that removal of endogenous androgen significantly decreased the progressive lumen dilation of established AngII-induced AAAs in male ApoE-/- mice, but had no effect on external AAA diameters. These results suggest that androgen contributes to the …

An Evidence-Based Review Of Fat Modifying Supplemental Weight Loss Products., Amy M Egras, William R Hamilton, Thomas L Lenz, Michael S Monaghan

College of Pharmacy Faculty Papers

Objective. To review the literature on fat modifying dietary supplements commonly used for weight loss. Methods. Recently published randomized, placebo-controlled trials were identified in PubMed, MEDLINE, International Pharmaceutical Abstracts, Cochrane Database, and Google Scholar using the search terms dietary supplement, herbal, weight loss, obesity, and individual supplement names. Discussion. Data for conjugated linoleic acid (CLA), Garcinia cambogia, chitosan, pyruvate, Irvingia gabonensis, and chia seed for weight loss were identified. CLA, chitosan, pyruvate, and Irvingia gabonensis appeared to be effective in weight loss via fat modifying mechanisms. However, the data on the use of these products is limited. Conclusion. Many obese …

Identification Of Activities Involved In Cag/Ctg Repeat Instability, Nelson Lap Shun Chan

University of Kentucky Doctoral Dissertations

CAG/CTG repeat instability is associated with at least 14 neurological disorders, including Huntington’s disease and Myotonic dystrophy type 1. In vitro and in vivo studies have showed that CAG/CTG repeats form a stable hairpin that is believed to be the intermediate for repeat expansion and contraction.

Addition of extra DNA is essential for repeat expansion, so DNA synthesis is one of the keys for repeat expansion. In vivo studies reveal that 3’ CTG slippage with subsequent hairpin formation (henceforth called the 3’ CTG slippage hairpin) occurs during DNA synthesis. It is proposed that hairpin tolerance machinery is activated because prolonged …

Mir-17* Suppresses Tumorigenicity Of Prostate Cancer By Inhibiting Mitochondrial Antioxidant Enzymes, Yong Xu, Fang Fang, Jiayou Zhang, Sajni Josson, William H. St. Clair, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Aberrant micro RNA (miRNA) expression has been implicated in the pathogenesis of cancer. Recent studies have shown that the miR-17-92 cluster is overexpressed in many types of cancer. The oncogenic function of mature miRNAs encoded by the miR-17-92 cluster has been identified from the 5' arm of six precursors. However, the function of the miRNAs produced from the 3' arm of these precursors remains unknown. The present study demonstrates that miR-17* is able to suppress critical primary mitochondrial antioxidant enzymes, such as manganese superoxide dismutase (MnSOD), glutathione peroxidase-2 (GPX2) and thioredoxin reductase-2 (TrxR2). Transfection of miR-17* into prostate cancer PC-3 …

Mycotoxins In Grains – Causes, Prevention And Control, Hester F. Vismer

INTSORMIL Presentations

Discusses mycotoxins, their effect on grain, mitigation considerations, and resulting human toxicology.

The Catalytic Function Of The Rev1 Dcmp Transferase Is Required In A Lesion-Specific Manner For Translesion Synthesis And Base Damage-Induced Mutagenesis, Ying Zhou, Jillian Wang, Yanbin Zhang, Zhigang Wang

Toxicology and Cancer Biology Faculty Publications

The Rev1-Polζ pathway is believed to be the major mechanism of translesion DNA synthesis and base damage-induced mutagenesis in eukaryotes. While it is widely believed that Rev1 plays a non-catalytic function in translesion synthesis, the role of its dCMP transferase activity remains uncertain. To determine the relevance of its catalytic function in translesion synthesis, we separated the Rev1 dCMP transferase activity from its non-catalytic function in yeast. This was achieved by mutating two conserved amino acid residues in the catalytic domain of Rev1, i.e. D467A/E468A, where its catalytic function was abolished but its non-catalytic function remained intact. In this mutant …

Troglitazone Stimulates Beta-Arrestin-Dependent Cardiomyocyte Contractility Via The Angiotensin Ii Type 1a Receptor., Douglas G G. Tilley, Anny D. Nguyen, Howard A. Rockman

College of Pharmacy Faculty Papers

Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPAR gamma-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPAR gamma activity, thus we hypothesized that a PPAR gamma agonist may exert physiologic effects via the angiotensin II type 1(A) receptor (AT1(A)R). In AT1(A)R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPAR gamma agonist troglitazone (Trog) enhanced AT1(A)R internalization and recruitment of endogenous beta-arrestin 1/2 (beta arr1/2) to the AT1(A)R. A fluorescence assay to …

Acetylation Of Wrn Protein Regulates Its Stability By Inhibiting Ubiquitination, Kai Li, Rui Wang, Enerlyn Lozada, Wei Fan, David K. Orren, Jianyuan Luo

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: WRN is a multi-functional protein involving DNA replication, recombination and repair. WRN acetylation has been demonstrated playing an important role in response to DNA damage. We previously found that WRN acetylation can regulate its enzymatic activities and nuclear distribution.

METHODOLOGY/PRINCIPAL FINDING: Here, we investigated the factors involved in WRN acetylation and found that CBP and p300 are the only major acetyltransferases for WRN acetylation. We further identified 6 lysine residues in WRN that are subject to acetylation. Interestingly, WRN acetylation can increase its protein stability. SIRT1-mediated deacetylation of WRN reverses this effect. CBP dramatically increases the half-life of wild …

Antidepressant Stimulation Of Cdp-Diacylglycerol Synthesis Does Not Require Monoamine Reuptake Inhibition, Marwa A. Aboukhatwa, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

Background: Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of …

A Bland–Altman Comparison Of The Lead Care® System And Inductively Coupled Plasma Mass Spectrometry For Detecting Low-Level Lead In Child Whole Blood Samples, Christina Sobin, Tanner Schaub, Natali Parisi, Eva De La Riva

Selected Works Temporary Series

Chronic childhood lead exposure, yielding blood lead levels consistently below 10 μg/dL, remains a major public health concern. Low neurotoxic effect thresholds have not yet been established. Progress requires accurate, efficient, and cost-effective methods for testing large numbers of children. The LeadCare® System (LCS) may provide one ready option. The comparability of this system to the “gold standard” method of inductively coupled plasma mass spectrometry (ICP-MS) for the purpose of detecting blood lead levels below 10 μg/dL has not yet been examined. Paired blood samples from 177 children ages 5.2–12.8 years were tested with LCS and ICP-MS. Triplicate repeat tests …

Letter To The Editor: Reproductive Toxicology, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

What Are The Reproductive And Developmental Risks Of Ionizing Radiation?, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

The Radiosensitization Effect Of Parthenolide In Prostate Cancer: Implications For Selective Cancer Killing By Modulation Of Intracellular Redox State, Yulan Sun

University of Kentucky Doctoral Dissertations

Parthenolide (PN), a major active component of the traditional herbal medicine feverfew, has been shown to have anti-inflammatory and anti-tumor properties. More remarkably, the cytotoxicity of PN seems selective to tumor cells but not their normal cell counterparts. In the present study, we investigate whether and how PN selectively enhances tumor sensitivity to radiation therapy by using prostate cancer cells LNCaP, DU145 and PC3, as well as normal prostate epithelial cells PrEC.

Our study demonstrates that inhibition of NF-κB pathway and suppression of its downstream target MnSOD are common mechanisms for the radiosensitization effect of PN in prostate cancer cells. …

Biochemical Characterization Of Human Mismatch Recognition Proteins Mutsα And Mutsβ, Lei Tian

University of Kentucky Doctoral Dissertations

The integrity of an organism's genome depends on the fidelity of DNA replication and the efficiency of DNA repair. The DNA mismatch repair (MMR) system, which is highly conserved from prokaryotes to eukaryotes, plays an important role in maintaining genome stability by correcting base-base mismatches and insertion/deletion (ID) mispairs generated during DNA replication and other DNA transactions. Mismatch recognition is a critical step in MMR. Two mismatch recognition proteins, MutSα (MSH2-MSH6 heterodimer) and MutSβ (MSH2-MSH3 heterodimer), have been identified in eukaryotic cells. MutSα and MutSβ have partially overlapping functions, with MutSα recognizing primarily base-base mismatches and 1-2 nt ID mispairs …

In Remembrance Of Denis Alan Trevor New, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Ionizing Radiation, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Structural Instability Of Human Ribosomal Rna Gene Clusters, Dawn Michelle Stults

University of Kentucky Doctoral Dissertations

The human ribosomal RNA genes are critically important for cell metabolism and viability. They code for the catalytic RNAs which, encased in a housing of more than 80 ribosomal proteins, link together amino acids by peptide bonds to generate all cellular proteins. Because the RNAs are not repeatedly translated, as is the case with messenger RNAs, multiple copies are required. The genes which code for the human ribosomal RNAs (rRNAs) are arranged as clusters of tandemly repeated sequences. Three of four catalytic RNAs are spliced from a single transcript. The genes are located on the short arms of the five …

Function Of Androgen Receptor In Prostate Cancer Epithelial Mesenchymal Transition And Microtubule Targeting, Menglei Zhu

University of Kentucky Doctoral Dissertations

Prostate cancer is the most frequently diagnosed non-skin cancer and the third leading cause of cancer mortality among men in the US. Androgens are functionally required for the normal growth of the prostate gland and play a critical role in prostate tumor development and progression. Epithelial-mesenchymal-transition (EMT) is an important process during normal development, and cancer cell metastasis.

This study examined the ability of androgens to influence EMT of prostate cancer epithelial cells and evaluate the effect of taxol chemotherapy on androgen signaling in prostate cancer cells in prostate cancer. The EMT pattern was evaluated on the basis of expression …