Efficacy and Long-Term Adverse Effect Pattern of Lovastatin
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Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C
Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C. OH, LTC, MC, USA, and THOMAS R. HUSTEAD, LTC, MC, USA Tripler Army Medical Center Family Medicine Residency Program, Honolulu, Hawaii Mild elevations in levels of the liver enzymes alanine transaminase and aspartate transaminase are commonly dis- covered in asymptomatic patients in primary care. Evidence to guide the diagnostic workup is limited. If the history and physical examination do not suggest a cause, a stepwise evaluation should be initiated based on the prevalence of diseases that cause mild elevations in transaminase levels. The most common cause is nonalcoholic fatty liver disease, which can affect up to 30 percent of the population. Other common causes include alcoholic liver disease, medication- associated liver injury, viral hepatitis (hepatitis B and C), and hemochromatosis. Less common causes include α1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic conditions (e.g., thyroid disorders, celiac disease, hemolysis, muscle disorders) can also cause elevated liver transaminase levels. Initial testing should include a fasting lipid profile; measurement of glucose, serum iron, and ferritin; total iron-binding capacity; and hepa- titis B surface antigen and hepatitis C virus antibody testing. If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate. Additional testing may include ultrasonog- raphy; measurement of α1-antitrypsin and ceruloplasmin; serum protein electrophoresis; and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing. Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more. -
Triggering of Erythrocyte Death by Triparanol
Toxins 2015, 7, 3359-3371; doi:10.3390/toxins7083359 OPEN ACCESS toxins ISSN 2072-6651 www.mdpi.com/journal/toxins Article Triggering of Erythrocyte Death by Triparanol Arbace Officioso 1,2, Caterina Manna 2, Kousi Alzoubi 1 and Florian Lang 1,* 1 Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, Germany; E-Mails: [email protected] (A.O.); [email protected] (K.A.) 2 Department of Biochemistry, Biophysics and General Pathology, School of Medicine and Surgery, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49-7071-29-72194; Fax: +49-7071-29-5618. Academic Editor: Azzam Maghazachi Received: 22 July 2015 / Accepted: 12 August 2015 / Published: 24 August 2015 Abstract: The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress which may activate erythrocytic Ca2+ permeable unselective cation 2+ 2+ 2+ channels with subsequent Ca entry and increase of cytosolic Ca activity ([Ca ]i). The present study explored whether and how Triparanol induces eryptosis. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell 2+ volume from forward scatter, hemolysis from hemoglobin release, [Ca ]i from Fluo3-fluorescence, and ROS formation from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. -
Inhibition of Cholesterol Biosynthesis in Hypercholesterolemia
J Med Biochem 2013; 32 (1) DOI: 10.2478/v10011-012-0020-3 UDK 577.1 : 61 ISSN 1452-8258 J Med Biochem 32: 16–19, 2013 Review article Pregledni ~lanak INHIBITION OF CHOLESTEROL BIOSYNTHESIS IN HYPERCHOLESTEROLEMIA – IS IT THE RIGHT CHOICE? INHIBICIJA BIOSINTEZE HOLESTEROLA U HIPERHOLESTEROLEMIJI – DA LI JE PRAVI IZBOR? Abdurrahman Coskun, Mustafa Serteser, Ibrahim Unsal Acibadem University, School of Medicine, Department of Biochemistry, Istanbul, Turkey Summary: Cholesterol biosynthesis is a complex pathway Kratak sadr`aj: Biosinteza holesterola je kompleksan me - comprising more than 20 biochemical reactions. Although ta boli~ki put koji obuhvata vi{e od 20 biohemijskih reakcija. the final product created in the pathway is cholesterol, the Iako je kona~an proizvod koji nastaje holesterol, interme- intermediate products, such as ubiquinone and dolichol, also dijerni proizvodi, kao {to su ubihinon i dolihol, tako|e obez- provide vital metabolic functions. Statins are HGM-CoA be |u ju vitalne metaboli~ke funkcije. Statini su inhibitori reductase inhibitors that stop the production of cholesterol HMG-KoA reduktaze koji zaustavljaju produkciju holestero- by directly inhibiting the mevalonate production. Mevalonate la di rektnom inhibicijom produkcije mevalonata. Mevalonat is a precursor of two additional vital molecules, squalene and je prekursor dva dodatna vitalna molekula, skvalena i ubihi - ubiquinone (coenzyme Q10). We hypothesized that inhibit- no na (koenzim Q10). Postavili smo hipotezu da produ`eno ing the cholesterol biosynthesis with statins for an extended trajanje inhibicije biosinteze holesterola statinima mo`e da duration may potentiate the oxidative stress, neurodegener- po tencira oksidativni stres, neurodegenerativne bolesti i ative disease and cancer. Our recommendation was to meas- kan cer. -
Gamma Glutamyl Transferase (GGT) NCD 190.32
Medicare National Coverage Determination (NCD) Policy TRANSFERASE GAMMA GLUTAMYL Summary: Gamma Glutamyl Transferase (GGT) NCD 190.32 The terms of Medicare National Coverage Determinations (NCDs) are binding on all fee-for-service (Part A/B) Medicare Administrative Contractors (MACs) and Medicare Advantage (MA) plans. NCDs are not binding, however, on Medicaid and other governmental payers, nor are they binding on commercial payers in their non-MA lines of business. Item/Service Description* Gamma Glutamyl Transferase (GGT) is an intracellular enzyme that appears in blood following leakage from cells. Renal tubules, liver, and pancreas contain high amounts, although the measurement of GGT in serum is almost always used for assessment of hepatobiliary function. Unlike other enzymes which are found in heart, skeletal muscle, and intestinal mucosa as well as liver, the appearance of an elevated level of GGT in serum is almost always the result of liver disease or injury. It is specifically useful to differentiate elevated alkaline phosphatase levels when the source of the alkaline phosphatase increase (bone, liver, or placenta) is unclear. The combination of high alkaline phosphatase and a normal GGT does not, however, rule out liver disease completely. As well as being a very specific marker of hepatobiliary function, GGT is also a very sensitive marker for hepatocellular damage. Abnormal concentrations typically appear before elevations of other liver enzymes or bilirubin are evident. Obstruction of the biliary tract, viral infection (e.g., hepatitis, mononucleosis), metastatic cancer, exposure to hepatotoxins (e.g., organic solvents, drugs, alcohol), and use of drugs that induce microsomal enzymes in the liver (e.g., cimetidine, barbiturates, phenytoin, and carbamazepine) all can cause a moderate to marked increase in GGT serum concentration. -
Como As Enzimas Agem?
O que são enzimas? Catalizadores biológicos - Aceleram reações químicas específicas sem a formação de produtos colaterais PRODUTO SUBSTRATO COMPLEXO SITIO ATIVO ENZIMA SUBSTRATO Características das enzimas 1 - Grande maioria das enzimas são proteínas (algumas moléculas de RNA tem atividade catalítica) 2 - Funcionam em soluções aquosas diluídas, em condições muito suaves de temperatura e pH (mM, pH neutro, 25 a 37oC) Pepsina estômago – pH 2 Enzimas de organismos hipertermófilos (crescem em ambientes quentes) atuam a 95oC 3 - Apresentam alto grau de especificidade por seus reagentes (substratos) Molécula que se liga ao sítio ativo Região da enzima e que vai sofrer onde ocorre a a ação da reação = sítio ativo enzima = substrato 4 - Peso molecular: varia de 12.000 à 1 milhão daltons (Da), são portanto muito grandes quando comparadas ao substrato. 5 - A atividade catalítica das Enzimas depende da integridade de sua conformação protéica nativa – local de atividade catalítica (sitio ativo) Sítio ativo e toda a molécula proporciona um ambiente adequado para ocorrer a reação química desejada sobre o substrato A atividade de algumas enzimas podem depender de outros componentes não proteicos Enzima ativa = Holoenzimas Parte protéica das enzimas + cofator Apoenzima ou apoproteína •Íon inorgânico •Molécula complexa (coenzima) Covalentemente ligados à apoenzima GRUPO PROSTÉTICO COFATORES Elemento com ação complementar ao sitio ativo as enzimas que auxiliam na formação de um ambiente ideal para ocorrer a reação química ou participam diretamente dela -
Relationship of Liver Enzymes to Insulin Sensitivity and Intra-Abdominal Fat
Diabetes Care Publish Ahead of Print, published online July 31, 2007 Relationship of Liver Enzymes to Insulin Sensitivity and Intra-abdominal Fat Tara M Wallace MD*, Kristina M Utzschneider MD*, Jenny Tong MD*, 1Darcy B Carr MD, Sakeneh Zraika PhD, 2Daniel D Bankson MD, 3Robert H Knopp MD, Steven E Kahn MB, ChB. *Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System 1Obstetrics and Gynecology, University of Washington, Seattle, WA 2Pathology and Laboratory Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA 3Harborview Medical Center, University of Washington, Seattle, WA Running title: Liver enzymes and insulin sensitivity Correspondence to: Steven E. Kahn, M.B., Ch.B. VA Puget Sound Health Care System (151) 1660 S. Columbian Way Seattle, WA 98108 Email: [email protected] Received for publication 18 August 2006 and accepted in revised form 29 June 2007. 1 Copyright American Diabetes Association, Inc., 2007 Liver enzymes and insulin sensitivity ABSTRACT Objective: To determine the relationship between plasma liver enzyme concentrations, insulin sensitivity and intra-abdominal fat (IAF) distribution. Research Design and Methods: Plasma gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alanine transaminase (ALT) levels, insulin sensitivity (SI), IAF and subcutaneous fat (SCF) areas were measured on 177 non-diabetic subjects (75M/102, 31-75 2 -5 years) with no history of liver disease. Based on BMI (< or ≥27.5 kg/m ) and SI (< or ≥7.0x10 min-1 pM-1) subjects were divided into lean insulin sensitive (LIS, n=53), lean insulin resistant (LIR, n=60) and obese insulin resistant (OIR, n=56) groups. -
GFAT and PFK Genes Show Contrasting Regulation of Chitin
www.nature.com/scientificreports OPEN GFAT and PFK genes show contrasting regulation of chitin metabolism in Nilaparvata lugens Cai‑Di Xu1,3, Yong‑Kang Liu2,3, Ling‑Yu Qiu2, Sha‑Sha Wang2, Bi‑Ying Pan2, Yan Li2, Shi‑Gui Wang2 & Bin Tang2* Glutamine:fructose‑6‑phosphate aminotransferase (GFAT) and phosphofructokinase (PFK) are enzymes related to chitin metabolism. RNA interference (RNAi) technology was used to explore the role of these two enzyme genes in chitin metabolism. In this study, we found that GFAT and PFK were highly expressed in the wing bud of Nilaparvata lugens and were increased signifcantly during molting. RNAi of GFAT and PFK both caused severe malformation rates and mortality rates in N. lugens. GFAT inhibition also downregulated GFAT, GNPNA, PGM1, PGM2, UAP, CHS1, CHS1a, CHS1b, Cht1-10, and ENGase. PFK inhibition signifcantly downregulated GFAT; upregulated GNPNA, PGM2, UAP, Cht2‑4, Cht6‑7 at 48 h and then downregulated them at 72 h; upregulated Cht5, Cht8, Cht10, and ENGase; downregulated Cht9 at 48 h and then upregulated it at 72 h; and upregulated CHS1, CHS1a, and CHS1b. In conclusion, GFAT and PFK regulated chitin degradation and remodeling by regulating the expression of genes related to the chitin metabolism and exert opposite efects on these genes. These results may be benefcial to develop new chitin synthesis inhibitors for pest control. Chitin is a linear polymer composed of N-acetylglucosamine units connected by β-1, 4-glycoside bonds and is the second most abundant biopolymer in nature. It is widely distributed in fungi, nematodes, and arthropods1. In insects, chitin is a major component of the exoskeleton, trachea, and the peritrophic matrix that lines the midgut epithelium1–4. -
Alanine Transaminase Assay (ALT) Catalog #8478 100 Tests in 96-Well Plate
Alanine Transaminase Assay (ALT) Catalog #8478 100 Tests in 96-well plate Product Description Alanine Aminotransferase (ALT), also known as serum glutamic-pyruvic transaminase (SGPT), catalyzes the reversible transfer of an amino group from alanine to α-ketoglutarate. The products of this transamination reaction are pyruvate and glutamate. ALT is found primarily in liver and serum, but occurs in other tissues as well. Significantly elevated serum ALT levels often suggest the existence of medical problems, such as hepatocellular injury, hepatitis, diabetes, bile duct problem and myopathy. This colorimetric assay is based on the oxidization of NADH to NAD in the presence of pyruvate and lactate dehydrogenase. The ALT activity is determined by assaying the rate of NADH oxidation, which is proportional to the reduction in absorbance at 340nm over time (ΔOD340nm/min). Kit Components Cat. No. # of vials Reagent Quantity Storage 8478a 1 Assay buffer 10 mL -20°C 8478b 1 ALT standard 10 µL -20°C 8478c 1 Substrate mix 1.0 mL -20°C 8478d 1 Cofactor 0.8 mL -20°C 8478e 1 Enzyme 0.2 mL -80°C Product Use The ALT kit measures the alanine transaminase activity of different types of samples, such as serum, plasma and tissues. ALT is for research use only. It is not approved for human or animal use, or for application in in vitro diagnostic procedures. Quality Control Serially diluted alanine transaminase solutions with concentrations ranging from 0.03125 to 1.0 U/mL are measured with the ScienCell™ Alanine Transaminase Assay kit. The decrease in OD340nm is monitored as a function of time (Figure 1) and the resulting standard of ∆OD340nm/min vs alanine transaminase activity are plotted (Figure 2). -
Pyridoxine (Pyridoxamine) 5'-Phosphate Oxidase In
PYRIDOXINE (PYRIDOXAMINE) 5’-PHOSPHATE OXIDASE IN ARABIDOPSIS THALIANA Except where reference is made to the work of others, the work described in this dissertation is my own or was done in collaboration with my advisory committee. This dissertation does not include proprietary or classified information. Yuying Sang Certificate of Approval: Robert D. Locy Narendra K. Singh, Chair Professor Professor Biological Sciences Biological Sciences Joe H. Cherry Joanna Wysocka-Diller Emeritus Professor Associate Professor Biological Sciences Biological Sciences Fenny Dane George T. Flowers Professor Dean Horticulture Graduate School PYRIDOXINE (PYRIDOXAMINE) 5’-PHOSPHATE OXIDASE IN ARABIDOPSIS THALIANA Yuying Sang A Dissertation Submitted to the Graduate Faculty of Auburn University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Auburn, Alabama December 19, 2008 PYRIDOXINE (PYRIDOXAMINE) 5’-PHOSPHATE OXIDASE IN ARABIDOPSIS THALIANA Yuying Sang Permission is granted to Auburn University to make copies of this dissertation at its discretion, upon request of individuals of institutions and at their expense. The author reserves all publication right. Signature of Author Date of Graduation iii VITA Yuying Sang, daughter of Shiqing Sang and Guilan Wang, was born on January 7, 1975, in Chiping, Shandong, People’s Republic of China. She received the Bachelor of Science degree in Biology in July 1997 from Shandong Normal University and entered the Graduate School of Kunming Institute of Botany, Chinese Academy of Sciences. In the July of 2000, she graduated with a Master of Science degree in Botany and joined East China University of Science and Technology as a lab manager in the Department of Bioengineering. -
Cholesterol Metabolism and Statin Effects on an FH Class II LDL-Receptor Mutation." (2018)
University of Louisville ThinkIR: The University of Louisville's Institutional Repository Electronic Theses and Dissertations 12-2018 Cholesterol metabolism and statin effects on an FH class II LDL- receptor mutation. Linda Omer University of Louisville Follow this and additional works at: https://ir.library.louisville.edu/etd Part of the Cardiovascular Diseases Commons, Medical Molecular Biology Commons, and the Other Medical Sciences Commons Recommended Citation Omer, Linda, "Cholesterol metabolism and statin effects on an FH class II LDL-receptor mutation." (2018). Electronic Theses and Dissertations. Paper 3080. https://doi.org/10.18297/etd/3080 This Doctoral Dissertation is brought to you for free and open access by ThinkIR: The University of Louisville's Institutional Repository. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of ThinkIR: The University of Louisville's Institutional Repository. This title appears here courtesy of the author, who has retained all other copyrights. For more information, please contact [email protected]. CHOLESTEROL METABOLISM AND STATIN EFFECTS ON AN FH CLASS II LDL-RECEPTOR MUTATION By Linda Omer B.S., Chicago State University, 2011 M.S., Chicago State University, 2014 M.S., University of Louisville, 2015 A Dissertation Submitted to the Faculty of the School of Medicine of the University of Louisville In Partial Fulfillment of the Requirements For the Degree of Doctor of Philosophy in Biochemistry and Molecular Genetics Department of Biochemistry and Molecular Genetics University of Louisville Louisville, KY December 2018 2018 by Linda Omer All rights reserved CHOLESTEROL METABOLISM AND STATIN EFFECTS ON AN FH CLASS II LDL-RECEPTOR MUTATION By Linda Omer B.S., Chicago State University, 2011 M.S., Chicago State University, 2014 M.S., University of Louisville, 2015 A Dissertation Approved on November 9, 2018 By the following Dissertation Committee: Nolan L. -
Variants of Phosphohexose Isomerase in Gastrointestinal And
[CANCER RESEARCH 48. 2998-3001, June, 1988] Variants of Phosphohexose Isomerase in Gastrointestinal and Mammary Carcinoma: Isoelectric Focusing Patterns of Normal and Tumor Tissues Derived from Surgical Specimens of the Same Patient1 Matthias Baumann, Damián Jezussek, Ralf-Torsten Richter, and Karl Brand2 Institute of Biochemistry, Medical Faculty, University of Erlangen-Nuremberg, Federal Republic of Germany ABSTRACT H2PO4 H2O, 5; MgSO4 7H2O,0.77; Krebs saline buffer: H2O, 1:4; pH 7.5). The occurrence of charge variants of phosphohexose isómeras? was Then the homogenate was sonicated by 6 pulses of 10 s each at 50 elucidated in cancerous and, for comparison, in noncancerous tissues W with cooling intervals of 1 min to make sure that the temperature of the preparation remained below 10'C. Subsequently, the extract was obtained from the same organ. Surgical specimens from 35 patients with gastrointestinal and mammary carcinoma were studied by means of the rehomogenized and centrifuged at 12,000 x g for 10 min. The super isoelectric focusing (IEF) technique. Differences in the IEF pattern could natant was dialyzed against 1% glycine buffer, pH 7.5, overnight at 4'C. LKB Multiplier 2117, LKB Power Supply Unit 2103, and Servalyt be demonstrated in 90% of the patients with gastric cancer. Correspond ing values for the patients with colorectal and mammary carcinoma were Precotes, pH 3-10, were used for the isoelectric focusing experiments. 50 and 73%, respectively. Almost all normal specimens proved to be A Julabo Paratherm FT20p electronic thermostat served to cool the plate to 4'C during the run. monomorphic, revealing only the major basic band with a pi of 9.1. -
Lipid Screening in Childhood and Adolescence for Detection of Multifactorial Dyslipidemia
Supplementary Online Content Lozano P, Henrikson NB, Morrison CC, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia: evidence report and systematic review for the US Preventive Services Task Force. JAMA. doi:10.1001/jama.2016.6423 eMethods. Literature Search Strategies eTable. Quality Assessment Criteria eFigure. Literature Flow Diagram This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 eMethods. Literature Search Strategies Search Strategy Sources searched: Cochrane Central Register of Controlled Clinical Trials, via Wiley Medline, via Ovid PubMed, publisher-supplied Key: / = MeSH subject heading $ = truncation ti = word in title ab = word in abstract adj# = adjacent within x number of words pt = publication type * = truncation ae = adverse effects ci = chemically induced de=drug effects mo=mortality nm = name of substance Cochrane Central Register of Controlled Clinical Trials #1 (hyperlipid*emia*:ti,ab,kw or dyslipid*emia*:ti,ab,kw or hypercholesterol*emia*:ti,ab,kw or hyperlipoprotein*emia*:ti,ab,kw or hypertriglycerid*emia*:ti,ab,kw or dysbetalipoprotein*emia*:ti,ab,kw) #2 (familial next hypercholesterol*emi*):ti,ab,kw or (familial next hyperlipid*emi*):ti,ab,kw or (essential next hypercholesterol*emi*):ti,ab,kw or (familial near/3 apolipoprotein):ti,ab,kw #3 "heterozygous fh":ti,ab,kw or "homozygous fh":ti,ab,kw