bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular-specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury in mice
Authors: Nace Gary W. , Huang Hai , Klune John R. , Eid Raymond E. , Rosborough Brian R. , Korff Sebastian , Li Shen , Shapiro Richard A. , Stolz Donna B. , Sodhi Chhinder P. , Hackam David J. , Geller David A. , Billiar Timothy R. , Tsung Allan 
Published: March 2013

Abstract

Ischemia-reperfusion (I/R) injury is a process whereby an initial hypoxic insult and subsequent return of blood flow leads to the propagation of innate immune responses and organ injury. The necessity of the pattern recognition receptor, Toll-like receptor (TLR)4, for this innate immune response has been previously shown. However, TLR4 is present on various cell types of the liver, both immune and nonimmune cells. Therefore, we sought to determine the role of TLR4 in individual cell populations, specifically, parenchymal hepatocytes (HCs), myeloid cells, including Kupffer cells, and dendritic cells (DCs) subsequent to hepatic I/R. When HC-specific (Alb-TLR4−/−) and myeloid-cell–specific (Lyz-TLR4−/−) TLR4 knockout (KO) mice were subjected to warm hepatic ischemia, there was significant protection in these mice, compared to wild type (WT). However, the protection afforded in these two strains was significantly less than global TLR4 KO (TLR4−/−) mice. DC-specific TLR4−/− (CD11c-TLR4−/−) mice had significantly increased hepatocellular damage, compared to WT mice. Circulating levels of high-mobility group box 1 (HMGB1) were significantly reduced in Alb-TLR4−/− mice, compared to WT, Lyz-TLR4−/−, CD11c-TLR4−/− mice and equivalent to global TLR4−/− mice, suggesting that TLR4-mediated HMGB1 release from HCs may be a source of HMGB1 after I/R. HCs exposed to hypoxia responded by rapidly phosphorylating the mitogen-activated protein kinases, c-Jun-N-terminal kinase (JNK) and p38, in a TLR4-dependent manner; inhibition of JNK decreased release of HMGB1 after both hypoxia in vitro and I/R in vivo. Conclusion: These results provide insight into the individual cellular response of TLR4. The parenchymal HC is an active participant in sterile inflammatory response after I/R through TLR4-mediated activation of proinflammatory signaling and release of danger signals, such as HMGB1. (HEPATOLOGY 2013)
Book Reviews
Authors: PROCITA LEONARD 
Published: March 2013

Book reviewed in this article:Diuresis, Kaliuresis, and Hypertension: Long‐Term Clinical Experience With a Fixed Combination of Amiloride Hydrochloride and Hydrochlorothiazide. Bruno Magnani, editor.Lithium in Psychiatry—A Synopsis. A. Villeneuve, editor. Quebec, Canada, Les Presses de L'Université Laval. 1976. 205 pages. No price given.Antibiotics. A Critical Review. W. Kurylowicz, editor. Warsaw, Poland, Polish Medical Publishers. (American Society For Microbiology, Washington, D.C.). 1976. 204 pages. No price given.
Book Reviews
Authors: PROCITA LEONARD 
Published: March 2013

Book reviewed in this article:Natriuretic Hormone. H. J. Kramer and F. KrückChemoreception in the Carotid Body. H. Acker, S. Fidone, D. Pallot, C. Eyzaguirre, D. W. Lubbers, and R. W. TorranceAntiviral Agents and Viral Diseases of Man. J. Galasso, T. C. Merigan, and R. A. Buchanan
Book Reviews
Authors: PROCITA LEONARD 
Published: March 2013

Book reviewed in this article:Contemporary Standards for Antimicrobial Usage. W. R. McCabe and M. Finland, editors. (Principles and Techniques of Human Research and Therapeutics, F. Gilbert McMahon, editor).Cardiac Glycosides. G. Bodem and H. J. Dengler.Cardiovascular Pharmacology. Michael J. Antonaccio, editor.Antiarrhythmic, Antihypertensive and Lipid Lowering Drugs. Cardiovascular Drugs, Volume 1. Graeme S. Avery, series editor.Immunotherapy of Cancer: Present Status of Trials in Man. Progress in Cancer Research and Therapy, Vol. 6. W. D. Terry and D. Windhorst, editors.Control of Neoplasia by Modulation of the Immune System. Progress in Cancer Research and Therapy, Vol. 2. Michael A. Chirigos, editor.GLC and HPLC Determination of Therapeutic Agents, Part 1. Chromatographic Science Series, Vol. 9. K. Tsuji and W. Morozowich, editors.
Book Reviews
Authors: PROCITA LEONARD 
Published: March 2013

Book reviewed in this article:Cutting's Handbook of Pharmacology, 6th Edition. C. Z. Csaky.Introductory Medicinal Chemistry. J.B. Taylor and P.D. Kennewell.Microsomes, Drug Oxidations, and Chemical Carcinogenesis. M. J. Coon, A. H. Conney, R. W. Estabrook, H. V. Gelboin, J. R. Cillette, and P. J. O'Brien, editors.GLC and HPLC Determination of Therapeutic Agents, Part 2. Chromatographic Science Series, Vol. 9. K. Tsuji, editor.GLC and HPLC Determination of Therapeutic Agents, Part 3. Chromatographic Science Series, Vol. 9. K. Tsuji, editor.Neuropsychiatric Side Effects of Drugs in the Elderly. A. J. Levenson, editor.
Medroxalol Combined with Hydrochlorothiazide in the Treatment of Hypertension
Authors: VLACHAKIS NICOLAS D. , ELASQUEZ MANUEL , ALEXANDER NATALIE , MARONDE ROBERT F. 
Published: March 2013

Abstract: The antihypertensive effect and safety of hydrochlorothiazide administration as a single drug and together with medroxalol were determined in 20 patients with primary hypertension. Following two biweekly intervals on placebo and hydrochlorothiazide, medroxalol was started at 100 mg three times a day and titrated against blood pressure response up to a maximum of 300 mg three times a day. In nine patients the effect of the single and the combined drug therapy on blood pressure during isometric handgrip exercise, on plasma renin activity, and on plasma catecholamines and their deaminated metabolites was investigated.The administration of hydrochlorothiazide was associated with a significant decrease in blood pressure, but heart rate did not change. The addition of medroxalol produced a substantial decrease in blood pressure and heart rate in both the recumbent and upright positions (P < 0.001). Due to careful titration of medroxalol, orthostatic hypotension was observed only in one patient. Neither hydrochlorothiazide alone nor the combined drug regimen prevented or diminished the rise in blood pressure with exercise. Although plasma renin activity decreased during the combined drug therapy, there was no correlation between the initial levels or the change in plasma renin activity and the extent of decrease in blood pressure. The concentration of plasma epinephrine increased during the combined drug period, whereas catecholamine metabolites increased significantly during both periods of the study. It is concluded that medroxalol combined with hydrochlorothiazide constituted a potent and safe antihypertensive therapy for the duration of the present study.
Methyldopa Does Not Alter the Disposition of Digoxin
Authors: MAY CAROL A. , VLASSES PETER H. , ROCCI MARIO L. , ROTMENSCH HESCHI H. , SWANSON BRIAN N. , TANNENBAUM RENEE P. , FERGUSON ROGER K. , ABRAMS WILLIAM B. 
Published: March 2013

Recent reports have documented interactions between digoxin and agents with dissimilar chemical structures, including quinidine,1–3 nifedipine,4 verapamil,5,6 and amiodarone.7,8 Concomitant use of these agents with digoxin has resulted in increased serum concentrations and, in some cases, clinical signs and symptoms of digoxin toxicity. On this basis, the Food and Drug Administration has proposed that future New Drug Applications for drugs that have projected use in the elderly should contain evaluations of digoxin interactions.Methyldopa (Aldomet, Merck Sharp & Dohme) is a commonly prescribed antihypertensive agent which is frequently administered concomitantly with digoxin. The purpose of this study was to evaluate whether methyldopa alters the disposition of digoxin in normal volunteers.
Comparison of Antimanic Efficacy of Clonidine and Verapamil
Authors: Giannini A. James , Loiselle Robert H. , Price William A. , Giannini Matthew C. 
Published: March 2013

The standard treatment for mania has been lithium carbonate, alone or in combination with neuroleptics. Unfortunately, lithium is refractory in some patients and may possess potential thyroid and renal toxicity.1 Neuroleptics also are not without risks and can cause extrapyramidal symptoms as well as tardive dyskinesia.2 As a result, other less potentially troubling agents have been sought to control the symptoms of mania. Two such drugs are the antihypertensive agent, clonidine, and the antianginal drug, verapamil.Clonidine is an alpha2 agonist. It exerts central pharmacologic effects by stimulating inhibitory auto‐receptors.2 This reduction in noradrenergic activity has proven useful in reducing tension and nervousness associated with opiate withdrawal,3 and panicanxiety disorders.4 Clonidine has also been used successfully as an antimanic drug in two separate trials.5,6 This has been hypothesized to be a result of reduction in the hypernoradrenergic tone associated with mania.6,7Verapamil, a slow‐channel calcium blocker, has also been shown to be effective in reducing manic symptoms.8,9 In addition to blocking calcium influx in myocardial cells, it inhibits neurosecretory processes including excitation‐secretion coupling at noradrenergic synapses.10 Verapamil's action on calcium metabolism may mimic lithium's; both drugs block adenyl cyclase activity in most organ systems and as well as competing with calcium ions in neuromuscular cells.11 Calcium metabolism is of interest, since the onset of manic episodes are associated with transient increases in serum calcium.12Since clonidine and verapamil are both cardiovascular drugs as well as putative antimanic agents, the authors thought it appropriate to compare their antimanic effects in the double‐blind, crossover study described below.
Therapeutic Manipulations in Uremic Bleeding
Authors: Watson Alan J. , Whelton Andrew 
Published: March 2013

Currently 80,000 patients are maintained by chronic dialysis in the United States, a figure that, however, only represents a small fraction of the overall population who experience acute or chronic impairment in renal function. It is well recognized that such patients with acute or chronic renal failure exhibit an increased tendency to bleed.1 The clinical significance of this complication is that hemorrhagic episodes remain a major contributory factor to the morbidity and mortality associated with uremia.2 Mucosal bleeding, particularly of the gastrointestinal tract, is perhaps the most frequent manifestation of the hemorrhagic diathesis; other manifestations include ecchymoses, epistaxis, hemorrhagic pericarditis, and subdural hematoma. The incidence of gastrointestinal hemorrhage in patients with established acute renal failure is approximately 30% to 40%,3 and in one major study accounted for 30% of the overall mortality.2 In the setting of chronic renal failure, hemorrhagic complications tend to be more frequent than those recorded in acute renal failure with an incidence of 60% in nondialyzed patients and 75% in dialyzed patients.4 In view of the impressive morbidity associated with this complication of acute and chronic renal failure, new approaches to the management of uremic bleeding merit brief commentary.Definition of the principal hemostatic defect remains elusive despite the fact that several abnormalities of primary hemostasis have been detected. These include defective platelet factor‐Ill generation,5 subnormal platelet aggregation,6 prostacyclin/thromboxane A2 imbalance,7,8 and alterations in the activities of certain coagulation factors.9 Of the various laboratory tests available for assessing hemostasis, the bleeding time, which reflects the combined effects of (1) platelet function; (2) factor VIII: von Willebrand's factor (FVIII:VWF) activity; (3) hematocrit; and (4) vascular contractility, appears to correlate best with the likelihood of actual clinical hemorrhage in the uremic patient.10
Reliability of Theophylline Clearance in Determining Maintenance Intravenous Aminophylline Therapy
Authors: Grambau Geoffrey R. , Johnson Cary E. , Conlon Paul F. , Weg John G. 
Published: March 2013

Although theophylline has long been the primary drug used for the management of reversible obstructive airway disease, current recommendations for determining theophylline dosage have not been dependable and, when applied to individual patients, have resulted in a wide range of serum theophylline concentrations (STC) and frequent adverse reactions.1–3The objective of this study was to evaluate the clinical reliability of using theophylline clearance values to adjust the theophylline infusion rate to achieve a desired STC and to determine the minimum time required for administration of a continuous theophylline infusion in a given population of patients before obtaining a single STC for the clinically reliable calculation of theophylline clearance.
The Effect of Rapid Digitalization on Ventricular Function in Patients With Congestive Heart Failure
Authors: Rotenberg Zvi , Hellman Chaim , Weinberger Itzhak , Fuchs Jacob , Agmon Jacob 
Published: March 2013

Cardiac glycosides have been used in the treatment of cardiac failure for more than 200 years. Digitalis and its analogues have been shown to increase myocardial contractility and to decrease left ventricular end‐diastolic pressure and volume, while causing no essential change in aortic pressure and a variable decrease in heart rate.1–2 However, several reports3–8 have questioned the use of digitalis in patients with ventricular dysfunction, particularly in view of the newer modes of therapy.The aim of this study was to define the effects of rapid digitalization on left and right ventricular function in patients with chronic congestive heart failure, using radionuclide methods.
BOOK REVIEW
Authors: Cavaliere Beth 
Published: March 2013

Book reviewed in this article:Unstable Angina: A Clinical Approach by G. PlotnickSecond SCI‐RSC Medicinal Chemistry Symposium edited by J. C. EmmettChemistry of the Prostaglandins and Leukotrienes (Advances in Prostaglandin, Thromboxane, and Leukotriene Research, vol 14), edited by John E. Pike and Douglas R. Morton, JrThymic Factor Therapy (Serono Symposia Publications from Raven Press, vol 16), edited by N. A. Byrom and J. R. HobbsPlatelets, Prostaglandins, and the Cardiovascular System (Advances in Prostaglandin, Thromboxane, and Leukotriene Research, vol 13), edited by Gian G. Neri Serneri, John C. McGiff, Rodolfo Paoletti, and Gustav V. R. BornDual Regulation of Adenylate Cyclase (Advances in Cyclic Nucleotide and Protein Phosphorylation Research, vol 19), edited by Dermot M. F. Cooper and Kenneth B. SeamonSerotonin and the Cardiovascular System edited by Paul M. Vanhoutte
Book Reviews
Authors: Cavaliere M. Beth 
Published: March 2013

Book reviewed in this article:Epilepsy and GABA Receptor Agonists: Basic and Therapeutic Research, (L.E.R.S. Monograph Series, Vol 3) edited by G. Bartholini, L. Bossi, K. G. LloydOptimization of Drug Delivery: Alfred Benzon Symposium 17 edited by H. Bundgaard, A. B. Hansen, and H. Kofod
Book Reviews
Authors: Cavaliere M. Beth 
Published: March 2013

Book reviewed in this article:Variability in Drug Therapy: Description, Estimation, and Control edited by Malcolm Rowland, Lewis B. Sheiner, and Jean‐Louis SteimerChronic Treatments in Neuropsychiatry (Advances in Biochemical Psychopharmacology, Volume 40), Edited by Dargut Kemali and Giorgio Racagni
BOOK REVIEWS
Authors: Cavaliere M. Beth 
Published: March 2013

Book reviewed in this article:Brain Reward Systems and Abuse Edited by Jorgen Engel et alLogan's Medical and Scientific Abbreviations Carol ynn M. Logan and M. Katherine Rice, J. B. LippincottSenile Dementia of the Alzheimer Type Edited by J. Traber and W. H. Gispin
BOOK REVIEWS
Authors: Cavaliere M. Beth 
Published: March 2013

Book reviewed in this article:Drug Evaluations, Sixth Edition American Medical Association, Department of Drugs, Division of Drugs and Technology in Cooperation with the American Society for Clinical Pharmacology and Therapeutics.Drugs for the Heart (Second Expanded Edition) Edited by Lionel H. OpieDrugs for the Respiratory System Edited by Reuben M. CherniackGuide to Clinical Interpretation of Data By Bert Spilker
Ambient ion/molecule reactions in low‐temperature plasmas (LTP): reactive LTP mass spectrometry
Authors: Benassi Mario , Garcia‐Reyes Juan F. , Spengler Bernhard 
Published: March 2013

RATIONALEIon/molecule reactions are commonly used to characterize structures due to their high specificity. Herein, we present ambient ion/molecule reactions performed in the course of low‐temperature plasma (LTP) ionization of condensed‐phase analytes in order to increase the specificity of LTP‐based ambient analysis.METHODSThe ion population of the cold plasma is modified by addition of a reagent to the plasma before it is directed at a surface bearing the analyte. Desorbed ions were analyzed using linear ion trap‐Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS).RESULTSAcylium ions generated from tetramethylurea react with 1,3‐dioxane analyte to afford distinctive Eberlin product ions. Reactions of alkylamines, such as n‐hexylamine and n‐octylamine, with benzaldehyde produce the corresponding imines. Reaction of ruthenocene with trifluoroacetic anhydride forms the unusual trifluoroacetate ruthenocene.CONCLUSIONSA LTP source can be used to generate reagent ions that can undergo ion/molecule reactions in the ambient environment with an analyte at condensed phase on a surface. The experiment is a 'reactive' version of the standard low‐temperature plasma (LTP) ambient ionization experiment. This approach provides additional information by combining ion/molecule chemistry with conventional MS and MS/MS data to characterize particular analytes. Copyright © 2013 John Wiley & Sons, Ltd.
Structural characterization of biocompatible lipoic acid–oligo‐(3‐hydroxybutyrate) conjugates by electrospray ionization mass spectrometry
Authors: Maksymiak Magdalena , Debowska Renata , Jelonek Katarzyna , Kowalczuk Marek , Adamus Grazyna 
Published: March 2013

RATIONALECurrently, most of the antioxidants and free radical neutralizers used in cosmetic compositions are absorbed quickly into deeper layers of skin, and then carried away by the blood stream. It would be beneficial to delay the penetration of antioxidants to the deeper layers of skin to control their delivery and release.METHODSRecently, growing attention has been paid to the attachment of cosmetics to specific polymer carriers. Biodegradable and biocompatible conjugates of oligo‐3‐hydroxybutyrate with lipoic acid were obtained via the anionic ring‐opening oligomerization of (R,S)‐β‐butyrolactone initiated by lipoic acid potassium salt. The structure of the resulting conjugates as well as their water‐soluble hydrolytic degradation products were established at the molecular level by electrospray ionization mass spectrometry (ESI‐MSn) supported by 1H NMR analyses.RESULTSThe structural studies, performed with the aid of ESI‐MSn, confirmed that the lipoic acid was covalently bound to oligo‐3‐hydroxybutyrate chains through hydrolyzable ester bonds. Furthermore, hydrolytic degradation studies of the bioconjugates provided detailed insight into the hydrolysis process, allowing the identification of the degradation products and confirming the release of α‐lipoic acid. Cytotoxicity tests demonstrated that the conjugates were non‐toxic.CONCLUSIONSDetailed molecular structural studies of new polymeric delivery systems of lipoic acid were performed by ESI‐MS. ESI‐MS proved to be an excellent technique for the evaluation of hydrolytic degradation products of the conjugates and for monitoring the release of lipoic acid. The results obtained contribute significantly to the characterization of biocompatible LA‐OHB conjugates with potential applications in cosmetology. Copyright © 2013 John Wiley & Sons, Ltd.
Mass spectrometric characterization of organosulfates related to secondary organic aerosol from isoprene
Authors: Safi Shalamzari Mohammad , Ryabtsova Oxana , Kahnt Ariane , Vermeylen Reinhilde , Hérent Marie‐France , Quetin‐Leclercq Joëlle , Van der Veken Pieter , Maenhaut Willy , Claeys Magda 
Published: March 2013

RATIONALEA considerable fraction of atmospheric particulate fine matter consists of organosulfates, with some of the most polar ones originating from the oxidation of isoprene. Their structural characterization provides insights into the nature of gas‐phase precursors as well as into formation pathways.METHODSThe structures of unknown polar organosulfates present in ambient particulate fine matter were characterized using liquid chromatography/(−)electrospray ionization mass spectrometry (LC/(−)ESI‐MS), including ion trap MSn and accurate mass measurements, derivatization of the carbonyl group into 2,4‐dinitrophenylhydrazones, detailed interpretation of the MS data, and in a selected case comparison of their LC and MS behavior with that of synthesized reference compounds.RESULTSPolar organosulfates with molecular weights (MWs) of 156, 170, 184 and 200 were attributed to/or confirmed as derivatives of glycolic acid (156), lactic acid (170), 1,2‐dihydroxy‐3‐butanone (184), glycolic acid glycolate (200), 2‐methylglyceric acid (200), and 2,3‐dihydroxybutanoic acid (200). In the case of the MW 184 compound an unambiguous assignment was obtained through synthesis of reference compounds.CONCLUSIONSA more complete structural characterization of polar organosulfates that originate from isoprene secondary organic aerosol was achieved. An important atmospheric finding is the presence of an organosulfate that is related to methyl vinyl ketone, a major gas‐phase oxidation product of isoprene. In addition, minor polar organosulfates related to crotonaldehyde were identified. Copyright © 2013 John Wiley & Sons, Ltd.
Analysis of novel melphalan hydrolysis products formed under isolated lung perfusion conditions using liquid chromatography/tandem mass spectrometry
Authors: Boschmans Jasper , de Bruijn Ernst , Van Schil Paul , Lemière Filip 
Published: March 2013

RATIONALEMelphalan is a widely used cytotoxic agent in cancer treatments. This phenylalanine analog has been shown an effective drug in the treatment of breast cancer, multiple myeloma and melanoma of the extremities. A good knowledge of the drug's degradation and metabolism are crucial for understanding its activity during cancer treatments.METHODSThe formation of hydrolysis products of melphalan is studied using ultra‐performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS). Aqueous melphalan solutions were incubated at elevated temperatures and analyzed by UPLC/MS/MS. Two previously described hydrolysis products, mono‐ and dihydroxymelphalan (MOH and DOH), were formed in vitro and could be characterized during MS/MS and high‐resolution experiments.RESULTSNovel compounds with m/z values >500 Da were discovered. Comparison of the fragmentation patterns of these new molecules with those of MOH and DOH show great similarities. The higher masses are explained by the presence of two or more melphalan units. In total, more than 15 new hydrolysis products were found. Experiments were set up to study the formation and the chemical structures of these molecules.CONCLUSIONSThe hydrolysis of melphalan is studied in the scope of a phase II clinical trial (isolated lung perfusion, ILuP). Patient samples were screened for the presence of all documented and novel melphalan hydrolysis products. This study reports the formation of a new class of oligomeric compounds in both in vivo and in vitro samples. Copyright © 2013 John Wiley & Sons, Ltd.