bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of Gold Thread Implantation for Crow's Feet
Authors: Shin Kee Cheol , Bae Tae Hui , Kim Woo Seob , Kim Han Koo 
Published: February 2012

Background Conservative techniques designed to block or delay the aging process have been utilized in various ways for many years. However, their effects can be relatively minimal and short-term in most cases compared to surgery. The objective of this study was to evaluate the efficacy and safety of gold thread implantation for the treatment of periorbital wrinkles.
Methods A total of 78 consecutive patients who showed mild to severe periorbital wrinkles were deemed appropriate candidates, including 69 women and 9 men ranging from 31 to 59 years (mean, 47 years). Six gold threads about 4 cm in length were inserted subdermally in each patient at intervals of about 0.5 cm. Follow-up assessments were performed 1, 4, and 12 weeks after the procedure. The efficacy was rated by the physician using the Wrinkle Severity Rating Scale and patients who made global assessments of changes in periorbital wrinkles using the Visual Analog Scale. Adverse events were monitored throughout the course of the study.
Results The patients showed significant improvements after the procedure. There were minor complications such as foreign body sensation in the eye (2.63%) and eye pain (1.32%) that improved spontaneously without any specific treatments.
Conclusions Subdermal implantation of gold thread improves the appearance of periorbital wrinkles and does not appear to have serious side effects. Insertion of gold thread may be an effective and safe method for facial rejuvenation.
Analysis of Scientific Papers Included in the Sciences Citation Index Expanded Written by South Korean Plastic Surgeons: 2001-2010
Authors: Go Ju Young , Mun Goo-Hyun , Jeon Byung-Joon , Lim So-Young , Pyon Jai-Kyong , Bang Sa-Ik , Oh Kap Sung , Shin Myoung-Soo 
Published: February 2012

Background The purpose of our study was to analyze scientific papers published by South Korean plastic surgeons in journals included in the Science Citation Index Expanded (SCIE), and to evaluate the publication and research activities of Korean plastic surgeon.
Methods We conducted a survey of SCIE papers in the field of plastic surgery published by South Korean authors between 2001 and 2010 using Web of Science software. We further analyzed these results according to the number of publications per year, journals, institution, and type of papers. We also compared the total number of citations to published scientific papers. We analyzed the rank of South Korea among other countries in representative journals.
Results Overall, 667 papers were published by South Korean authors between 2001 and 2010. The number of publications increased dramatically from 2003 (n=31) to 2010 (n=139). Subsequently, the ten most productive Korean medical colleges were identified. All published papers received 2,311 citations and the citation to paper ratio was 3.49. The rank of Korea among other countries in terms of the number of published papers remained in the top 10 during the recent 10 years.
Conclusions Publication output of Korean plastic surgeon over the last 10 years showed a remarkable growth in terms of quantity and quality. Currently, Korea is among the top six countries in representative plastic surgery journals. Korean plastic surgeons have played a central role in this progress, and it is anticipated that they will continue to do so in the future.
Mouse Models of Atherosclerosis
Authors: Maganto‐Garcia E. , Tarrio M. , Lichtman A.H. 
Published: February 2012

AbstractGenetically altered mice carrying mutations of genes encoding crucial components of the immune system and lipid metabolism have been widely used to study the role of immune responses and inflammation in atherosclerosis. These mice are often fed a diet, with a high content of cholesterol and saturated fat in order to induce hypercholesterolemia and arterial lesions. We review the different mouse models of atherosclerosis, type of diets, and techniques to measure lipid deposition and lesion size in the arterial walls. Moreover, the methods used to determine the presence of the immune cells in atherosclerotic lesions are also described here. Curr. Protoc. Immunol. 96:15.24.1‐15.24.23. © 2012 by John Wiley & Sons, Inc.
Oral Absorption: from Physiology to Regulatory
Authors: Berlioz‐Seux Fran 
Published: February 2012

AbstractIntestinal absorption consists of the sum of multiple processes. First, solubility, dissolution rate, lipophilicity, pKa(negative logarithm of the acid dissociation constant,Ka), and molecular weight (MW) are major physicochemical properties driving the absorption potential of a drug. The drug's permeability is a major determinant of its ability to be absorbed in the intestine. Intestinal absorption can occur through different mechanisms. Within the “rule of 5” chemical space, drugs are usually absorbed through a passive process. Also, intestinal transporters could either hinder or promote a molecule's absorption and can lead to drug‐drug interactions (DDIs).In vitroandin vivotools exist to study intestinal absorption. These tools provide data with different degrees of granularity and with distinct human absorption predictability. Finally, the Food and Drug Administration (FDA) has developed guidelines to assess molecules' properties in terms of intestinal absorption and potential of DDIs.
Bioavailability and Bioequivalence
Authors: Amore Benny M. 
Published: February 2012

AbstractFrom a pharmacokinetic perspective, bioavailability relates systemic exposure to drug absorption, while helping understand mechanisms underlying drug distribution, transport, and metabolism. Bioavailability studies are also designed to demonstrate bioequivalence of test and reference formulations for both new drug and generic drug products. This chapter provides an overview of the interrelated concepts of bioavailability and bioequivalence and their application to characterize human drug disposition. Additionally, for oral drugs, the determinants of bioavailability leading to malabsorption and presystemic elimination by the gut mucosa and liver are described.
Interspecies Pharmacokinetic Scaling and the Prediction of Human Pharmacokinetics Using Animal and Cell Models
Authors: Feng Meihua Rose , Zheng Nan , Zhang Xinyuan , Huh Yea Min , Yu Jing‐yu 
Published: February 2012

AbstractThe allometric scaling is an empirical method developed based on cross‐species similarities in anatomy, physiology, and biochemistry, with a power function correlating physiological parameters with body size (Y = aWb). This method has been used successfully to describe a number of physiological and anatomical properties and has been applied to the projection of human pharmacokinetic (PK) for small‐molecule drugs and therapeutic proteins. However, for most small‐molecule drugs with high cross‐species variability in hepatic metabolism, this method may not work well in the extrapolation of hepatic metabolic clearance from laboratory animals to humans. To improve the predictability of metabolic clearance in humans, several modified scaling methods using (i) maximum life span potential (MLP), (ii) brain weight (BRW), or (iii) liver blood flow (LBF) as a correction factor, or (iv) integration of thein vitrodata into the power function by normalizing thein vivoclearance within vitrometabolic clearance as correction factors have been recommended and tested. These modified scaling methods have improved the accuracy of prediction to some extent and are reviewed in this chapter. In recent years, there is an increasing interest in physiologically based pharmacokinetic (PBPK) and cell‐based pharmacokinetic (CBPK) pharmacokinetic modeling. Both approaches are developed based on the similar assumption that PK properties could be scaled up from animals to humans according to fundamental physiological principles. These advanced methods allow the integration of input information from different sources (e.g., physiological and physicochemical properties of a drug molecule, permeability and binding affinity fromin vitroexperiments, PK profiles from animal tests and clinical trials). In addition to the prediction of PK parameters (e.g., clearance, volume of distribution), the PBPK and CBPK models could also predict the concentration–time profiles in human blood as well as in tissues associated with efficacy and/or toxicity. The utility of PBPK and CBPK modeling goes beyond the prediction of “first‐in‐human trial,” as it has the potential to be continuously updated with new information (physiological and drug related). Some of the tools and techniques employed in PBPK and CBPK modeling are discussed in the second half of this chapter.
ADME of Anticancer Drugs
Authors: Yamazaki Hiroshi 
Published: February 2012

AbstractPolymorphic cytochrome P450 enzymes are responsible for the activation or inactivation of anticancer drugs. Tegafur and letrozole are activated and deactivated by polymorphic P450 2A6, respectively. Tamoxifen treatment and irinotecan labeling are closely related to polymorphisms of P450 2D6 and UDP‐glucuronosyltransferase 1A1, respectively. P450 3A4‐ and 3A5‐ mediated thalidomide oxidation leads to a glutathione conjugate, which may be of relevance in the pharmacological and toxicological actions. Improved efficacy of carboplatin against malignant gliomas may be achieved by combination with hyperbaric oxygenation therapy. Recent findings on anticancer drug metabolism are summarized to understand information on the ADME of anticancer drugs.
Molecular Challenges in Front‐Loading Toxicity Testing of Anticancer Drugs in Drug Discovery
Authors: Johnson Dale E. , Sudarsanam Sucha 
Published: February 2012

AbstractDrug discovery of new anticancer therapeutics has shifted from a primary interest in cytotoxics to newer targeted therapies where specific molecular targets are the focus of both small‐molecule and biotherapeutic modalities. The practice of front‐loading toxicity testing has historically been used to accelerate programs; however, this must be tempered with the realization that many toxicities of targeted therapeutics relate to the actual mechanism of action for efficacy. Regulatory guidance is changing the requirements for toxicology testing for first‐in‐human clinical trials with the idea that translational assays may be discovered first in patients and these are then applied to longer‐term toxicology studies. Whether mechanistic assays can be directly linked to toxicity in nonclinical studies has yet to be fully elucidated, but it seems clear that early screening for chemical‐based toxicity will continue to be performed as part of the lead optimization process and that cardiotoxicity should be incorporated early on with targeted therapeutics because of the complex cross talk apparent in multiple signaling pathways.
Identification of Drug Metabolites
Authors: Obach Scott R. , Dalvie Deepak K. , Walker Gregory S. 
Published: February 2012

AbstractThe elucidation of chemical structures of drug metabolites is a key endeavor in the research on new drugs. The data can be useful both in the early drug design processes and later in the drug development process. In this chapter, the methods used to elucidate metabolite structures are described, including sample generation, sample processing procedures, mass spectrometry, and NMR spectroscopy.
Bioactivation I: Bioactivation by Cytochrome P450s
Authors: Dalvie Deepak K. 
Published: February 2012

AbstractMetabolism reactions generally result in detoxification of xenobiotics and are accompanied by the formation of chemically stable metabolites, which are devoid of pharmacological or toxicological activities. However, in some cases, these reactions can convert drugs to products that are either chemically reactive or pharmacologically active, a process that is commonly referred to asmetabolic activationorbioactivation. Most, if not all, functionalization and conjugation reactions can result in bioactivation. Even though all enzymes have the propensity to catalyze the metabolic activation of compounds, cytochrome P450 (P450) enzymes, which generally dominate metabolism, play a major role in the metabolic activation of drugs. The primary objective of this chapter is to provide an overview of bioactivation by P450 to pharmacologically active and chemically reactive metabolites. The common reactions that result in bioactivation of xenobiotics and consequences of bioactivation have been discussed here.
Clinical Implications ofCYPInduction‐Mediated Drug–Drug Interactions
Authors: Lin Jiunn H. , Guo Jianjun 
Published: February 2012

AbstractCytochrome P450 (CYP) induction‐mediated drug interaction is a major concern in clinical practice. Although the reported cases of CYP induction‐mediated drug interactions are less frequent than that of CYP inhibition‐mediated drug interactions, there are two major concerns with CYP induction. First, induction may cause a reduction in therapeutic efficacy as a result of increased drug metabolism. Second, induction may create an undesirable imbalance between bioactivation and detoxification as a result of increased formation of reactive metabolites leading to an increase in the risk of metabolite‐induced toxicity. Therefore, CYP induction has been considered as an important factor for consideration during drug discovery and development. The purpose of this chapter is to review the effects of CYP induction on pharmacokinetics of drugs and its clinical implications.
Matrix‐Assisted Laser Desorption/Ionization
Authors: Limbach Patrick A. , Hossain Mahmud 
Published: February 2012

AbstractMatrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) is an enabling approach for the characterization of biomolecules, synthetic polymers, petroleum products, and various other inorganic and organic materials. Its popularity can be attributed to the discovery that the addition of a light‐absorbing compound (the matrix) to the sample solution enables the desorption and ionization, without attendant fragmentation, of traditionally labile compounds. This chapter begins with a historical development of the technique. Next, the variety of matrix options that exist in MALDI, including suspension matrices, ionic matrices (room temperature ionic liquids, RTILs), carbon nanotubes (with/without functionalization), combined detergent/MALDI matrices (to solubilize hydrophobic analytes and enhance signal), and the most popular and successful chemical matrices along are discussed. MALDI instrumentation and analytical methods are presented, with a particular focus on how MALDI‐MS can be used to obtain molar mass and structural information from various classes of biomolecules. Finally, the chapter concludes by examining several applications of interest in the pharmaceutical field, such as bacterial genotyping, high throughput screening of small molecules, and characterization of drug delivery vehicles. While MALDI‐MS has not been a traditional “first‐choice” for pharmaceutical research because of the widespread utilization of liquid chromatography‐based mass spectrometry (LC‐MS) methods, there are several areas where MALDI‐MS provides clear and compelling advantages in pharmaceutical research.
Nuclear Magnetic Resonance Spectroscopy for the Study of Drug Metabolism
Authors: Reily Michael D. , Huang Stella , Caceres‐Cortes Janet , Johnson Kim , Shu Yue‐Zhong 
Published: February 2012

AbstractThis chapter provides an overview of the specific structural information that nuclear magentic resonance (NMR) spectroscopy can provide in drug metabolites in solution, such as sites of modification at the atomic level, regio‐ and stereo isomer characterization, and dynamic physical properties, and how these parameters are measured. Throughout, the complementarity of NMR‐derived information with that provided by other analytical methods, particularly LC‐MS, is highlighted. Limitations and costs associated with NMR are discussed in some detail as are considerations for the ideal NMR equipment need to conduct drug metabolism studies. This includes a discussion of hyphenated methods such as LC‐NMR. NMR is nonselective, and hence, the importance of sample preparation for NMR is highlighted and described. The somewhat different approaches required in discovery and development applications are discussed and are illustrated through many examples in separate sections, and finally, a brief discussion of stereochemical measurement by NMR is provided.
High Throughput Quantitative Mass Spectrometry
Authors: Williams Jon D. , Grant Russell 
Published: February 2012

AbstractSince the advent of atmospheric pressure ionization sources, liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) has become the indisputable gold standard technique for quantitative analysis forin vitroandin vivobiological samples. Dramatic improvements in throughput by LC‐MS/MS have been achieved based on need and confluences of technologies over the past 20 years primarily in mass spectrometry (MS) and liquid chromatography (LC) augmented with improvements in automation and robotics. Evolutions in mass spectrometer sampling interfaces, mass analyzers, ion optics, and electronics have enabled the development of a rugged, reliable, and exquisitely sensitive platform. Instrument‐to‐instrument variation now is controlled such that instrument parameters can be translated in a facile manner to like platforms from the same manufacturer. Continued increases in MS instrument sensitivity have enabled reductions in sample loading needs, a key requirement for robust, hands‐free operation. Instrument tuning algorithms and sample delivery workflows have been developed to automatically create acquisition methods for chosen analytes to enable streamlining of method development and sample analysis. Systematic evolutions in LC pumps and column hardware have led to better sensitivity, improved chromatographic resolution with a concomitant reduction in analysis time, and robustness. Numerous techniques that rely on robust chromatography have been developed to increase the effective data collection rate of mass spectrometers, the time spent acquiring data of value. In a single decade, we have seen evolution from the serial delivery mode of a single LC system coupled to a mass spectrometer up to commercial versions of eight‐channel “true” parallel and eight‐channel serial (staggered) parallel LC systems coupled to a single mass spectrometer. Before sample analysis, generic automated sample preparation techniques have been developed. Robotics capabilities have improved sample handling processes for protein and phospholipid removal along with sample pooling, through the use of 96‐ and 384‐well‐plate‐based systems. Postacquisition data processing and reporting solutions have also been developed to handle the greater influx of data generated by this high throughput platform. When these developments are taken into account, we are left with the realization that quantitative MS has become an industrialized process. We now have dramatically shortened the timelines required for analytical support to the point it is not a rate‐limiting step in the discovery process. This chapter discusses the evolution of high throughput LC‐MS/MS and many of the approaches that have been pursued in the past decade. We also consider non‐LC‐based workflows that utilize alternative ionization sources. With some of these new strategies, it is conceivable that data acquisition rates will reach or exceed multiple assays per second.
Metabolism‐Based Consequences of Polytherapy with Antiepileptic Drugs
Authors: Patsalos Philip N. 
Published: February 2012

AbstractCombination antiepileptic drug (AED) therapy (the use of two or more drugs) is common in patients with active epilepsy. Additionally, many patients will require concurrent treatment with other agents for the management of concomitant or intercurrent conditions. Consequently, clinically important interactions may occur not only between AEDs but also between AEDs and non‐AED drugs. Interactions involving induction or inhibition of hepatic metabolism involving cytochrome P450 isoenzymes and uridine glucuronyl trasferases are common. Carbamazepine, phenobarbital, phenytoin, and primidone induce metabolism, leading to decreased plasma levels and reduced pharmacological effects of AEDs such as lamotrigine, tiagabine, topiramate, and valproic acid. In contrast, the AEDs gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, tiagabine, topiramate, vigabatrin, and zonisamide do not induce the metabolism of other AEDs. Inhibitory interactions, with concurrent increase in plasma levels, include those with valproic acid (lamotrigine and phenobarbital), felbamate (clobazam, phenytoin, valproic acid), and stiripentol (carbamazepine, clobazam phenytoin, phenobarbital primidone, and valproic acid). With regard to interactions with non‐AED drugs, carbamazepine, phenobarbital, phenytoin, and primidone can decrease the plasma levels of many antineoplastic, antimicrobial, cardiovascular, immunosuppressant, and psychotropic agents, as well as oral contraceptive steroids. The converse can also occur; for example, certain macrolide antibiotics, antifungals, diltiazem, isoniazid, and verapamil can inhibit carbamazepine metabolism, while lamotrigine metabolism is induced by oral contraceptive steroids. The AEDs with the lowest propensity to interact at the level of hepatic metabolism are gabapentin, lacosamide, levetiracetam, pregabalin, and vigabatrin. AED interactions are best managed by careful monitoring of clinical response and of measurement of plasma drug levels whenever an interacting drug is added or removed from a patient's AED regimen and by undertaking and dosage adjustments as necessary.
Identification of Novel DNA‐Binding Proteins Using DNA‐Affinity Chromatography/Pull Down
Authors: Jutras Brandon L. , Verma Ashutosh , Stevenson Brian 
Published: February 2012

AbstractThis units presents methods through which one may isolate and identify novel bacterial DNA‐binding proteins. Briefly, the DNA sequence of interest is affixed to beads, and then incubated with bacterial cytoplasmic extract. Washes with buffers containing nonspecific DNA and low‐salt concentrations will remove non‐adhering and low‐specificity DNA‐binding proteins, while subsequent washes with higher salt concentrations will elute more specific DNA‐binding proteins. Eluted proteins may then be identified by standard proteomic techniques. Curr. Protoc. Microbiol. 24:1F.1.1‐1F.1.13. © 2012 by John Wiley & Sons, Inc.
AZ91D/TiB2 Nanocomposites Fabricated by Solidification Nanoprocessing
Authors: Choi Hongseok , Sun Yi , Slater Ben P. , Konishi Hiromi , Li Xiaochun 
Published: February 2012

AbstractAZ91D, as one of the most widely used casting magnesium alloys, still suffers from inadequate mechanical performances for various applications. Nanoparticles could be used to form high‐performance magnesium matrix nanocomposites. Among all nanoparticles, TiB2 has great potentials to enhance the mechanical property of AZ91D. This paper studies the microstructures and mechanical property of AZ91D‐TiB2 nanocomposites fabricated through solidification nanoprocessing. TiB2 nanoparticles with a diameter of 25 nm are effectively fed into the AZ91D melt through a newly developed automatic nanoparticle‐feeding system. Ultrasonic cavitation is used to disperse these nanoparticles in AZ91D melt for casting. With 2.7 wt% (about 1.0 vol%) of TiB2 nanoparticles addition, the mechanical property of AZ91D is much enhanced (by 21, 16, and 48% for yield strength, tensile strength, and ductility, respectively). Microstructural analysis with optical microscope, SEM, and S/TEM show that α‐Mg grain and a network of massive brittle intermetallic phase (β‐Mg17Al12) are simultaneously refined and modified. Further study suggests that the enhancement of mechanical properties of AZ91D is attributed not only to primary phase grain refinement, but also to the modification of intermetallic β‐Mg17Al12 by TiB2 nanoparticles.