bluuebunny/crossref_metadata_2025 huggingface dataset:
Les modalités d'interprétation des récits bibliques de guérison aujourd'hui
Authors: Boureux Christophe
Published: February 2012

Résumé Le type d’interprétation des textes bibliques que les prédicateurs des séances de guérison mettent en œuvre est plutôt archaïsant que fondamentaliste au sens strict. Il vise à présenter une forme de vie antimoderne centrée sur la guérison comme évaluation forte de l’existence. Son opérateur symbolique est la voix du prédicateur.
Pouvoir de guérir et théologie des ministères, charisme et institution
Authors: Lehmkühler Karsten
Published: February 2012

Résumé Après une réflexion introductive sur l’articulation entre l’« institution » et le « charisme », l’auteur présente des textes clé des Églises catholique, anglicane et protestantes, concernant chaque fois les questions de la guérison : l’ Instruction sur les prières pour obtenir de Dieu la guérison (2000) de la Congrégation pour la doctrine de la foi, la grande étude A Time to Heal (2000), élaborée pour le House of Bishops de la Church of England , et deux textes plus locaux provenant des Églises protestantes en Alsace et en Lorraine, ainsi que des Églises protestantes de Bâle (Suisse). L’analyse de ces textes s’intéresse aussi bien aux fondements doctrinaux qu’aux recommandations concrètes par rapport à une pratique de guérison au sein des Églises mentionnées. Une conclusion souligne les aspects positifs des réflexions ecclésiales en la matière et propose, en même temps, une liste de desiderata en vue d’une meilleure compréhension et « régulation » de ces pratiques dans l’avenir.
La diffusion des péjorations communautaires après 1945
Authors: Lebourg Nicolas
Published: February 2012

Résumé Ce que l’on peut dénommer « altérophobie » est le versant négatif du sentiment d’appartenance communautaire. L’extrême-droite occupe, depuis la fin du xix e siècle, le terrain du nationalisme politique, à la française ou à l’allemande. Aujourd’hui, ce qui se joue autour de l’islamophobie correspond à la plus récente dépréciation « altérophobique ». L’emploi de ce terme n’est pas à rejeter systématiquement, à moins de supprimer aussi racisme, antisémitisme, etc. En France, la préférence nationale devient une thématique qui ab initio ne concernait guère néo-fascistes et néo-nazis, en raison d’une sympathie marquée pour les mondes arabo-musulmans. La naissance du Front national a joué un rôle important dans cet infléchissement. Le conflit israélo-palestinien a fait croître deux altérophobies exclusives l’une de l’autre. Le débat médiatique n’a pas permis d’ajuster ou d’affiner les concepts. Le discours antitotalitaire a tenté de rationaliser les débats avec plus ou moins de succès. La défense irréfléchie des sociétés ouvertes augure mal d’une nouvelle ère de sociétés fermées.
Preparing for the Future: What Nurses Need to Know
Authors: White Maureen T.
Published: February 2012

This column outlines some of the challenges and opportunities for nurses in the coming years. Implications for nursing practice and education are highlighted.
Psychiatric Nursing Emergency: A Simulated Experience of a Wrist-Cutting Suicide Attempt
Authors: Lilly Mary L. , Hermanns Melinda S. , Crawley Bill
Published: February 2012

A simulated wrist-cutting suicide attempt scenario was developed and implemented, with the goal of integrating the concepts of psychiatric emergency care, contraband, environmental assessment, and personal safety. Faculty also wanted to convey and provide care and support for participants throughout the visually and emotionally stimulating activity. The underlying premise was that providing readings and lecture material on these topics was insufficient to the level of learning and performance needed by nursing students and novice nurses. However, actual student clinical episodes integrating these concepts were also infrequent, unpredictable, and often not conducive to student learning. Therefore, faculty implemented a simulation teaching modality to deliver the concepts in a vivid and memorable format. A standardized rating scale on perceived learning and care from faculty during the course of the simulation was administered immediately following participation in the activity. Participants were overwhelmingly positive in their assessment of the activity, reporting an enhanced appreciation for safety in the conduct of inpatient psychiatric nursing care. Further, the faculty member’s observation and post-simulation processing of the activity noted cognitive, behavioral, and emotional responses at the individual and group levels related to communication, observation and assessment, decision making, and interpersonal support.
Bath Salts: They Are Not What You Think
Authors: Wieland Diane M. , Halter Margaret J. , Levine Ciara
Published: February 2012

Psychoactive bath salts are a relatively new group of designer drugs sold as tablets, capsules, or powder and purchased in places such as tobacco and convenience stores, gas stations, head shops, and the Internet. Bath salts are stimulant agents that mimic cocaine, lysergic acid diethylamide, methamphetamine, or methylenedioxymethamphetamine (ecstasy). The most common bath salts are the cathinone derivatives 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxy-N-methylcathinone (methylone). The drugs cause intense stimulation, euphoria, elevated mood, and a pleasurable “rush.” Tachycardia, hypertension, peripheral constriction, chest pain, hallucinations, paranoia, erratic behavior, inattention, lack of memory of substance use, and psychosis have been observed in those who have used bath salts. The U.S. Drug Enforcement Administration recently exercised an emergency authority to name three key ingredients in bath salts as Schedule I, thereby making them illegal to possess or sell in the United States. Nursing implications related to both clinical and educational settings are discussed.
Intraocular Femtosecond Laser Use in Traumatic Cataracts Following Penetrating and Blunt Trauma
Authors: Nagy Zoltán Zsolt , Kránitz Kinga , Takacs Agnes , Filkorn Tamás , Gergely Róbert , Knorz Michael C.
Published: February 2012

PURPOSE:

To investigate the use of femtosecond laser cataract surgery in traumatic cataracts of different origin.

METHODS:

The first case developed acute traumatic cataract due to penetrating injury of the cornea and the anterior lens capsule; the second developed traumatic cataract 11 years after a penetrating corneal injury; and the third developed a “white” cataract 12 months after blunt ocular trauma. In all cases, 4.5-mm capsulorrhexis and corneal incisions were performed using a femtosecond laser system (Alcon LenSx Inc), and nucleus liquefaction with the laser was performed additionally in the second case.

RESULTS:

In all patients, a capsulorrhexis could be created with the femtosecond laser. Preexisting radial tears were present in the first case, but the remaining anterior capsule could be cut with the laser. The second and third cases showed an intact 4.5-mm capsulorrhexis. Corneal incisions were stable in all cases, and nucleus liquefaction was possible in the second case (grade 1–2 nuclear density).

CONCLUSIONS:

Results indicate that a femtosecond laser can be used successfully in certain instances of traumatic cataract after penetrating eye injury, even if an anterior capsule laceration is present, and also after blunt trauma resulting in “white” cataracts.
China’s Internet lexicon: Symbolic meaning and commoditization of Grass Mud Horse in the harmonious society
Authors: Wang Shaojung Sharon
Published: February 2012

There is a long history of the Chinese concept of Internet regulation, which emphasizes stability and unity for a harmonious society and strong technical control. “Grass Mud Horse” (草泥马), a vulgar expression similar to an obscene curse word, has, since early 2009, been used by the country’s Internet users as a political parody in response to their government’s campaign of building a harmonious socialist society. “Grass Mud Horse” has later been fashioned into the name of a storybook character, and has spawned music videos and faux documentaries. Its themed merchandise, such as plush toys, is being sold over the Internet. This study sets out to examine the transformation of “Grass Mud Horse” into the mass production of cultural goods created and disseminated through the Internet. It argues that the exchange values of “Grass Mud Horse” represent the equivalent relation between commodities, symbols, and popular culture. While “Grass Mud Horse” has been commoditized by the increasing usage of popular culture; this is also the system of mass production and the homogenizing regime of capital, which produces mass desires, tastes, and behavior rather than valid social movements.
A Descriptive Study of Cooperating Teachers’ Perceptions Regarding Student Teacher Preparation
Authors: MacLeod Rebecca B. , Walter Jennifer S.
Published: February 2012

The purpose of this study was to investigate the perceptions of cooperating teachers regarding the level of preparedness of specific student teachers at the beginning of the student-teaching experience. Fifty-three secondary ensemble teachers (orchestra, band, and choir) completed a survey rating how prepared their most recent student teacher was in the areas of personal skills, teaching skills, and musical skills and provided feedback regarding the skill that needed the most attention from the university to improve music teacher preparation. Cooperating teachers rated student teachers similarly in all three categories. Differences were found between orchestra, band, and choir teachers relative to the skill that was selected in each category as needing the most attention. Orchestra and band teachers selected effective rehearsal pace, knowledge of subject matter, and secondary instrument skills as needing additional focus from university programs, while choral teachers selected piano skills and teaching and learning strategies as important areas to develop. Additional trends were noted between orchestra, band, and choral teachers and implications for music teacher education were discussed.
Reconstruction of a Total Soft Palatal Defect Using a Folded Radial Forearm Free Flap and Palmaris Longus Tendon Sling
Authors: Lee Myung Chul , Lee Dong Won , Rah Dong Kyun , Lee Won Jai
Published: February 2012

Background The soft palate functions as a valve and helps generate the oral pressure required for normal speech resonance. Speech problems and nasal regurgitation can result from a soft palatal defect. Reduction of the size of the velopharyngeal orifice is required to compensate for the lack of mobility in a reconstructed soft palate. We suggest a large volume folded free flap for reduction of the caliber and a palmaris longus tendon sling for suspension of the reconstructed palate.

Methods Six patients had total soft palate resection for tonsillar cancer and reconstruction with a large volume folded radial forearm free flap combined with a palmaris longus sling. A single surgeon and speech therapist examined the patients with three standardized speech assessment tools: nasometer test, consonant articulation test, and speech acuity test performed for speech evaluation.

Results Mean nasalance score was 76.20% for sentences with nasal sounds and 43.60% for sentences with oral sounds. Hypernasality was seen for oral sound sentences. The mean score of the picture consonant articulation test was 84% (range, 63% to 100%). The mean score of the speech acuity test was 5.84 (range, 5 to 6). These mean ratings represent a satisfactory level of speech function.

Conclusions The large volume folded free flap with a palmaris longus tendon sling for total soft palate reconstruction resulted in satisfactory prognosis for speech despite moderate hypernasality.
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.
Case Reports of Adipose-derived Stem Cell Therapy for Nasal Skin Necrosis after Filler Injection
Authors: Sung Ha Min , Suh In Suck , Lee Hoon-Bum , Tak Kyoung Seok , Moon Kyung Min , Jung Min Su
Published: February 2012

With the gradual increase of cases using fillers, cases of patients treated by non-medical professionals or inexperienced physicians resulting in complications are also increasing. We herein report 2 patients who experienced acute complications after receiving filler injections and were successfully treated with adipose-derived stem cell (ADSCs) therapy. Case 1 was a 23-year-old female patient who received a filler (Restylane) injection in her forehead, glabella, and nose by a non-medical professional. The day after her injection, inflammation was observed with a 3×3 cm skin necrosis. Case 2 was a 30-year-old woman who received a filler injection of hyaluronic acid gel (Juvederm) on her nasal dorsum and tip at a private clinic. She developed erythema and swelling in the filler-injected area A solution containing ADSCs harvested from each patient's abdominal subcutaneous tissue was injected into the lesion at the subcutaneous and dermis levels. The wounds healed without additional treatment. With continuous follow-up, both patients experienced only fine linear scars 6 months postoperatively. By using adipose-derived stem cells, we successfully treated the acute complications of skin necrosis after the filler injection, resulting in much less scarring, and more satisfactory results were achieved not only in wound healing, but also in esthetics.
A Case Report of Sweet's Syndrome with Parotitis
Authors: Jo Myoung Soo , Lim Young Bin , Shin Hea Kyeong , Choe Joon , Seul Jung Hyun , Jang Tae Jung
Published: February 2012

Sweet's syndrome is characterized by clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions, and a diffuse infiltrate of mature neutrophils. This is a report of our experience of Sweet's syndrome with parotitis. A 57-year-old man initially presented with tender swelling on the right cheek similar to parotitis. His symptoms relapsed despite the use of an oral antibiotic agent for 3 weeks. He additionally presented with erythematous papules and plaques on the periocular area and dorsum of both hands. Histiopathologic findings on punch biopsy of the right dorsum of the hand showed superficial perivenular histiocytic infiltration without vasculitis. We confirmed this as histiocytoid Sweet's syndrome and used systemic corticosteroid. After initiation of treatment with systemic corticosteroids, there was a prompt recovery from both the dermatosis-releated symptoms and skin lesions. Sweet's syndrome should be considered in patients with therapy-refractory parotitis and unclear infiltrated nodules. We present a confusing case who initially appeared to have parotitis but turned out to have histiocytoid Sweet's syndrome.
Vein Wrapping Technique for Nerve Reconstruction in Patients with Thyroid Cancer Invading the Recurrent Laryngeal Nerve
Authors: Yoo Young Moon , Lee Il Jae , Lim Hyoseob , Kim Joo Hyoung , Park Myong Chul
Published: February 2012

Recurrent laryngeal nerve paralysis is the most common and serious complication after thyroid cancer surgery. The objective of this study was to report the advantages of the vein wrapping technique for nerve reconstruction in patients with thyroid cancer invading the recurrent laryngeal nerve and its effects on postoperative phonatory function. The subjects were three patients who underwent resection of the recurrent laryngeal nerve during surgical extirpation of papillary thyroid cancer. Free ansa cervicalis nerve graft or direct neurorrhaphy with a vein wrapping technique was used to facilitate nerve regeneration, protect the anastomosed nerve site mechanically, and prevent neuroma formation. One-year postoperative laryngoscopic examination revealed good vocal cord mobility. Maximum phonation time (19.5 ± 0.3 sec) was longer than a previously-reported value in conventional reconstruction patients (18.8 ± 6.6 sec). The present phonation efficiency index (7.88 ± 0.78) was higher than that previously calculated in conventional reconstruction (7.59 ± 2.82). The mean value of the Voice Handicap Index-10 was 6, which was within the normal range. This study demonstrates improvement in phonation indices measured 1 year after recurrent laryngeal nerve reconstruction. Our results confirm that the vein wrapping technique has theoretical advantages and could be favored over conventional reconstruction techniques for invenerate nerve injuries.
Mouse Models of Atherosclerosis
Authors: Maganto‐Garcia E. , Tarrio M. , Lichtman A.H.
Published: February 2012

Genetically 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

Intestinal 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

From 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

The 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

Polymorphic 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

Drug 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

The 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

Metabolism 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

Cytochrome 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

Matrix‐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

This 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

Since 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

Combination 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

This 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

AZ91D, 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.
Sorting Stable versus Unstable Hypothetical Compounds: The Case of Multi‐Functional ABX Half‐Heusler Filled Tetrahedral Structures
Authors: Zhang Xiuwen , Yu Liping , Zakutayev Andriy , Zunger Alex
Published: February 2012

Electronic structure theory has recently been used to propose hypothetical compounds in presumed crystal structures, seeking new useful functional materials. In some cases, such hypothetical materials are metastable, albeit with technologically useful long lifetimes. Yet, in other cases, suggested hypothetical compounds may be significantly higher in energy than their lowest‐energy crystal structures or competing phases, making their synthesis and eventual device‐stability questionable. By way of example, the focus here is on the family of 1:1:1 compounds ABX called “filled tetrahedral structure” (sometimes called Half‐Heusler) in the four groups with octet electron count: I‐I‐VI (e.g., CuAgSe), I‐II‐V (e.g., AgMgAs), I‐III‐IV (e.g., LiAlSi), and II‐II‐IV (e.g., CaZnSn). First‐principles thermodynamics is used to sort the lowest‐energy structure and the thermodynamic stability of the 488 unreported hypothetical ABX compounds, many of which were previously proposed to be useful technologically. It is found that as many as 235 of the 488 are unstable with respect to decomposition (hence, are unlikely to be viable technologically), whereas other 235 of the unreported compounds are predicted to be thermodynamically stable (hence, potentially interesting new materials). 18 additional materials are too close to determine. The electronic structures of these predicted stable compounds are evaluated, seeking potential new material functionalities.
Functional Silk: Colored and Luminescent
Authors: Tansil Natalia C. , Koh Leng Duei , Han Ming‐Yong
Published: February 2012

Silkworm silk is among the most widely used natural fibers for textile and biomedical applications due to its extraordinary mechanical properties and superior biocompatibility. A number of physical and chemical processes have also been developed to reconstruct silk into various forms or to artificially produce silk‐like materials. In addition to the direct use and the delicate replication of silk's natural structure and properties, there is a growing interest to introduce more new functionalities into silk while maintaining its advantageous intrinsic properties. In this review we assess various methods and their merits to produce functional silk, specifically those with color and luminescence, through post‐processing steps as well as biological approaches. There is a highlight on intrinsically colored and luminescent silk produced directly from silkworms for a wide range of applications, and a discussion on the suitable molecular properties for being incorporated effectively into silk while it is being produced in the silk gland. With these understanding, a new generation of silk containing various functional materials (e.g., drugs, antibiotics and stimuli‐sensitive dyes) would be produced for novel applications such as cancer therapy with controlled release feature, wound dressing with monitoring/sensing feature, tissue engineering scaffolds with antibacterial, anticoagulant or anti‐inflammatory feature, and many others.
Implications for genotype–phenotype predictions in Townes–Brocks syndrome: Case report of a novel SALL1 deletion and review of the literature
Authors: Miller Erin M. , Hopkin Robert , Bao Liming , Ware Stephanie M.
Published: February 2012

Townes–Brocks syndrome (TBS) is a well‐described genetic syndrome characterized by anal, ear, and thumb anomalies and variable expressivity. Over 60 nonsense and frameshift mutations have been identified in SALL1, the zinc finger transcription factor causing TBS, and are proposed to cause disease via a dominant negative mechanism. In contrast, only four deletions have been described, with mild phenotypes reported as a result of haploinsufficiency. We report on a family with features of TBS in whom a novel 149 kb deletion spanning the SALL1 gene was identified by high resolution cytogenetics SNP microarray. We review the available genotype–phenotype information for all known truncating mutations and deletions. Taken together, they do not support the correlation of SALL1 deletions with a milder TBS phenotype and highlight a need for more robust clinical phenotyping combined with investigation of mutational mechanism. © 2012 Wiley Periodicals, Inc.
Adams–Oliver syndrome and portal hypertension: Fortuitous association or common mechanism?
Authors: Silva Gisela , Braga Alexandre , Leitão Banquart , Mesquita Abel , Reis Aurélio , Duarte Carlos , Barbot José , Silva Ermelinda Santos
Published: February 2012

Adams–Oliver syndrome (AOS) is a rare condition defined by combination of cutis aplasia and transverse limb abnormalities. Some authors have described a possible association between this syndrome and portal hypertension (PH) due to hepatoportal sclerosis (HPS). We present a boy with AOS who developed a progressive splenomegaly and hypersplenism at the age of 2 months, and was admitted for acute gastrointestinal bleeding (GI) at the age of 9 months. Subsequently, we documented an extrahepatic portal vein obstruction and esophageal varices. After several episodes of cataclysmic upper GI bleeding a mesentero‐portal shunt (MPS) was performed at 10 months. The shunt thrombosed, and after three failed attempts of thrombectomy, it was removed. One month later a splenorenal shunt was performed, and this closed spontaneously by 3 years. The patient suffered from ischemic stroke after placing the first shunt, and has spastic diplegia, left frontal lobe epilepsy, hyperactivity and attention deficit disorder, and severe psychomotor delay. At 11 years and he presented with chronic liver failure and hyperammonemia and coagulopathy. We hypothesize that there may be an early embryonic vascular abnormality (vascular disruption) that may explain these vascular phenomena. © 2012 Wiley Periodicals, Inc.
Array CGH on unstimulated blood does not detect all cases of Pallister–Killian syndrome: A skin biopsy should remain the diagnostic gold standard
Authors: Hodge Jennelle C. , Hulshizer Rachael L. , Seger Pam , St Antoine Angelique , Bair Jennifer , Kirmani Salman
Published: February 2012

A child whose features are consistent with Pallister–Killian syndrome (PKS) did not have detectable tetrasomy 12p due to an additional isochromosome 12p in an unstimulated blood specimen by interphase FISH or array CGH analysis. The diagnosis of PKS was made through these methods solely in a skin biopsy specimen. To determine the sensitivity of our array CGH platform to tetrasomy 12p mosaicism, dilutions of DNA from both the child's skin fibroblasts and a PKS cell line were analyzed. Tetrasomy 12p at 10% mosaicism was identifiable but 5% was below the limit of detection. This result suggests through extrapolation that the tetrasomy 12p is present in <10% of cells in our patient's blood, confirming the tissue‐limited mosaicism of PKS. Multiple recent studies show that array CGH provides greater sensitivity than chromosome analysis to detect mosaic abnormalities including that of tetrasomy 12p in blood specimens. However, our case demonstrates that the biology of PKS precludes the exclusive use of array CGH on blood for diagnosis. A tissue sample should continue to be the diagnostic gold standard for PKS. © 2012 Wiley Periodicals, Inc.