bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of genes coding for CD46, CD55, and C4b‐binding protein in patients with idiopathic, recurrent, spontaneous pregnancy loss
Authors: Mohlin Frida C. , Mercier Eric , Fremeaux‐Bacchi Veronique , Liszewski M. Kathryn , Atkinson John P. , Gris Jean‐Christophe , Blom Anna M.
Published: March 2013

Since a tightly regulated complement system is needed for a successful pregnancy, we hypothesized that alterations in complement inhibitors may be associated with idiopathic, recurrent miscarriage. We sequenced all exons coding for three complement inhibitors: C4b‐binding protein (C4BP), CD46, and CD55 in 384 childless women with at least two miscarriages that could not be explained by known risk factors. Several alterations were found in C4BPA, of which the R120H, I126T, and the G423T mutations affected the expression level and/or the ability of recombinant C4BP to serve as cofactor for factor I. The only variant in C4BPB was located in the C‐terminal part, and did not impair the polymerization of the molecule. Our results identify for the first time alterations in C4BP in women experiencing recurrent miscarriages. We also found four CD46 alterations in individual patients that were not found in healthy controls. One of the rare variants, P324L, showed decreased expression, whereas N213I resulted in deficient protein processing as well as an impaired cofactor activity in the degradation of both C4b and C3b. The identified alterations may result in in vivo consequences and contribute to the disorder but the degree of association must be evaluated in larger cohorts.
Nickel Nanoparticles as Racemization Catalysts for Primary Amines
Authors: Geukens Inge , Plessers Eva , Seo Jin Won , De Vos Dirk E.
Published: March 2013

By combining bases that are known to racemize benzylic amines with a nickel(II) salt, active nickel nanoparticles were obtained that can be used as catalysts in the racemization of both aliphatic and benzylic primary amines. The nanoparticles are stable in the ionic liquid tetrabutylammonium bromide and can complete most racemizations within a few hours with excellent selectivity. The problem of the incompatibility of the strongly reducing racemization catalyst and the enzymatic amine resolution catalyst was overcome by using a two‐pot system with a biphasic racemization step. Consecutive contact of a nonane layer that contained the amine with the acylating enzyme and with the racemizing Ni nanoparticles in the ionic liquid allowed the 50 % amide yield limit of a kinetic resolution to be successfully surpassed.
Aromatic Claisen Rearrangements of O‐Prenylated Tyrosine and Model Prenyl Aryl Ethers: Computational Study of the Role of Water on Acceleration of Claisen Rearrangements
Authors: Osuna Sílvia , Kim Seonah , Bollot Guillaume , Houk Kendall N.
Published: March 2013

LynF, an enzyme from the TruF family, O‐prenylates tyrosines in proteins; subsequent Claisen rearrangements give C‐prenylated tyrosine products. These reactions in tyrosines and model phenolic systems have been explored with DFT and SCS‐MP2 calculations. Various ab initio benchmarks have been used (CBS‐QB3, MP2, SCS‐MP2) to examine the accuracy of commonly used density functionals, such as B3LYP and M06‐2X. Solvent effects from water were considered by using implicit and explicit models. Studies of the ortho‐C‐prenylation and Claisen rearrangement of tyrosine, and the Claisen rearrangement of α,α‐dimethylallyl (prenyl) coumaryl ether establish the energetics of these reactions both in the gas phase and in aqueous solution.
Detection of the antibacterial effect of essential oils on outer membrane proteins of Pseudomonas aeruginosa by lab‐on‐a‐chip and MALDI‐TOF/MS
Authors: Felső Péter , Horváth Györgyi , Bencsik Tímea , Godányi Roland , Lemberkovics Éva , Böszörményi Andrea , Böddi Katalin , Takátsy Anikó , Molnár Péter , Kocsis Béla
Published: March 2013

In bacteria, structural changes of outer membrane protein (OMP) composition may have an effect on the adhesive ability and pathogenic properties of the organisms. Pseudomonas aeruginosa can develop an intrinsic resistance to a wide range of biocides, which is associated with the nature of its outer membrane. The aim of our study was to examine how the essential oils of cinnamon bark and clove modify the OMP composition of the human pathogen P. aeruginosa strains and to identify the structure of proteins that are considerably changed after incubation with essential oils. Chemical composition of the oils was analysed by using gas chromatography and gas chromatography–mass spectrometry. Eugenol (83.7%) was the main component of the clove oil, while trans‐cinnamic aldehyde (73.2%) was the main constituent in cinnamon bark oil. Values for the minimum inhibitory concentration (MIC) of the oils were determined by a modified tube dilution method. The oils were administered to the culture at concentrations of 0.5 × MIC and 2 × MIC and incubated for 60 min. After OMP preparation, the structure of proteins was analysed by MALDI‐TOF/MS. Cinnamon and clove oil could influence the OMP composition of Pseudomonas strains. Proteins with molecular weights of 42.7 kDa and 79.4 kDa disappeared after treatment with cinnamon and clove oil, respectively. Quantitative changes in the protein profile may contribute to the explanation of the antibacterial effect of cinnamon bark and clove essential oils on pathogenic Pseudomonas strains. Copyright © 2013 John Wiley & Sons, Ltd.
Comparison of non‐reflective boundary conditions for a free‐rising turbulent axisymmetric plume
Authors: Hattori T. , Norris S.E. , Kirkpatrick M.P. , Armfield S.W.
Published: March 2013

The stability and accuracy of radiation type non‐reflective outflow boundary conditions, as well as the standard Neumann boundary condition with zero normal derivative, have been compared for the numerical simulation of a turbulent axisymmetric plume with Reynolds number of 7700 and Prandtl number of 0.71. Comparison of the performance of the boundary conditions with respect to each other, and to the results obtained for an extended domain, shows that a one‐dimensional scheme in which advection and diffusion terms are included in the radiation equation is the optimum approach for the plume simulation. Copyright © 2013 John Wiley & Sons, Ltd.
Exercise to Lose Money? Irrational Exercise Behavior from the Chinese Warrants Market
Authors: Liao Li , Li Zhisheng , Zhang Weiqiang , Zhu Ning
Published: March 2013

Using a market‐level exercise data set and an individual‐level trading data set between August 2006 and June 2009, this study examines the incidence of two types of irrational exercise behavior in the Chinese warrants market. We find that 121.64 million shares of warrants (0.64% of all warrants) were either exercised with an immediate loss or failed to be exercised, resulting in foregone risk‐free profits. These irrational exercises caused warrant holders to lose over 717.79 million Yuan. Some of the irrational behavior can be attributed to “entertainment seeking” and the “T + 1” rule practiced in the Chinese security market, but the majority is attributed to warrant holders' ignorance and/or negligence of warrant mechanics. Our findings provide additional field evidence of clearly irrational exercise behavior in a derivatives market. We also find that investor education, information and guidance provision can mitigate the incidence of irrational exercise behavior significantly. © 2013 Wiley Periodicals, Inc. Jrl Fut Mark 34:399–419, 2014
Shale Gas—Community Relations: NIMBY or Not? Integrating Social Factors Into Shale Gas Community Engagements
Authors: Cotton Matthew
Published: March 2013

Shale gas extraction is an issue of significant local and national political controversy. It is widely recognized that engaging the public with both the science of fracking and with local siting processes is important in achieving public acceptance.
Legislation—Dodd‐Frank: You Might Be a Swap Dealer if…
Authors: Prokop Michael
Published: March 2013

While the title of this article may sound a bit like the beginning of a Jeff Foxworthy comedy routine, it is very much the way many firms that are trading in the energy markets feel today. Continued regulatory uncertainty, delays in regulatory rule implementations, and the changing face of the market have most market participants cautiously moving forward with the daily trading requirements as they exist now.
The stability of an evolving Atlantic meridional overturning circulation
Authors: Liu Wei , Liu Zhengyu , Hu Aixue
Published: March 2013

In this study, we propose a generalized stability indicator, L, for a slowly evolving and quasi‐steady Atlantic meridional overturning circulation (AMOC), which represents a feedback related to the AMOC and its associated freshwater transport within the Atlantic basin. As an improvement from previous indicators for the AMOC in equilibrium, this generalized indicator does not require a divergence‐free freshwater transport in the Atlantic for a collapsed AMOC, which enables it to correctly monitor the AMOC stability through the AMOC hysteresis loop in the coupled atmosphere‐ocean general circulation models. From the simulation, the indicator L suggests that the AMOC is in a stable regime, with single equilibrium under the present‐day and the Last Glacial Maximum (LGM) climates. However, under the present‐day climate, a Bering Strait (BS) closure will diminish the freshwater outflow from the North Atlantic into the Arctic as the AMOC collapses, resulting in a freshwater convergence in the Atlantic basin and making the AMOC reside in a stable collapsed state, i.e., the AMOC exhibits characteristics of multiple equilibria. Further analysis shows that the BS effect is much reduced under the LGM climate. This generalized indicator L has great implications for paleoclimate studies in understanding the abrupt climate change due to the instability of the AMOC.
Heteroatom Effects on Electronic Excited State Hydrogen Bonding of Fluorenone‐Based Molecular Materials
Authors: Cheng Yufei , Zhang Xiaoyu , Zhang Weiping
Published: March 2013

In this work, the geometry optimizations in the ground state and electronic excitation energies and corresponding oscillation strengths of the low‐lying electronically excited states for the isolated fluorenone (FN) and FN‐based molecular monomers, the relatively hydrogen‐bonded dimers, and doubly hydrogen‐bonded trimers, are calculated by the density functional theory and time‐dependent density functional theory methods, respectively. We find the intermolecular hydrogen bond CO···HO is strengthened in some of the electronically excited states of the hydrogen‐bonded dimers and doubly hydrogen‐bonded trimers, because the excitation energy in a related excited state decrease and electronic spectral redshift are induced. Similarly, the hydrogen bond CO···HO is weakened in other excited states. On this basis, owing to the important difference of electronegativity, heteroatoms S, Se, and Te that substitute for the O atom in the carbonyl group of the FN molecule have a significant effect on the strength of the hydrogen bond and the spectral shift. It is observed that the hydrogen bond CTe···HO is too weak to be formed. When the CS and CSe substitute for CO, the strength of the hydrogen bonds and electronic spectra frequency shift are significantly changed in the electronic excited state due to the electron transition type transformation from the ππ* feature to σπ* feature. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:153–162, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21075
Green Chemistry. Reaction of Elemental Phosphorus (P4) and Elemental Sulfur with Protonodonor Reagents: New Methods for the Synthesis of Ammonium Salts of S,S′‐Dialkyltetrathiophosphoric Acids and Octathiotetraphosphetane
Authors: Batyeva Elvira S. , Badeeva Elena K. , Platova Elena V. , Gubaidullin Aidar T. , Porch Nikki , Edwards Leslie , Malik Indranil , Frolova Liliya V. , Magedov Igor V. , Rogelj Snezna , Sinyashin Oleg G.
Published: March 2013

A new reaction of white phosphorus (P4) with elemental sulfur and thiols in the presence of different amines has been investigated. Ammonium salts of S,S′‐dialkyltetrathiophosphoric acids have been observed as main products of the reaction. Octathiotetraphosphetane ammonium salts were formed as side products. The reaction is characterized by a complete conversion of the white phosphorus and is not accompanied by the release of hydrogen sulfide. The crystal structures of both products were determined by the single crystal X‐ray diffraction. Biological activity of obtained compounds was investigated, and some promising compounds with antifungal activity identified. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:163–167, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21077
An Exploration of Parenting Behaviours and Attitudes During Early Infancy: Association with Maternal and Infant Characteristics
Authors: Arnott B. , Brown A.
Published: March 2013

The importance of warm and democratic parenting styles for optimal social, emotional and cognitive outcomes in children over the age of five is well established. However, there is a dearth of literature exploring variations in parenting styles during infancy, despite many popular parenting books aimed at this period. The primary aim of this study was to explore parenting styles in infancy and their association with infant and maternal characteristics. Five hundred and eight mothers of infants under 12 months of age completed a 36‐item questionnaire examining cognitive and behavioural aspects of early parenting (Infancy Parenting Styles Questionnaire). Items for the questionnaire were generated from popular culture early parenting books, and those raised in discussion with mothers. The underlying factor structure of the Infancy Parenting Styles Questionnaire revealed five independent factors: discipline, routine, anxiety, nurturance and involvement, which mapped onto existing concepts of warmth/nurturance and control for parenting older children, with additional constructs pertaining to the challenge of caring for young infants. Early parenting style was associated with maternal age and education, and infant birth weight, gender and age. The findings are discussed in relation to the parenting styles literature for older children and the attachment literature. Copyright © 2013 John Wiley & Sons, Ltd.
Pre‐medication with sublingual fentanyl did not relieve pain associated with bone marrow aspiration and biopsy: A randomized feasibility trial
Authors: Kuivalainen A.‐M. , Ebeling F. , Rosenberg P.H.
Published: March 2013

Background

Bone marrow aspiration and/or biopsy (BMAB) is often an unpleasant and painful procedure in spite of local anaesthetic infiltration. This randomized placebo‐controlled trial compared the pain relieving effect of sublingual fentanyl and placebo during BMAB.

Methods

One hundred sixty patients were randomized to receive either sublingual fentanyl 200 μg, 100 μg (patients ≥ 70 years old, weight ≤ 50 kg or in poor health) or placebo before BMAB. The grade of anxiety before the procedure and the grade of pain during local anaesthetic infiltration, aspiration, biopsy and immediately after the BMAB were assessed using the Numeral Rating Scale (0–10). Possible side effects of the study drugs were recorded.

Results

Sublingual fentanyl proved inadequate in relieving pain during BMAB as no significant differences in the pain scores of the fentanyl and placebo patients were observed. However, fentanyl caused significantly more dizziness than placebo.

Conclusions

The results suggest that sublingual fentanyl in a dose of 200 μg (100 μg in infirm patients) is not a feasible preventive analgesic during BMAB. Pain scores were similar and side effects more frequent in the fentanyl group than in the placebo group.
Comparative Bioavailability of Propranolol: Twice‐Daily Versus Four Times‐Daily Administration
Authors: DVORNIK D. , KRAML M. , DUBUC J. , PATTERSON‐KREUSCHER S. , MILOSOVICH G. , MULLANE J.F.
Published: March 2013

Abstract: Nineteen healthy male volunteers were given daily 160 mg propranolol hydrochloride in divided doses, either four 40‐mg tablets or two 80‐mg tablets, and the plasma propranolol concentration profiles were compared after one and seven consecutive days of drug administration. The results indicate that the relative rate and extent of propranolol absorption were greater after 80 mg given twice daily than after 40 mg given four times per day. Both differences were statistically significant at steady state attained with the seven‐day treatment. The variability in the areas under the concentration‐time curves of propranolol appeared to be smaller after the 80‐mg twice‐a‐day dosing schedule. The results are in accordance with the observed therapeutic equivalence of the two dosing regimens.
Analgesic Efficacy of Zomepirac Sodium in Patients with Pain Due to Cancer
Authors: STAMBAUGH JOHN E. , SARAJIAN CELIA
Published: March 2013

Abstract: In a single‐dose, double‐blind crossover study in 40 patients with chronic pain due to advanced cancer, zomepirac sodium (Zomax), a new, single‐entity, nonnarcotic analgesic, was compared to oxycodone with APC (Percodan) and placebo. Both a verbal and a curvilinear visual analog scale were used in the study, and the results obtained were comparable. Zomepirac sodium, 100 mg, provided analgesia equal to oxycodone with APC in all assessments of pain intensity and pain relief. The analgesic activity of zomepirac sodium was apparent by 1 hour, reached a peak between 3 and 4 hours after administration, and lasted at least 6 hours. Zomepirac sodium, 100 mg, appears to be an acceptable alternative to narcotic combinations such as oxycodone with APC in the management of moderate to severe cancer pain. The visual analog scale presented appears to be useful in the evaluation of analgesic efficacy and appears to be acceptable as an alternative to the more conventional verbal scale.
Pharmacology of Bumetanide
Authors: COHEN MICHAEL
Published: March 2013

Abstract: The diuretic action of bumetanide was compared with that of furosemide following oral and intravenous administration of equipotent doses in the rat, mouse, cat, rabbit, and dog. The onset of the bumetanide‐induced diuresis was rapid and lasted 4 to 6 hours. In studies of selective renal uptake, the ratio of tissue concentration to plasma concentration of bumetanide was three times greater than that of furosemide. Protein binding and metabolism studies did not reveal significant differences between the two diuretics. Bumetanide and furosemide were excreted in dog urine as unchanged drug. Data obtained by various procedures to determine renal sites of action indicate a direct action of bumetanide at the ascending limb of Henle's loop and the proximal convoluted tubule. The altered blood flow induced by bumetanide does not per se account for the natriuretic response, but the increase in renal electrolyte excretion is thought to be linked to a prostaglandin—reninbradykinin system.
Long‐Term Bumetanide Treatment of Patients with Edema Due to Renal Disease. Cooperative Studies
Authors: STONE WILLIAM J. , BENNETT WILLIAM M. , CUTLER RALPH E.
Published: March 2013

Abstract: Bumetanide was compared with furosemide in a total of 43 outpatients with edema due to renal disease, selected from three clinics following a uniform protocol. By random selection, 31 patients received 1 to 10 mg/day bumetanide, and 12 received 40 to 400 mg/day furosemide for at least six months. The patients were evaluated clinically, by standard laboratory tests, as well as by ECG, audiometry, eye examination, and mammary examination. Pooled statistical analysis of the results was done. Edema, body weight, and abdominal girth were reduced during both treatments. There was no significant difference in the mean response to the two diuretic agents by the two‐sided probability test in the other parameters studied, e.g., supine and standing blood pressure and pulse, serum electrolytes (sodium, potassium, chloride), and uric acid. There were no differences in liver function tests, hematology, or chest x‐ray, and no remarkable effects on hearing. Gynecomastia improved in some patients while being treated with bumetanide after spironolactone was discontinued. Adverse reactions in patients on bumetanide which were considered possibly or probably related to the drug were muscle cramps (two patients); and vertigo, headache, muscle pain, urticaria, chest pain, arthritis, dehydration, postural hypotension, and leg cramps (one each). Laboratory abnormalities in both groups were generally those that could be attributed to the pharmacologic action of the diuretics or due to the patients' underlying disease states. No drug‐related adverse effects were noted in ECG, ophthalmologic examinations, or chest x‐rays. Two patients in the furosemide group had a probably or possibly drug‐related loss of hearing sensitivity. In summary, bumetanide appeared to be as safe and as efficacious as furosemide in controlling edema and hypertension in patients with renal disease.
Intramuscular Bumetanide and Furosemide in Congestive Heart Failure
Authors: ABRAMS JONATHAN
Published: March 2013

Abstract:Bumetanide is a potent loop diuretic that acts at the ascending loop of Henle and proximal renal tubule blocking sodium reabsorption. In a study of 20 patients with congestive heart failure, using the intramuscular route, 40 mg furosemide was compared with 1 mg bumetanide. Both diuretics induced prompt diuresis and solute loss of sodium, potassium, calcium, magnesium, and chloride. In the dosages used in this protocol, furosemide was somewhat more effective than bumetanide with respect to total urine volume and the amounts of solutes excreted into the urine, and acted more rapidly. No serious side effects were observed in either group.
A Preliminary Report on the Pharmacokinetics of Saccharin in Man: Single Oral Dose Administration
Authors: COLBURN W. A. , BEKERSKY I. , BLUMENTHAL H. P.
Published: March 2013

Abstract: The pharmacokinetics of saccharin were studied in two human subjects. One male and one female subject ingested a single 100 mg oral dose of saccharin. Absorption was fast and the elimination half‐lives were 1.2 and 6.6 hours for the male and female subject, respectively. Approximately 85% of the oral dose was recovered in the urine as intact saccharin and renal clearance approximated renal plasma flow when corrected for the unbound fraction of saccharin in plasma. Saccharin elimination appears to be related to previous saccharin ingestion, suggesting a high‐retention compartment.
Merits of Adding a Beta Blocker (Acebutolol) to a Diuretic (Hydrochlorothiazide) in the Treatment of Hypertension
Authors: BELLEAU L. J. , LEBEL M. , BROSSARD J.‐J.
Published: March 2013

Abstract:In a double‐blind crossover study, the antihypertensive effect of hydrochlorothiazide alone and in combination with the beta blocker acebutolol was assessed in 18 patients suffering from mild to moderate hypertension. After a placebo period, the patients were placed on hydrochlorothiazide alone for four weeks at a dose of 50 mg daily. Acebutolol was then gradually titrated into the regimen until the optimum dose was established. The average dose was 555 mg per day, with the usual optimum dose 200 mg b.i.d. The patients then entered the crossover portion of the trial during which patients received either hydrocholorothiazide with acebutolol or hydrochlorothiazide with placebo. Each treatment period lasted six weeks. Blood pressure and heart rate were significantly lower with the combination treatment than with hydrochlorothiazide alone. At the end of each treatment period, the mean diastolic blood pressure (erect) was 90.5 mm Hg with hydrochlorothiazide—acebutolol but remained above 100 mm Hg with the diuretic alone. Neither hydrochlorothiazide nor acebutolol produced any significant changes in plasma renin activity or plasma aldosterone. There were very few side effects and no reports of bradycardia.
The Treatment of Severe Raynaud's Phenomenon with Verapamil
Authors: KINNEY EVLIN L. , NICHOLAS GARY G. , GALLO JOSEPH , PONTORIERO CHARLENE , ZELIS ROBERT
Published: March 2013

Abstract: Verapamil was evaluated in 16 patients with severe Raynaud's phenomenon. Fifty per cent of patients experienced subjective improvement by history, but only one patient had a substantial reduction in the frequency of Raynaud's phenomenon as assessed by diary analysis. We conclude that verapamil is not effective in most patients with severe Raynaud's phenomenon.
Interaction of Alcohol and Transdermally Administered Scopolamine
Authors: Gleiter Christoph H. , Antonin Karl‐Heinz , Schoenleber Wolf , Bieck Peter R.
Published: March 2013

In a placebo‐controlled, randomized, double‐blind cross‐over study in 12 healthy volunteers the effect of acute alcohol intake during treatment with transdermally administered scopolamine (TTS‐scopolamine) was investigated. One group of six subjects reached maximal blood alcohol concentrations (BAC) of 80 mg/dL and another group of six subjects a BAC of 130 mg/dL. There was no significant potentiation of alcohol effects on critical flicker fusion frequency by TTS‐scopolamine. Sensorimotor function (choice reaction task) was also not significantly more influenced by the combination. There was no effect of scopolamine on the elimination of alcohol. The urinary excretion of scopolamine was not influenced by oral intake of alcohol. TTS‐scopolamine caused only minor side effects in a few volunteers, such as dry mouth (2 of 12) and blurred vision (1 of 12).
Drug Evaluation and Registration in Hungary
Authors: Paál Tamás L. , Káldor Antal , Fäller Károly
Published: March 2013

In Hungary, the actual drug evaluation and registration system reflects international standards and national traditions. The compulsory drug registration system that was established in 1933 was among the first in Europe. Laboratory control (since 1927), clinical trials (since 1951) and human clinical pharmaceutical experiments (since 1967) are prerequisites for new‐drug approval. Applications should be sent to the National Institute of Pharmacy, which has the overall responsibility for the registration of pharmaceutical products. Applications are assessed on the basis of the drug's quality, safety, and efficacy. The procedure follows several steps: evaluation of chemical and pharmaceutical data by the staff of the National Institute of Pharmacy; evaluation of toxicologic and pharmacologic documentation with the help of the Committee on Drug Administration; after consultation with the Committee on Medical Research Ethics (mandatory in cases of original new drugs), authorized clinical pharmacologic investigations are conducted in the units of the Clinical Pharmacological Network, which are supervised by the National Center for Clinical Pharmacology; clinical trials; application for registration (scientific evaluation); and finally, application to the Ministry of Health for a marketing authorization. The process may be facilitated appreciably for preparations already registered in another country. Moreover, Hungary is an active member in the World Health Organization (WHO), Pharmaceutical Inspection Convention of the European Free Trade Association (EFTA PIC), the Council of Mutual Economic Assistance (COMECON), and other international pharmaceutical and clinical pharmaceutical collaborations.
The New Monobactams: Chemistry and Biology
Authors: Sykes Richard B. , Koster William H. , Bonner Daniel P.
Published: March 2013

The discovery of the monobactams led to the successful development of aztreonam as the first of this novel class of beta‐lactam antibiotics to enter the clinical field. Continued structural modification on the monobactam nucleus has resulted in two additional compounds from this class that show interesting biologic properties. The first, SQ 83,360, is like aztreonam in exhibiting high activity against members of the Enterobacteriaceae but has the added characteristic of being exceptionally active against strains of Pseudomonas aeruginosa. Also, significant gains are made with SQ 83,360 in activity against Pseudomonas spp. and Acinetobacter. The second compound, tigemonam, is also like aztreonam, having good activity against Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae and showing good beta‐lactam stability. Tigemonam differs from aztreonam in being well absorbed orally by experimental laboratory animals.
BOOK REVIEWS
Authors: Cavaliere M. Beth
Published: March 2013

Book reviewed in this article:

Drug Resistance in Viruses, Other Microbes and Eukaryotes Edited by J. S. Oxford et al

Pharmacology in Medicine: Principles and Practice Edited by Sachin N. Pradhan, et al.

Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring Edited by W. E. Evans, et al.

Opioid Analgesics Chemistry and Receptors By A. F. Casy and R. T. Parfitt

Myocardial and Skeletal Muscle Bioenergetics Edited by Nachman Brantbar

Geriatric Clinical Pharmacology Edited by W. G. Wood and R. Strong

Handbook of Behavioral Teratology Edited by E. P. Riley and C. V. Vorhees

Anti‐inflammatory Compounds Edited by W. R. Nigel Williamson

Molecular and Cellular Mechanisms of Anesthetics Edited by S. H. Roth and K. W. Miller
Anorectic Drugs: Drug Policy Making at the State Level
Authors: Richard Barbara W. , Lasagna Louis
Published: March 2013

This study outlines the attempts of four states (Louisiana, Kansas, Wisconsin, and Michigan) to restrict anorectic prescriptions. The actions in these four states exemplify the various mechanisms used in regulating anorectics, ranging from educational efforts to legislative enactments. We examine the evidence used in promulgating these policies and review some of the current literature on the safety and efficacy of anorectics. Despite the existence of evidence demonstrating the safety and efficacy of anorectics, the states seem to be moving toward more severe restrictions, in contrast to the federal regulatory agencies.
Superactivated Charcoal Versus Cholestyramine for Cholesterol Lowering: A Randomized Cross‐Over Trial
Authors: Park Glen D. , Spector Reynold , Kitt Therese M.
Published: March 2013

To evaluate the relative abilities of superactivated charcoal (20 g twice daily) and cholestyramine (8 g twice daily) to lower plasma cholesterol concentrations acutely, six hyper‐cholesterolemic patients were studied using a randomized cross‐over design. After a 1‐week dietary control period, each subject received 3 weeks of each treatment regimen on separate occasions. Superactivated charcoal and cholestyramine reduced total plasma cholesterol by 21.8 ± 3.8% and 16.2 ± 2.4%, respectively. Side effects were mild and similar for both treatments. At the dosage regimens studied, superactivated charcoal and cholestyramine have comparable ability to lower plasma cholesterol concentrations.
Pharmacokinetics and Pharmacodynamics of Urapidil in Severe Hypertension
Authors: Bottorff Michael B. , Hoon Timothy J. , Rodman John H. , Gerlach Paul A. , Ramanathan K. B.
Published: March 2013

The clinical response and pharmacokinetics of intravenous urapidil were studied in patients with uncontrolled severe hypertension. Six of nine patients achieved a diastolic blood pressure (DBP) of 100 mm Hg after initial administration of serial bolus doses and were then placed on maintenance infusions. Three of these six patients maintained a DBP 100 mm Hg or lower at infusion rates of 10 to 20 mg/hr, whereas the remaining three patients experienced a loss of DBP control despite rates of 40 mg/hr. Mean DBP was significantly reduced from 126 ± 6 mm Hg (N = 9) to 105 ± 15 mm Hg after the bolus phase (N = 9, P < .05) and 99 ± 18 mm Hg after the infusion phase (N = 6, P < .05). Significant reductions in systolic blood pressure were also achieved after bolus and infusion phases. Adverse reactions included drowsiness, tachycardia, nausea and vomiting but were considered mild. Estimated pharmacokinetic parameters included Vz (0.80 ± 0.20 L/kg), CL (2.53 ± 0.99 mL/min/kg) and t1/2 (4.0 ± 1.5 hr). Urapidil safely reduces blood pressure in patients with severe hypertension. An alternative dosing regimen is suggested.
The Influence of Hydrochlorothiazide and Tripamide on Serum and Urinary Amylase
Authors: Conrad Kenneth A. , Fagan Timothy C. , Simons Jarid A.
Published: March 2013

Pancreatitis and asymptomatic elevations of serum amylase have been reported after therapy with thiazide diuretics. In the current study, the effects of hydrochlorothiazide and tripamide treatment on serum and urinary amylase excretion were investigated in 12 hypertensive volunteers. Two patients developed modest elevations of the serum amylase above the normal range after 12 weeks of treatment with hydrochlorothiazide 50 mg daily, but the mean serum amylase did not change. Hydrochlorothiazide did not produce a statistically significant increase in urinary amylase excretion but did reduce the ratio of salivary amylase/creatinine clearance in a two‐hour urine collection. Tripamide 10 mg daily had no effect on serum or urinary amylase.
Secretion of Dilevalol in Breast Milk
Authors: Radwanski Elaine , Nagabhushan Nagamani , Affrime Melton B. , Perentesis George , Symchowicz Samson , Patrick James E.
Published: March 2013

The pharmacokinetics of unchanged and total (unchanged plus Glusulase [Biotechnology Systems, Boston, MA]) released dilevalol and secretion into human breast milk was studied in six healthy breast‐feeding female volunteers administered a single 400‐mg dilevalol hydrochloride capsule. In plasma, the mean Cmax for unchanged dilevalol, 485 ng/mL was reached at 0.8 hour (tmax) and the AUC(48 hours) was 1435 hr × ng/mL. Pharmacokinetic analysis of unchanged dilevalol in plasma showed that dilevalol was distributed and eliminated with half‐lives of 0.9 and 8.2 hours, respectively. Breast milk concentrations of unchanged dilevalol as a function of time, paralleled those of plasma but were consistently lower. The milk Cmax, 149 ng/mL, occurred during the 0 to 2 hour collection interval; the AUC(42 hours) for unchanged dilevalol in milk was 663 hr × ng/mL. The mean milk to plasma concentration ratio was 0.46. The unchanged dilevalol plasma concentrations were 12 to 18% those of total drug suggesting that the drug is extensively conjugated. By contrast, the concentrations of unchanged dilevalol in breast milk, based on Cmax and AUC data were 63 to 94% those of total drug, indicating that very little conjugated drug is secreted into breast milk. Through 48 hours, a mean of only 27 μg dilevalol or 0.007% of the administered dose was secreted into breast milk, which is much less than that reported for other beta blockers.
Antipyrine Pharmacokinetics in Women Receiving Conjugated Estrogens
Authors: Scavone Joseph M. , Greenblatt David J. , Blyden Gershwin T.
Published: March 2013

The pharmacokinetics of a single 1.0 to 1.2‐g intravenous dose of antipyrine was studied in 22 healthy female volunteers aged 28 to 70 years (mean, 45 years). Eleven subjects had been taking a conjugated estrogen preparation for at least 3 months; the other 11 subjects who were not taking conjugated estrogens and who were matched for age, weight, and smoking patterns, served as a control group. Plasma antipyrine concentrations were determined by high‐pressure liquid chromatography (HPLC) in multiple plasma samples drawn 24 to 48 hours after dosage. Mean ± SE pharmacokinetic variables in control and conjugated‐estrogen groups were volume of distribution, 0.57 ± 0.02 versus 0.56 ± 0.02 L/kg; elimination half‐life, 11.0 ± 0.82 versus 12.6 ± 0.89 hours; and clearance, 0.63 ± 0.06 versus 0.54 ± 0.03 mL/min/kg. None of the differences was significant. Although antipyrine clearance is significantly impaired by oral contraceptives, there is no evidence of altered antipyrine pharmacokinetics from treatment with conjugated estrogens.
Ambulatory Blood Pressure Monitoring for Evaluation and Management of Hypertensives: Effect on Outcome and Cost Effectiveness
Authors: Carr Albert A. , Bottini P. Bruce , Prisant L. Michael
Published: March 2013

Blood pressure monitoring of hypertensives in the ambulatory state by automated portable devices (ABPM) as compared with casual office readings (COBPM) may predict outcome with greater precision and at an overall lower cost. Prospective trials that in random fashion require evaluation and management decisions on the basis of ABPM compared with COBPM are required to determine whether the above is true. End points such as death, stroke, or myocardial infarction occur at a low frequency rate. This would require thousands of patients to be followed 5 or more years to determine if evaluation and management by ABPM compared with COBPM results in a different outcome. A much smaller population can be used if end points are changes in left ventricular mass and left ventricular ischemia, arterial wall stiffness and thickness, endogenous creatinine clearance, renal albumin excretion, antihypertensive drug requirements, and adverse reactions. Until results from such a prospective trial are available, COBPM is the method of choice for evaluation and management of hypertensives. Automated blood pressure measurement can provide useful information in special circumstances and is of value for research purposes.
Hair Analysis of Cocaine: Differentiation Between Systemic Exposure and External Contamination
Authors: Koren Gideon , Klein Julia , Forman Rachel , Graham Karen
Published: March 2013

Cocaine has been shown to accumulate in hair of admitted users. Before using this test to verify cocaine use, however, it is crucial to differentiate between systemic exposure and external contamination from being in contact with crack smoke. In the present studies, the authors document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair. External contamination with crack smoke is washable, whereas systemic exposure is not. The authors suggest these two criteria to distinguish systemic exposure from external contamination.
Pharmacokinetics of Acetazolamide in Healthy Volunteers after Short‐ and Long‐Term Exposure to High Altitude
Authors: Ritschel Wolfgang A. , Paulos Claudio , Arancibia Aquiles , Agrawal Mukul A. , Wetzelsberger Klaus M. , Lücker Peter W.
Published: March 2013

Exposure to high altitude results in significant physiologic changes and may precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of meperidine were observed after exposure to high altitude. This study was conducted to investigate whether similar changes occur for acetazolamide, which is prescribed for prophylaxis of acute mountain sickness. Acetazolamide 250 mg was administered orally to young, healthy male volunteers in groups of 12 each: those residing at sea level (group L), these same volunteers on the day after arrival at high altitude (4,360 m, group HA), and volunteers living at high altitude for 10 months or longer (group HC). Serial blood samples were collected for 24 hours and acetazolamide concentrations were measured in whole blood, plasma, and plasma water. The elimination rate constant (λZ) was significantly increased in group HA compared with group L. Clearance uncorrected for bioavailability (Cl/F) increased significantly in group HA compared with group L, and further increased in group HC. Apparent volume of distribution (VZ/F) was decreased by 17% in group HA compared with group L, and increased by 37% in group HC compared with group HA. Mean residence time (MRT) was significantly decreased in group HA compared with groups L and HC. Erythrocyte (RBC) uptake increased significantly after a significant increase in RBC count in group HC compared with group L. The extent of protein binding (EPB), however, was significantly decreased in group HA compared with groups L and HC. Free acetazolamide concentrations were significantly lower in group HC than in group L 12 hours after administration. Based on these observations, it is suggested that patients travelling to high altitude, especially altitudes above 4,000 m, should be closely monitored and acetazolamide dosage adjusted as necessary.
Imaging directed photothermolysis through two‐photon absorption demonstrated on mouse skin – a potential novel tool for highly targeted skin treatment
Authors: Wang Hequn , Zandi Soodabeh , Lee Anthony M.D. , Zhao Jianhua , Lui Harvey , McLean David I. , Zeng Haishan
Published: March 2013

One‐photon absorption based traditional laser treatment may not necessarily be selective at the microscopic level, thus could result in un‐intended tissue damage. Our objective is to test whether two‐photon absorption (TPA) could provide highly targeted tissue alteration of specific region of interest without damaging surrounding tissues. TPA based laser treatments (785 nm, 140 fs pulse width, 90 MHz) were performed on ex vivo mouse skin using different average power levels and irradiation times. Reflectance confocal microscopy (RCM) and combined second‐harmonic‐generation (SHG) and two‐photon fluorescence (TPF) imaging channels were used to image before, during, and after each laser treatment. The skin was fixed, sectioned and H & E stained after each experiment for histological assessment of tissue alterations and for comparison with the non‐invasive imaging assessments. Localized destruction of dermal fibers was observed without discernible epidermal damage on both RCM and SHG + TPF images for all the experiments. RCM and SHG + TPF images correlated well with conventional histological examination. This work demonstrated that TPA‐based light treatment provides highly localized intradermal tissue alteration. With further studies on optimizing laser treatment parameters, this two‐photon absorption photothermolysis method could potentially be applied in clinical dermatology. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Similarities and Differences of Systematic Consensus on Disaster Mental Health Services Between Japanese and European Experts
Authors: Fukasawa Maiko , Suzuki Yuriko , Nakajima Satomi , Narisawa Tomomi , Kim Yoshiharu
Published: March 2013

We recently developed new disaster mental health guidelines in Japan through the Delphi process, a method for building consensus among experts, using as a reference the guidelines developed by The European Network for Traumatic Stress (TENTS) in Europe. We included in our survey 30 items used in the TENTS survey, 20 of which achieved positive consensus in that survey. Here we report on the extent of agreement of 95 Japanese experts on each of these 30 items and examine the reasons for disagreements with the TENTS survey results based on the comments obtained from the participants of our survey. Of the 20 items, 12 also gained consensus in our survey and 1 additional item achieved consensus that did not achieve it in the TENTS survey. Items that did not gain consensus in our survey, but did in the TENTS survey, were recommendations for close collaboration with the media, screening volunteers for their suitability, and withholding formal screening of the affected population. The need for specialist care for specific populations was endorsed in our survey, but not in the TENTS survey. Overall, the opinion of Japanese experts was congruent with that of Western experts, but some guideline amendments would be beneficial.
Cross‐linked hydrogel and polyester resorbable ventilation tubes in a chinchilla model
Authors: Park Albert H. , Hoyt David , Britt David , Chase Shane , Tansavatdi Kristina , Hunter Lisa , McGill Lawrence , Sheng Xiaoming , Skardal Aleksander , Prestwich Glenn D.
Published: March 2013

Objectives/Hypothesis:

To determine the resorption rate and biocompatibility characteristics of novel cross‐linked hydrogel ventilation tubes and varied formulations of polyester ventilation tubes in a Chinchilla model.

Study Design:

Animal Study.

Methods:

Three cross‐linked glycosaminoglycan hydrogel ventilation tubes fabricated by cross‐linking thiol‐modified chondroitin sulfate or thiol‐modified carboxymethylated hyaluronic acid, four different polyester ventilation tubes (poly L‐lactide [PLA], 50/50 poly D,L‐lactide‐co‐glycolide [PLGA], and silver‐impregnated versions of PLA and PLGA tubes) were placed into the tympanic membranes of chinchillas. Commercially available fluoroplastic ventilation tubes were placed in the contralateral ear of each animal to serve as a control. Integrity of the tubes was assessed by weekly otoscopy. Biocompatibility was assessed by auditory brainstem response, by otoscopic and histologic examination of the tympanic membrane at the tube site.

Results:

The hydrogel tubes had very short resorption times that expanded and enlarged the myringotomy site. PLGA and silver‐coated PLGA tubes maintained their integrity in the tympanic membrane for similar durations of 18.9 ± 6.4 days and 21.0 ± 6.0 days, respectively. The silver‐coated PLGA tubes had lower neutrophil and fibrosis scores than PLGA tubes. PLA tubes demonstrated equivalent findings to commercially available nonresorbable tubes with respect to otoscopic findings, auditory brainstem response thresholds, and histologic inflammatory scores.

Conclusions:

Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable tubes. Silver modification may confer some stability to PLGA tubes. Hydrogel tubes have very short resorption times, tend to enlarge the myringotomy site, and show greater inflammatory changes.
Fluorescent Polymeric Micelles with Aggregation‐Induced Emission Properties for Monitoring the Encapsulation of Doxorubicin
Authors: Chen Jen‐Ing , Wu Wen‐Chung
Published: March 2013

A new type of fluorescent polymeric micelles is developed by self‐assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)‐b‐poly[styrene‐co‐(2‐(1,2,3,4,5‐pentaphenyl‐1H‐silol‐1‐yloxy)ethyl methacrylate)] [PEG‐b‐P(S‐co‐PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX‐loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX‐loaded micelles.

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Polysaccharides and Their Derivatives for Versatile Tissue Engineering Application
Authors: Khan Ferdous , Ahmad Sheikh Rafi
Published: March 2013

Research and development in the design, synthesis, modification, evaluation, and characterization of polysaccharide‐based bioactive polymeric materials for guiding and promoting new tissue in‐growth is reviewed. Emphasis is given in this interdisciplinary field of tissue engineering (TE) with particular reference to bone, cartilage, and skin TE. Current strategies in scaffold‐guided TE approaches using polymers of natural origin and their composites are elaborated. Innovative modification techniques in creating functional materials for advanced TE applications are presented. Challenges and possible solutions in the technological innovation in factor molecules incorporation and surface functionalization for improving the fabrication of biomaterials scaffolds for cost‐effective TE are also presented.

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