bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acetaminophen/paracetamol: A history of errors, failures and false decisions
Authors: Brune K. , Renner B. , Tiegs G. 
Published: December 2014

AbstractAcetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existed to renowned researchers having contributed to the medical use of paracetamol and its precursors as H.U. Zollinger, S. Moeschlin, U. Dubach, J. Axelrod and others. Further information is found in earlier reviews by Eichengrün, Rodnan and Benedek, Sneader, Brune; comp. references. The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side‐effect ‘epidemy’ (phenacetin nephropathy, drug‐induced interstitial nephritis) and ends with the discovery of second‐generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N‐acetyl‐p‐benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound.
New results on the sum of Gamma random variates with application to the performance of wireless communication systems over Nakagami‐m fading channels
Authors: Ansari Imran Shafique , Yilmaz Ferkan , Alouini Mohamed‐Slim , Kucur Oğuz 
Published: December 2014

AbstractThe probability density function (PDF) and cumulative distribution function of the sum of L‐independent but not necessarily identically distributed Gamma variates, applicable to the output statistics of maximal ratio combining receiver operating over Nakagami‐m fading channels or in other words to the statistical analysis of the scenario where the sum of squared Nakagami‐m distributions is user‐of‐interest, are presented in closed form in terms of well‐known Meijer's G function and easily computable Fox's H̄ function for integer‐valued and non‐integer‐valued m fading parameters. Further analysis, particularly on bit error rate via a PDF‐based approach, is also offered in closed form in terms of Meijer's G function and Fox's H̄ function for integer‐valued fading parameters and extended Fox's H̄ function (
) for non‐integer‐valued fading parameters. Our proposed results complement previous known results that are either expressed in terms of infinite sums, nested sums or higher‐order derivatives of the fading parameter m. Copyright © 2014 John Wiley & Sons, Ltd.
Essential oil chemotypification and secretory structures of the neglected vegetable Smyrnium olusatrum L. (Apiaceae) growing in central Italy
Authors: Maggi Filippo , Papa Fabrizio , Giuliani Claudia , Maleci Bini Laura , Venditti Alessandro , Bianco Armandodoriano , Nicoletti Marcello , Iannarelli Romilde , Caprioli Giovanni , Sagratini Gianni , Cortese Manuela , Ricciutelli Massimo , Vittori Sauro 
Published: December 2014

AbstractAs part of our research on local plants, including neglected horticultural crops to be rediscovered as culinary vegetables, we focused on Smyrnium olusatrum, a biennal herb used in cuisine for many centuries by Romans that has now been replaced by celery. We investigated the essential oil compositions of different plant organs collected in 18 populations of central Italy (Marche, Umbria, Abruzzo, Tuscany and Latium) by gas chromatography (GC) with a flame ionization detector and GC with mass spectrometry (MS) to identify the main chemotypes that occur. Owing to the presence of thermosensitive molecules such as isofuranodiene, curzerene and germacrone undergoing Cope‐rearrangement during the GC run, a truthful quantitative determination of these constituents was accomplished by high‐performance liquid chromatography with a diode‐array detector (HPLC‐DAD). Chemical data were supported by a chemometric technique in the form of principal component analysis, which allowed identification of chemical differences among organs. Furanosesquiterpenoids were the main fraction of the oils, with isofuranodiene as the most abundant in flowers and roots, furanoeremophil‐1‐one in leaves and roots and 1‐β‐acetoxyfuranoeudesm‐4(15)‐ene in fruits. To complete the phytochemical analysis, polar compounds such as chlorogenic acid, isoquercitin, 3‐indoleacetic acid and saccharose were isolated from the ethanolic extracts of the plant by column chromatography and structurally elucidated by nuclear magnetic resonance. Moreover, a morphological and histochemical survey on the secretory structures was performed, with the special aim to localize the sites of terpenes biosynthesis in both above‐ and belowground organs. Overall, the results can be considered important in the light of the recent interest in neglected edible plants for botanical food supplements and functional foods market. Copyright © 2014 John Wiley & Sons, Ltd.
Novel CLC3 transcript variants in blood eosinophils and increased CLC3 expression in nasal lavage and blood eosinophils of asthmatics
Authors: Gaurav Rohit , Bewtra Againdra K. , Agrawal Devendra K. 
Published: December 2014

AbstractEosinophilia is a characteristic feature of allergic airway inflammation and remodeling. Chloride channel‐3 (CLC3) in eosinophils has been associated with superoxide generation and respiratory burst. The CLC3 gene may produce multiple transcript variants through alternative splicing. However, the presence of CLC3 variants in human eosinophils is unknown. We examined the expression of CLC3 transcript variants in peripheral blood eosinophils of allergic asthmatics and healthy individuals. Potential of these obligatory dimers to form homo‐ or hetero‐dimers was examined in HEK293 cells co‐transfected with CLC3b‐GFP and CLC3e‐RFP. Eosinophils were isolated from peripheral blood by negative selection. Expression of CLC3 and CLC3 transcript variants was examined by qPCR, Western blot, and immunofluorescence. Confocal micrographs were analyzed with Image J software. Higher levels of novel transcript variants of CLC3 (CLC3b and CLC3e) were found in peripheral blood eosinophils of asthmatics compared to healthy non‐atopic subjects. We also found higher CLC3 protein expression in the blood and nasal lavage eosinophils of asthmatics than healthy subjects. Both membranous and intracellular CLC3 expression were observed. Also, we found the presence of both homodimers and heterodimers of CLC3b‐GFP and CLC3e‐RFP in HEK293 cells. Higher and differential expression of novel CLC3 transcript variants in mild‐to‐moderate and moderate‐to‐severe asthmatic eosinophils suggest their critical role in allergic asthma. Membranous and intracellular (granular) expression of CLC3 in nasal lavage and peripheral blood eosinophils suggest their involvement in the activation and migration of eosinophils in allergic asthma. Moreover, homo‐ and hetero‐dimerization of these transcript variants may change the channel properties to exhibit these states. Presence of CLC3 variants may serve as a biomarker in allergic asthma and additional knowledge of interaction between CLC3 transcript variants and their specific role in the activation and migration of eosinophils will allow to explore novel therapeutic approach in allergic asthma.
A positive genotype–phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo‐pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene
Authors: Thiele Susanne , Werner Ralf , Grötzinger Joachim , Brix Bettina , Staedt Pia , Struve Dagmar , Reiz Benedikt , Farida Jennane , Hiort Olaf 
Published: December 2014

AbstractMaternally inherited inactivating GNAS mutations are the most common cause of parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO) leading to pseudohypoparathyroidism type Ia (PHPIa) due to Gsα deficiency. Paternally inherited inactivating mutations lead to isolated AHO signs characterizing pseudo‐pseudohypoparathyroidism (PPHP). Mutations are distributed throughout the Gsα coding exons of GNAS and there is a lack of genotype–phenotype correlation. In this study, we sequenced exon 1–13 of GNAS in a large cohort of PHPIa‐ and PPHP patients and identified 58 different mutations in 88 patients and 27 relatives. Thirty‐three mutations including 15 missense mutations were newly discovered. Furthermore, we found three hot spots: a known hotspot (p.D190MfsX14), a second at codon 166 (p.R166C), and a third at the exon 5 acceptor splice site (c.435 + 1G>A), found in 15, 5, and 4 unrelated patients, respectively. Comparing the clinical features to the molecular genetic data, a significantly higher occurrence of subcutaneous calcifications in patients harboring truncating versus missense mutations was demonstrated. Thus, in the largest cohort of PHPIa patients described to date, we extend the spectrum of known GNAS mutations and hot spots and demonstrate for the first time a correlation between the genetic defects and the expression of a clinical AHO‐feature.
Balance of Academic Responsibilities of Clinical Track Pharmacy Faculty in the United States: A Survey of Select American College of Clinical Pharmacy Practice and Research Network Members
Authors: Nutescu Edith A. , Engle Janet P. , Bathija Sacheeta , Grim Shellee A. , Chan Juliana , Mucksavage Jeffrey J. , Ohler Kirsten H. , Tesoro Eljim P. , Thielke James J. , Shapiro Nancy L. , Donnelly Andrew J. , Garofalo John , DiDomenico Robert J. 
Published: December 2014

Study ObjectivesTo characterize the balance of clinical and academic responsibilities of clinical track pharmacy faculty in the United States and evaluate organizational structures that promote satisfactory balance between these responsibilities.DesignProspective cross‐sectional survey.SettingA 22‐item online survey was developed and distributed via Qualtrics software.ParticipantsClinical faculty members of the American College of Clinical Pharmacy Adult Medicine, Ambulatory Care, Cardiology, Critical Care, Gastrointestinal/Liver/Nutrition, Immunology/Transplantation, Infectious Disease, and Pediatrics Practice and Research Networks (PRNs) were invited to participate via the PRN electronic mailing list.Measurements and Main ResultsThe survey comprised questions related to demographics, organizational structure, and balance of clinical and academic responsibilities. A total of 344 participants responded to some or all of the survey questions. The demographics were relatively equally balanced between faculty at state and private academic institutions, academic rank, and practice setting. Expected and actual effort allocations were similar for each of the clinical and academic responsibilities, with direct patient care and clinical teaching representing more than 50% effort allocation cumulatively. Clinical faculty at state institutions devoted a larger proportion of time to clinical service, whereas clinical faculty at private institutions devoted a greater proportion of time to didactic teaching. When asked about time constraints, 157 (69.8%) of the 225 survey participants responding to this question did not believe they had sufficient time to fulfill their nonclinical academic needs. Clinical faculty who were provided “protected time” away from clinical service had a significantly more favorable opinion of this question.ConclusionMost of the clinical track pharmacy faculty indicated that they have insufficient time to fulfill their nonclinical academic responsibilities. Provision of protected time may alleviate some of these time constraints.
Successful Use of Tetrabenazine in a Patient with Intractable Hiccups After Stroke
Authors: Naro Antonino , Bramanti Placido , Calabrò Rocco Salvatore 
Published: December 2014

A hiccup is a myoclonic jerk of the diaphragm, and cases of hiccups may last for more than 48 hours (persistent hiccups) or even more than 2 months (intractable hiccups). Current pharmacologic treatment of persistent or intractable hiccups mainly includes antidopaminergic drugs. We describe the case of a 60‐year‐old man with a recent diagnosis of right insular ischemic stroke who presented with frequent, intense, and disabling hiccups for more than 1 month. As diagnosis of poststroke hiccups was assumed, the patient was treated over the next 6 months with adequate doses of various antipsychotic drugs commonly used for the treatment of hiccups; however, all were discontinued because of adverse effects. Indeed, dyskinesia after chlorpromazine (up to 75 mg/day for 4 wks), as well as somnolence and dyskinesia after haloperidol (up to 6 mg/day for 6 wks), somnolence after gabapentin (up to 1800 mg/day for 8 wks), and severe somnolence and hypotension after baclofen (up to 50 mg/day for 6 wks) were reported. The patient was then prescribed tetrabenazine at a starting dose of 12.5 mg twice/day (25 mg/day), with a nearly complete remission of the hiccup symptomatology after ~6 weeks, when a daily dose of 150 mg was reached. We therefore hypothesize that a supratentorial lesion may disrupt the modulation of dopaminergic pathways involved in the regulation of medullar centers responsible for the hiccup reflex. To our knowledge, this is the first case report of poststroke hiccups responding to tetrabenazine. The dramatic response of our patient to tetrabenazine monotherapy suggests that this drug may be a valuable pharmacologic alternative for patients with hiccups after stroke who are intolerant or unresponsive to classic antipsychotic agents.
Intraluminal proteome and peptidome of human urinary extracellular vesicles
Authors: Liu Xinyu , Chinello Clizia , Musante Luca , Cazzaniga Marta , Tataruch Dorota , Calzaferri Giulio , James Smith Andrew , De Sio Gabriele , Magni Fulvio , Zou Hequn , Holthofer Harry 
Published: December 2014

PurposeUrinary extracellular vesicles (UEVs) are a novel source for disease biomarker discovery. However, Tamm–Horsfall protein (THP) is still a challenge for proteomic analysis since it can inhibit detection of low‐abundance proteins. Here, we introduce a new approach that does not involve an ultracentrifugation step to enrich vesicles and that reduces the amount of THP to manageable levels.Experimental designUEVs were dialyzed and ultrafiltered after reduction and alkylation. The retained fraction was digested with trypsin to reduce the remaining THP and incubated with deoxycholate (DOC). The internal peptidome and internal proteome were analyzed by LC‐ESI‐MS.ResultsA total of 942 different proteins and 3115 unique endogenous peptide fragments deriving from 973 different protein isoforms were identified. Around 82% of the key endosomal sorting complex required for transport components of UEVs generation could be detected from the intraluminal content.Conclusions and clinical relevanceOur UEVs preparation protocol provides a simplified way to investigate the intraluminal proteome and peptidome, in particular the subpopulation of UEVs of the trypsin‐resistant class of exosomes (positive for tumor susceptibility gene101) and eliminates the majority of interfering proteins such as THP. This method allows the possibility to study endoproteome and endopeptidome of UEVs, thus greatly facilitating biomarker discovery.
Immunological detection of glutamyl aminopeptidase in urine samples from cisplatin‐treated rats
Authors: Montoro‐Molina Sebastián , Quesada Andrés , Zafra‐Ruiz Piedad V. , O'Valle Francisco , Vargas Félix , de Gracia María del Carmen , Osuna Antonio , Wangensteen Rosemary 
Published: December 2014

PurposeThe aim of this work is to demonstrate if urinary excretion of glutamyl aminopeptidase (GluAp) can be quantified by immunological methods.Experimental designUrine samples from control and cisplatin‐treated rats (n = 10 each group) were obtained at 1, 8, and 15 days after cisplatin injection. GluAp was analyzed by kinetic fluorimetry, ELISA, and immunoblotting. Sensitivity and specificity was studied for fluorimetric activity and ELISA 24 h after cisplatin injection. We also analyzed the predictive value over renal dysfunction at the end of the experiment.ResultsGluAp was easily detected by immunoblotting and ELISA, and its urinary excretion was increased in cisplatin‐treated rats (p < 0.01). Results obtained with ELISA were strongly correlated (r = 0.8186; p < 0.0001) with fluorimetric activity. Kinetic fluorimetry was the method with the highest AUC (AUC = 1) and the highest predictive value over serum creatinine (r = 0.7630; p = 0.0001) and body weight increase (r = –0.8721; p < 0.0001).Conclusions and clinical relevanceGluAp can be detected in urine samples with immunological methods, making possible the development of an antibody‐based kit for its determination. Its excretion correlates with the extent of renal dysfunction in cisplatin‐treated rats, confirming its value as an early marker of renal damage that can be a diagnostic aid in renal diseases.
Chemistry of Sumanene
Authors: Amaya Toru , Hirao Toshikazu 
Published: December 2014

AbstractSumanene (C21H12) is a bowl‐shaped π‐conjugated molecule with C3v symmetry, consisting of alternating benzene rings and cyclopentadiene rings around the central benzene ring. The structure corresponds to the smallest C3v‐symmetric fragment for the structural motifs of fullerenes or end‐caps of carbon nanotubes. The presence of three sp3‐hybridized benzylic sites is one of the most characteristic structural features in sumanene, which allows the different chemistry from that of corannulene. Since our first synthesis in 2003, we have engaged in the study of sumanene. This article summarizes our continuous study, including the synthesis, structure, dynamics, derivatization, complexation with transition metals, charge carrier mobility, and conversion to nitrogen‐doped graphitic carbon, of sumanene.
The neurotoxicity of amphetamines during the adolescent period
Authors: Teixeira‐Gomes Armanda , Costa Vera Marisa , Feio‐Azevedo Rita , Bastos Maria de Lourdes , Carvalho Félix , Capela João Paulo 
Published: December 2014

AbstractAmphetamine‐type psychostimulants (ATS), such as amphetamine (AMPH), 3,4‐methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) are psychoactive substances widely abused, due to their powerful central nervous system (CNS) stimulation ability. Young people particularly use ATS as recreational drugs. Moreover, AMPH is used clinically, particularly for attention deficit hyperactivity disorder, and has the ability to cause structural and functional brain alterations. ATS are known to interact with monoamine transporter sites and easily diffuse across cellular membranes, attaining high levels in several tissues, particularly the brain. Strong evidence suggests that ATS induce neurotoxic effects, raising concerns about the consequences of drug abuse.Considering that many teenagers and young adults commonly use ATS, our main aim was to review the neurotoxic effects of amphetamines, namely AMPH, MDMA, and METH, in the adolescence period of experimental animals. Reports agree that adolescent animals are less susceptible than adult animals to the neurotoxic effects of amphetamines. The susceptibility to the neurotoxic effects of ATS seems roughly located in the early adolescent period of animals. Many authors report that the age of exposure to ATS is crucial for the neurotoxic outcome, showing that the stage of brain maturity has a strong importance. Moreover, recent studies have been undertaken in young adults and/or consumers during adolescence that clearly indicate brain or behavioural damage, arguing for long‐term neurotoxic effects in humans. There is an urgent need for more studies during the adolescence period, in order to unveil the mechanisms and the brain dysfunctions promoted by ATS.
Efficacy of exogenous xylanases for improvingin vitrofermentation of forages
Authors: HE Z. X. , YANG L. Y. , YANG W. Z. , BEAUCHEMIN K. A. , TANG S. X. , HUANG J. Y. , ZHOU C. S. , HAN X. F. , WANG M. , KANG J. H. , ODONGO N. E. , TAN Z. L. 
Published: December 2014

SUMMARYBatch cultures of mixed rumen micro-organisms were used to evaluate varying enzyme products with high xylanase activity (EPX), four of which were recombinant single xylanase activity developmental enzyme products (EPX1–EPX4, products of xylanase genes derived fromTrichoderma harzianum, Trichoderma reesei, OrpinomycesandAspergillus oryzae, respectively), for their potential to improvein vitroruminal fermentation of three forages [maize (Zea mays) stover (MS), rice (Oryza sativa) straw (RS) and Guimu No. 1 grass (Pennisetum americanum×Pennisetum purpureum, GM)]. The enzyme product EPX5, derived fromTrichoderma longibrachiatum, was used as a positive control that could improvein vitrofermentation of forages. Enzymes were supplied at dose rates of 0 (control), 20 (low), 50 (medium) and 80 (high) enzymic units of xylanase/g of dry matter (DM). There were no interactions between EPX and dose for the fermentation characteristics evaluated. Increasing EPX dose linearly increased gas production (GP) kinetic characters [i.e. asymptotic GP (VF), half time when GP is half of the theoretical maximum GP (t0·5), and initial fractional rate of degradation (FRD0)] and methane (CH4) production from RS and GM at 24 h, and increased degradability of DM at 24 h for MS and RS. A linear increase in degradability of neutral detergent fibre (NDF) of the three forages at 24 h was observed with increasing dose of EPX, but at 48 h only NDF degradability of RS was increased. There were differences in the effects of EPX on degradability of DM and NDF from RS at 24 h, with EPX4 having the highest and EPX1 having the lowest. In addition, increasing EPX dose linearly increased acetate proportion at 24 h and total volatile fatty acids (TVFA) at 48 h in MS. Increasing EPX dose linearly increased TVFA at 24 h, and ammonia-nitrogen (NH3-N) concentration at 48 h in RS. For GM, linear or quadratic effects of dose on acetate and butyrate concentration were observed at 24 and 48 h. The present study indicates that applying EPX to low-quality forages has the potential to improve rumen degradability and utilization. Furthermore, EPX from different sources differed in their effects when applied at the same dose rate, with the responses being forage-specific. For RS, the EPX derived fromA. oryzaeshowed the greatest positive effects on forage degradation; whereas for MS and GM, the source of micro-organism where EPX gene was derived did not affect the degradation, with little difference among the EPX evaluated.
Impact of the cestodeTriaenophorus nodulosuson the exoticLepomis gibbosusand the autochthonousPerca fluviatilis
Authors: MASSON G. , VANACKER M. , FOX M. G. , BEISEL J.-N. 
Published: December 2014

SUMMARYThe effects of plerocercoids of the cestodeTriaenophorus nodulosusinfecting the livers of native Eurasian perchPerca fluviatilisand non-native pumpkinseedLepomis gibbosuswas investigated in 17 sites along the Moselle watershed. With a single exception, infected individuals were not observed in the main channel whether or not northern pikeEsox lucius, a final host, was present. In ponds where the pike was present, the prevalence ofT. nodulosusaveraged 86% in Eurasian perch and 15% in pumpkinseed. The parasite was not present at all in ponds when pike were absent. Parasite load, hepatosomatic index (HSI), gonadosomatic index (GSI) and body condition index (CI) were compared between hosts in one site where parasite prevalence and fish abundance was highest. HSI in infected perch was significantly higher than in uninfected perch, whereas no differences in HSI were detected between infected and uninfected pumpkinseed. While perch were more frequently infected and had a greater average parasite load than pumpkinseed, there were no significant differences in either indicator between the two species. Furthermore, no significant differences in GSI or CI were observed between infected and uninfected fish in either species, by either gender or maturity stage. We hypothesize that pumpkinseed is more resistant to the parasite or less likely to feed upon infected copepods than perch.