bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve
Authors: Freysoldt A , Fleckenstein J , Lang PM , Irnich D , Grafe P , Carr RW 
Published: August 2009

Background and purpose: Amitriptyline is often prescribed as a first‐line treatment for neuropathic pain but its precise mode of analgesic action remains uncertain. Amitriptyline is known to inhibit voltage‐dependent ion channels and also to act as an antagonist at ligand‐gated ion channels, such as nicotinic acetylcholine receptors (nAChRs). In the present study, we tested the effect of amitriptyline on nicotinic responses of unmyelinated axons in isolated segments of human peripheral nerve. In particular, a comparison was made between the concentrations of amitriptyline necessary for inhibition of nAChRs and those required for inhibition of the compound C‐fibre action potential.Experimental approach: Isolated axon fascicles were prepared from short segments of human sural nerve, and multiple measures of axonal excitability were recorded using computer‐controlled threshold tracking software.Key results: Amitriptyline (EC502.6 µM) reduced the nicotine‐induced increase in C‐fibre excitability but only slightly altered the amplitude and latency to onset of the compound action potential. In contrast, tetrodotoxin produced a clear reduction in the amplitude and a prolongation of action potential onset latency but was without effect on the nicotine‐induced increase in axonal excitability.Conclusions and implications: These data demonstrate that low concentrations of amitriptyline suppress the response of human peripheral C‐type axons to nicotine by directly inhibiting nAChRs. Blockade of tetrodotoxin‐sensitive, voltage‐dependent sodium channels does not contribute to this effect. An inhibitory action of amitriptyline on nAChRs in unmyelinated nociceptive axons may be an important component of amitriptyline's therapeutic effect in the treatment of neuropathic pain.
Carbon monoxide is a rapid modulator of recombinant and native P2X2ligand‐gated ion channels
Authors: Wilkinson WJ , Gadeberg HC , Harrison AWJ , Allen ND , Riccardi D , Kemp PJ 
Published: August 2009

Background and purpose: Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated.Experimental approach: Whole‐cell patch‐clamp experiments were used to measure ATP‐elicited currents in human embryonic kidney 293 cells heterologously expressing P2X2, P2X3, P2X2/3and P2X4receptors and in rat pheochromocytoma (PC12) cells known to express native P2X2receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM‐2).Key results: CO was a potent and selective modulator of native P2X2receptors, and these effects were mimicked by a CO donor (CORM‐2). Neither pre‐incubation with 8‐bromoguanosine‐3′,5′‐cyclomonophosphate nor 1H‐[1,2,4]Oxadiazolo[4,3‐a]quinoxalin‐1‐one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP‐evoked P2X2currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X2/3and P2X4receptors, but was without effect on P2X3receptors.Conclusions and implications: These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X2receptors in physiological systems.
Methyl ethyl ketone blocks status epilepticus induced by lithium‐pilocarpine in rats
Authors: Inoue Osamu , Sugiyama Eriko , Hasebe Nobuyoshi , Tsuchiya Noriko , Hosoi Rie , Yamaguchi Masatoshi , Abe Kohji , Gee Antony 
Published: August 2009

Background and purpose: A ketogenic diet has been used successfully to treat patients with intractable epilepsy, although the mechanism is unknown. Acetone has been shown to have an anticonvulsive effect in various animal models. The main purpose of this study was to determine whether other ketones, 2‐butanone (methyl ethyl ketone: MEK) and 3‐pentanone (diethyl ketone: DEK), also show anticonvulsive effects in lithium‐pilocarpine (Li‐pilocarpine)‐induced status epilepticus (SE) in rats.Experimental approach: Anticonvulsive effects of MEK and DEK in Li‐pilocarpine SE rats were measured by behavioural scoring. Anti‐seizure effects of MEK were also evaluated using electroencephalography (EEG). Neuroprotective effect of MEK was investigated by haematoxylin and eosin staining 4 weeks after the treatment with pilocarpine.Key results: Acetone, MEK and DEK showed anticonvulsant effects in Li‐pilocarpine‐induced SE rats. Treatment with MEK twice (8 mmol·kg−1and 5 mmol·kg−1) almost completely blocked spontaneous recurrent cortical seizure EEG up to 4 weeks after the administration of pilocarpine. MEK also showed strong neuroprotective effects in Li‐pilocarpine‐treated rats 4 weeks following the administration of pilocarpine. Significant neural cell death occurred in the hippocampus of Li‐pilocarpine SE rats, especially in the CA1 and CA3 subfields. In contrast, normal histological characteristics were observed in these regions in the MEK‐pretreated rats.Conclusions and implications: Both MEK and DEK showed strong anticonvulsive effects in Li‐pilocarpine‐induced SE rats. They also inhibited continuous recurrent seizure and neural damage in hippocampal region for 4 weeks after the treatment with pilocarpine. These findings appear to be of value in the investigation of epilepsy.
Prospective randomised multicentre trial with the birth trainer EPI‐NO® for the prevention of perineal trauma
Authors: RUCKHÄBERLE Eugen , JUNDT Katharina , BÄUERLE Martin , BRISCH Karl‐Heinz , ULM Kurt , DANNECKER Christian , SCHNEIDER Karl Theo Mario 
Published: August 2009

Background: In several non‐randomised trials training with EPI‐NO® increased the rate of intact perineum and decreased episiotomy rates, shortened the second stage of labour and lowered use of pain killers.Aims: To verify the preliminary results with EPI‐NO® in a prospective randomised trial.Methods: Randomised, single‐blind multicentre trial in four university hospitals in Germany including 276 primigravidae.Results: After training with EPI‐NO® we observed a significant increase in the incidence of intact perineum (37.4% vs 25.7%; P = 0.05) and a tendency towards lower episiotomy rates (41.9% vs 50.5%; P = 0.11). We found no significant differences between the two groups regarding incidence of perineal tears, duration of second stage of labour, use of pain relief and rate of vaginal infection.Conclusions: Training with EPI‐NO® increases significantly the likelihood of having an intact perineum and reduces the episiotomy rate.
Migralepsy: A call for a revision of the definition
Authors: Sances Grazia , Guaschino Elena , Perucca Piero , Allena Marta , Ghiotto Natascia , Manni Raffaele 
Published: August 2009

SummaryMigralepsy is an ill‐defined nosologic entity, with only a few cases described in the literature. In the 2004 International Classification for Headache Disorders (ICHD‐II), the International Headache Society proposed that the following diagnostic criteria should be met: (1) migraine fulfilling criteria for 1.2 Migraine with aura (MA) and (2) a seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within 1 h after a migraine aura. Herein, by presenting a case with symptoms suggestive of migralepsy and by reviewing all previous cases described in the literature, we discuss the challenges of differentiating this condition from epileptic seizures, as well as the inaccuracy of the current ICHD‐II definition.
A prospective study of smoking, caffeine, and alcohol as risk factors for seizures or epilepsy in young adult women: Data from the Nurses’ Health Study II
Authors: Dworetzky Barbara A. , Bromfield Edward B. , Townsend Mary K. , Kang Jae H. 
Published: August 2009

SummaryPurpose:  Seizures and epilepsy are associated with significant disability and substantial treatment costs, yet little is known about primary prevention. We prospectively examined the association of cigarette smoking, caffeine use, and alcohol intake with risk of seizure or epilepsy among women, aged 25–42 years, in the Nurses’ Health Study II.Methods:  Participants provided dietary and cigarette smoking information on multiple questionnaires beginning in 1989. Among 116,363 women at‐risk for incident seizure or epilepsy, we confirmed 95 cases of seizure and 151 cases of epilepsy occurring from 1989–2005 using information from a detailed supplementary questionnaire and medical records. Multivariable‐adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression.Results:  Compared with never smoking, current cigarette smoking was associated with an increased risk of seizure (RR 2.60, 95% CI 1.53–4.42), after adjustment for stroke and other potential confounding factors. Past smoking was not associated with risk of seizure, but was associated with modestly increased risk of epilepsy (RR 1.46, 95% CI 1.01–2.12). Long‐term caffeine and moderate alcohol intake were not associated with seizure or epilepsy.Discussion:  Cigarette smoking may be associated with increased risk of seizure. More prospective studies are needed to investigate potential factors to ultimately prevent the development of seizures or epilepsy.
Coactivation of GABA receptors inhibits the JNK3 apoptotic pathway via disassembly of GluR6‐PSD‐95‐MLK3 signaling module in KA‐induced seizure
Authors: Li Chong , Xu Bo , Wang Wei‐Wei , Yu Xiu‐Ju , Zhu Jie , Yu Hong‐Min , Han Dong , Pei Dong‐Sheng , Zhang Guang‐Yi 
Published: August 2009

SummaryPurpose: Past work has demonstrated that kainic acid (KA)–induced seizures could cause the enhancement of excitation and lead to neuronal death in rat hippocampus. To counteract such an imbalance between excitation and inhibition, we designed experiments by activating the inhibitory γ‐aminobutyric acid (GABA) receptor to investigate whether such activation suppresses the excitatory glutamate signaling induced by KA and to elucidate the underlying molecular mechanisms.Methods: Muscimol coapplied with baclofen was intraperitoneally administrated to the rats 40 min before KA injection by intracerebroventricular infusion. Subsequently we used a series of methods including immunoprecipitation, immunoblotting, histologic analysis, and immunohistochemistry to analyze the interaction, expression, and phosphorylation of relevant proteins as well as the survival of the CA1/CA3 pyramidal neurons.Results: Coadministration of muscimol and baclofen exerted neuroprotection against neuron death induced by KA; inhibited the increased assembly of the GluR6‐PSD‐95‐MLK3 module induced by KA; and suppressed the activation of MLK3, MKK7, and JNK3.Discussion: Taken together, we demonstrate that coactivation of the inhibitory GABA receptors can attenuate the excitatory JNK3 apoptotic signaling pathway via inhibiting the increased assembly of the GluR6‐PSD‐95‐MLK3 signaling module induced by KA. This provides a new insight into the therapeutic approach to epileptic seizure.
Validation of a brief screening instrument for the ascertainment of epilepsy
Authors: Ottman Ruth , Barker‐Cummings Christie , Leibson Cynthia L. , Vasoli Vincent M. , Hauser W. Allen , Buchhalter Jeffrey R. 
Published: August 2009

SummaryPurpose:  To validate a brief screening instrument for identifying people with epilepsy in epidemiologic or genetic studies.Methods:  We designed a nine‐question screening instrument for epilepsy and administered it by telephone to individuals with medical record–documented epilepsy (lifetime history of ≥2 unprovoked seizures, n = 168) or isolated unprovoked seizure (n = 54), and individuals who were seizure‐free on medical record review (n = 120), from a population‐based study using Rochester Epidemiology Project resources. Interviewers were blinded to record‐review findings.Results:  Sensitivity (the proportion of individuals who screened positive among affected individuals) was 96% for epilepsy and 87% for isolated unprovoked seizure. The false positive rate (FPR, the proportion who screened positive among seizure‐free individuals) was 7%. The estimated positive predictive value (PPV) for epilepsy was 23%, assuming a lifetime prevalence of 2% in the population. Use of only a single question asking whether the subject had ever had epilepsy or a seizure disorder resulted in sensitivity 76%, FPR 0.8%, and estimated PPV 66%. Subjects with epilepsy were more likely to screen positive with this question if they were diagnosed after 1964 or continued to have seizures for at least 5 years after diagnosis.Discussion:  Given its high sensitivity, our instrument may be useful for the first stage of screening for epilepsy; however, the PPV of 23% suggests that only about one in four screen‐positive individuals will be truly affected. Screening with a single question asking about epilepsy yields a higher PPV but lower sensitivity, and screen‐positive subjects may be biased toward more severe epilepsy.
Hyperpolarization‐activated cation currents in human epileptogenic neocortex
Authors: Wierschke Stephan , Lehmann Thomas‐Nicolas , Dehnicke Christoph , Horn Peter , Nitsch Robert , Deisz Rudolf A. 
Published: August 2009

SummaryPurpose:  Hyperpolarization‐activated cation currents (IH) play a pivotal role in the control of neuronal excitability. In animal models of epilepsy both increases and decreases of IH have been reported. We, therefore, characterized properties of IH in human epileptogenic neocortex.Methods:  Layer II/III neurons in slices from epilepsy surgery tissues and rat cortex were investigated with whole‐cell patch‐clamp recordings.Results:  A total of 484 neurons from 96 temporal lobe epilepsy (TLE) tissues and 32 neurons from 8 frontal lobe epilepsy (FLE) tissues were recorded. Voltage‐clamp recordings revealed on hyperpolarizing command steps two time‐ and voltage‐dependent inward currents, namely a fast, Ba2+‐sensitive current (KIR) and a slowly activating current, namely consisting of two kinetically distinct components sensitive to the established IH blocker ZD7288. Only, the fast component (IH(fast)) of TLE neurons was on average smaller and activated more slowly (density 2.7 ± 1.6 pA/pF; tau 38.4 ± 34.0 ms) than in FLE neurons (4.7 ± 2.3 pA/pF; 16.6 ± 7.9 ms; p < 0.001 for both). Within the TLE tissues the IH(fast) density (averaged per patient) was smaller in cases with numerous annual grand mal seizures (GM; 2.2 ± 0.6 pA/pF) compared to those with few GM (2.8 ± 1.0 pA/pF; p = 0.0184). A similar difference was obtained in the case of complex partial seizures (CPS; many CPS 2.2 ± 0.6 pA/pF; few CPS 2.9 ± 1.0 pA/pF, p = 0.0037).Discussion:  The biophysical properties of IH in cortices from TLE, FLE, and rat tissue suggest a deficit of HCN1 subunits in the human epileptogenic neocortex, which in turn may increase excitability and probability of seizure activity.
Diversity and Connectance in an Industrial Context
Authors: Wright Ramsey A. , Côté Raymond P. , Duffy Jack , Brazner John 
Published: August 2009

SummaryThe ecological metaphor of industrial ecology is a proven conceptual tool, having spawned an entire field of interdisciplinary research that explores the intimate linkages between industry and its underlying natural systems. Besides its name and a number of borrowed concepts, however, industrial ecology has no formal relationship with the ecological sciences. This study explores the potential for further interdisciplinary collaboration by testing whether some of the same quantitative analysis techniques used in community ecology research can have meaning in an industrial context. Specifically, we applied the ecological concepts of connectance and diversity to an analysis of Burnside Industrial Park in Halifax, Nova Scotia. Our results demonstrate that these ecological tools show promise for use in industrial ecology. We discuss the meaning of connectance and diversity concepts in an industrial context and suggest next steps for future studies. We hope that this research will help to lay the groundwork of an ecologically inspired tool kit for analyzing industrial ecosystems.
Transesophageal Electrophysiologic Study to Determine the Inducibility After Successful Ablation of Supraventricular Tachycardia in Children
Authors: ERDOĞAN İLKAY , ÖZER SEMA , KARAGÖZ TEVFIK , ÇELIKER ALPAY 
Published: August 2009

Background: Radiofrequency ablation has become first‐line therapy for supraventricular tachycardia in all age groups, but there has been a concern regarding the long‐term effectiveness of the procedure in children. This study aimed to determine the inducibility after successful ablation of supraventricular tachycardia in children; assessment was performed using a transesophageal electrophysiologic study.
Results: A total of 63 patients who had been treated successfully for supraventricular tachycardia with radiofrequency ablation were included in the study. A transesophageal electrophysiologic study was performed 2 months after radiofrequency ablation. Tachycardia was induced in nine of 34 symptomatic and five of 29 asymptomatic patients by a transesophageal electrophysiologic study. Ten patients had recurrence of the same type of supraventricular tachycardia seen previously, and two had a new type of arrhythmia during a transesophageal electrophysiologic study. Tachycardia inducibility rate was 16% in all patients, 22.8% in patients with atrioventricular reentrant tachycardia, and 8% in patients with atrioventricular nodal reentrant tachycardia.
Conclusion: Radiofrequency ablation is a safe and effective method to manage children with supraventricular tachycardia, but patients must be observed for recurrence and new arrhythmias. Sustained tachycardia may also be induced in asymptomatic patients. A transesophageal electrophysiologic study is effective and safe for follow‐up of radiofrequency ablation for assessment, diagnosis, and treatment of patients.
The economic and poverty impacts of maize research in West and Central Africa
Authors: Alene Arega D. , Menkir Abebe , Ajala S. O. , Badu‐Apraku B. , Olanrewaju A. S. , Manyong V. M. , Ndiaye Abdou 
Published: August 2009

AbstractThis article assembles the results of three multicountry surveys on variety performance and adoption patterns to measure the impacts of maize research in West and Central Africa from 1981 to 2005, and uses cost data since 1971 to compute social rates of return on public investments in maize research in the region. Adoption of modern varieties increased from less than 5% of the maize area in the 1970s to about 60% in 2005, yielding an aggregate rate of return on research and development (R&D) investment of 43%. The estimated number of people moved out of poverty through adoption of new maize varieties rose gradually in the 1980s to more than one million people per year since the mid 1990s. Over half of these impacts can be attributed to international maize research at IITA and CIMMYT. The article concludes with a discussion of strategic options to enhance the impacts of maize research in the region.
Neuronal apoptosis by prolyl hydroxylation: implication in nervous system tumours and the Warburg conundrum
Authors: Schlisio Susanne 
Published: August 2009

AbstractIntroductionLessons from a rare diseaseSpecificity of function within the EglN prolyl hydroxylasesFailure of EglN3‐mediated apoptosis in the genesis of phaeochromocytomaUnderstanding the mechanistic basis of EglN3 killingConnecting EglN activity to the Warburg conundrumFuture directionsOxygen‐sensing mechanisms are often dysfunctional in tumours. Oxygen sensing is mediated partlyviaprolyl hydroxylation. The EglN prolyl hydroxylases are well characterized in regulating the hypoxia inducible factor α (HIF‐α) hypoxic response, but also are implicated in HIF‐independent processes. EglN3 executes apoptosis in neural precursors during development and failure of EglN3 developmental apoptosis can lead to certain forms of sympathetic nervous system tumours. Mutations in metabolic/mitochondrial enzymes (SDH,FH,IDH) impair EglN activity and predisposes to certain cancers. This is because the EglNs not only require molecular oxygen to execute hydroxylation, but also equally require the electron donor α‐ketoglutarate, a metabolite from the Krebs cycle. Therefore EglN enzymes are considered oxygen, and also, metabolic sensors. α‐Ketoglutarate is crucial for EglN hydroxylation activity, whereas the metabolites succinate and fumarate are inhibitors of the EglN enzymes. Since EglN activity is dependent upon metabolites that take part in the Krebs cycle, these enzymes are directly tied into the cellular metabolic network. Cancer cells tend to convert most glucose to lactate regardless of whether oxygen is present (aerobic glycolysis), an observation that was first made by Otto Warburg in 1924. Despite the striking difference in ATP production, cancer cells might favour aerobic glycolysis to escape from EglN hydroxylation, resulting in the accumulation of oncogenic HIFα and/or resistance to EglN3‐mediated apoptosis.
Social anxiety disorder: what are we losing with the current diagnostic criteria?
Authors: Filho A. S. , Hetem L. A. B. , Ferrari M. C. F. , Trzesniak C. , Martín‐Santos R. , Borduqui T. , De Lima Osório F. , Loureiro S. R. , Busatto Filho G. , Zuardi A. W. , Crippa J. A. S. 
Published: August 2009

Filho AS, Hetem LAB, Ferrari MCF, Trzesniak C, Martín‐Santos R, Borduqui T, de Lima Osório F, Loureiro SR, Busatto Filho G, Zuardi AW, Crippa JAS. Social anxiety disorder: what are we losing with the current diagnostic criteria?Objective:  To assess the rate of comorbidities and the functional impairment associated with the social anxiety disorder (SAD), with an emphasis on the so‐called subthreshold clinical signs and symptoms.Method:  Psychiatric comorbidities and psychosocial functioning were evaluated in 355 volunteers (college students) who had been diagnosed as SAD (n = 141), Subthreshold SAD (n = 92) or Controls (n = 122).Results:  The rate of comorbidities was 71.6% in the SAD group and 50% in subjects with Subthreshold SAD, both significantly greater than Controls (28.7%). Concerning psychosocial functioning, the SAD group had higher impairment than the other two groups in all domains evaluated, and subjects with Subthreshold SAD presented intermediate values.Conclusion:  The rates of psychiatric comorbidities and the impairment of psychosocial functioning increase progressively along the spectrum of social anxiety. The fact that Subthreshold SAD causes considerable disability and suffering in comparison with control subjects justifies a review of the validity of the diagnostic criteria.