bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topiramate reduces AMPA‐induced Ca2+ transients and inhibits GluR1 subunit phosphorylation in astrocytes from primary cultures
Authors: Ängehagen Mikael , Rönnbäck Lars , Hansson Elisabeth , Ben‐Menachem Elinor 
Published: July 2005

AbstractTopiramate (TPM) is a structurally novel broad spectrum anticonvulsant known to have a negative modulatory effect on the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)/kainate subtypes of glutamate receptors and some types of voltage‐gated Na+ and Ca2+ channels, and a positive modulatory effect on some types of γ‐aminobutyric acidA (GABAA) receptors and at least one type of K+ channels in neurons. In an earlier work, we showed that the negative modulatory effect of TPM (100 μm) on AMPA/kainate receptors in neurons is dependent on TPM modulation of the phosphorylation state of these receptors. In this work, we investigated the effect of TPM on AMPA‐induced intracellular calcium ([Ca2+]i) responses in cultured rat cortical astrocytes, with special interest in intracellular mechanisms. Here, we report that the ability of TPM (1–100 μm) to inhibit AMPA‐induced accumulation of Ca2+ in astrocytes is inversely related to the level of protein kinase A (PKA) ‐mediated phosphorylation of channels activated by AMPA. The level of receptor phosphorylation was further determined with western blot using phosphorylation specific antibodies that recognize the glutamate receptor 1 (GluR1) subunit phosphorylated on Ser845. These results demonstrated that, even in cultured cortical astrocytes, TPM significantly reduced the phophorylation level of GluR1 subunits. Furthermore, it was shown that TPM binds to AMPA receptors in the dephosphorylated state and thereby exerts an allosteric modulatory effect on the ion channel.
Insulin modulates hippocampal activity‐dependent synaptic plasticity in a N‐methyl‐d‐aspartate receptor and phosphatidyl‐inositol‐3‐kinase‐dependent manner
Authors: Van Der Heide Lars P. , Kamal Amer , Artola Alain , Gispen Willem Hendrik , Ramakers Geert M. J. 
Published: July 2005

AbstractInsulin and its receptor are both present in the central nervous system and are implicated in neuronal survival and hippocampal synaptic plasticity. Here we show that insulin activates phosphatidylinositol 3‐kinase (PI3K) and protein kinase B (PKB), and results in an induction of long‐term depression (LTD) in hippocampal CA1 neurones. Evaluation of the frequency–response curve of synaptic plasticity revealed that insulin induced LTD at 0.033 Hz and LTP at 10 Hz, whereas in the absence of insulin, 1 Hz induced LTD and 100 Hz induced LTP. LTD induction in the presence of insulin required low frequency synaptic stimulation (0.033 Hz) and blockade of GABAergic transmission. The LTD or LTP induced in the presence of insulin was N‐methyl‐d‐aspartate (NMDA) receptor specific as it could be inhibited by α‐amino‐5‐phosphonopentanoic acid (APV), a specific NMDA receptor antagonist. LTD induction was also facilitated by lowering the extracellular Mg2+ concentration, indicating an involvement of NMDA receptors. Inhibition of PI3K signalling or discontinuing synaptic stimulation also prevented this LTD. These results show that insulin modulates activity‐dependent synaptic plasticity, which requires activation of NMDA receptors and the PI3K pathway. The results obtained provide a mechanistic link between insulin and synaptic plasticity, and explain how insulin functions as a neuromodulator.
Aging of hair
Authors: Trüeb Ralph M 
Published: August 2005

SummaryThe appearance of hair plays an important role in people's overall physical appearance and self‐perception. With today's increasing life expectation, the desire to look youthful plays a bigger role than ever. The hair care industry has become aware of this and also more capable to deliver active products that are directed toward meeting this consumer demand. The discovery of pharmacological targets and the development of safe and effective drugs also indicate strategies of the drug industry for maintenance of healthy and beautiful hair. Hair aging comprises weathering of the hair shaft and aging of the hair follicle. The latter manifests as decrease of melanocyte function or graying, and decrease in hair production in androgenetic and senescent alopecia. The scalp is also subject to intrinsic or physiologic aging and extrinsic aging caused by external factors. Intrinsic factors are related to individual genetic and epigenetic mechanisms with interindividual variation. Prototypes are familial premature graying and androgenetic alopecia. Extrinsic factors include ultraviolet radiation and smoking. Experimental evidence supports the hypothesis that oxidative stress plays a role in skin and hair aging. Topical anti‐aging compounds for hair include humefactants, hair conditioners, photoprotectors, and antioxidants. Current available treatment modalities with proven efficacy for treatment of androgenetic alopecia are topical minoxidil, oral finasteride, and autologous hair transplantation. In the absence of another way to reverse hair graying, hair colorants are the mainstays of recovering lost hair color. Topical liposome targeting for melanins, genes, and proteins selectively to hair follicles are under current investigation.
Comparative Tolerability of Oral 5‐HT1B/1D Agonists
Authors: Fox Anthony W. , Ffpm  
Published: July 2005

Objectives.—To compare the relative tolerability of 5‐HT1B/1D agonists and to investigate the relationships (if any) among systemic exposure, lipophilicity, and clinical tolerability for 5‐HT1B/1D agonists.Methods.—Post hoc correlations were sought among the following variables: absolute dose (=administered dose × oralbioavailability), Cmax, LogDpH7.4 (LogD), frequencies of all, neurological and dizziness/somnolence/drowsiness adverse events, adjusted for corresponding placebo‐associated frequencies.Results.—For effective doses of all drugs with available data, absolute dose‐response relationships exist for adverse event frequencies. The overall rank order of the frequency of adverse events was as follows: naratriptan < sumatriptan = rizatriptan < zolmitriptan.With the exception of eletriptan, 5‐HT1B/1D agonists exhibit correlations between absolute dose, Cmax (R = 0.97), and LogD (R = 0.71). For neurological and dizziness/somnolence/drowsiness adverse event frequencies, the overall rank order was sumatriptan < naratriptan < rizatriptan < zolmitriptan. Neither LogD nor absolute dose size predicted adverse event frequencies.Conclusions.—Triptans may be distinguished in terms of their tolerability. Effectiveness, absolute dose size, and lipophilicity are related for the 5‐HT1B/1Dagonists considered here, except eletriptan. Adverse event frequencies cannot be predicted from in vitro measures of lipophilicity, in vivo estimates of absolute bioavailability, dose size, or any combination of these variables. Since these drugs are all agonists at 5‐HT1B/1D receptors in the low nanomolar range, but differ in their tolerability profiles, adverse effects are not likely to be mediated through 5‐HT1B/1D receptors. Drugs of this class must be studied individually and on a reasonably large scale in clinical development programs.
Burst Suppression and Impairment of Neocortical Ontogenesis: Electroclinical and Neuropathologic Findings in Two Infants with Early Myoclonic Encephalopathy
Authors: Spreafico R. , Angelini L. , Binelli S. , Granata T. , Rumi V. , Rosti D. , Runza L. , Bugiani O. 
Published: August 2005

Summary:We report the electroclinical and neuropathologic correlations in 2 children aged 2.5 months affected by early myoclonic encephalopathy characterized by epileptic seizures, erratic myoclonus, and an EEG pattern of burst suppression. Despite different etiologies, the neuropathologic findings showed similar abnormalities in both cases, with no substantial impairment of the myelination processes. Islands of matrix tissue scattered in the periventricular region and neurons aligned marginally in the bulbar olives were detected. The presence of numerous large spiny neurons dispersed in the white matter along the axons of the cortical gyri was the most striking finding. These neurons have been interpreted as abnormally persisting interstitial cells in 2.5‐month‐old children. These early generated neurons, normally present during neocortical histogenesis, are programmed to die near the end of gestation or soon after birth. The interstitial cells are regarded as a waiting compartment of afferent fibers during cortical development. Their persistence in our patients represents an anatomic condition for cortical disconnection providing a pathophysiologic basis to burst‐suppression phenomena.
Usefulness of Unilateral Interictal Sharp Waves of Temporal Lobe Origin in Prolonged Video‐EEG Monitoring Studies
Authors: Kanner Andres M. , Morris Harold H. , Lüders Hans , Dinner Dudley S. , Van Ness Paul , Wyllie Elaine 
Published: August 2005

Summary:The value of EEG interictal epileptiform activity in predicting location of the seizure focus remains controversial. In 64 patients, scalp video‐EEG monitoring studies showed one or two ipsilateral interictal foci in the temporal lobe. The site of these interictal foci correlated with location of the seizure focus recorded during prolonged video‐electrocorticography (ECoG) with use of subdural grids placed under the mesiobasal temporal region and over the lateral temporal convexity. Our findings suggest that unilateral anterotemporal interictal foci can accurately predict location of seizure onset. This is also true in patients with two ipsilateral temporal interictal foci, provided that the dominant focus is localized in anterotemporal regions. We believe that in such patients invasive recordings are not warranted, but we caution against sole use of interictal epileptiform criteria for localization of the seizure focus. Correlation with clinical information, ictal EEG, neuropsychometric, and neu‐roimaging studies is required before performance of epilepsy surgery.
Adjuvant Vigabatrin in Refractory Epilepsy: A Ceiling to Effective Dosage in Individual Patients?
Authors: McKee P. J. W. , Blacklaw J. , Friel E. , Thompson G. G. , Gillham R. A. , Brodie M. J. 
Published: August 2005

Summary:A double‐blind, randomized, cross‐over study of additional vigabatrin (γ‐vinyl‐GABA, VGB, 1.0 g twice daily for 6 weeks, followed by 1.5 g twice daily for 6 weeks) and matched placebo was undertaken in 24 patients with refractory epilepsy. Nineteen completed the trial satisfactorily. Fewer seizure days were reported during VGB treatment [placebo 41, VGB 23, p < 0.05, 95% confidence interval (CI) −1.5 to −14]. An overall reduction in median seizure numbers failed to reach statistical significance (n = 19; placebo 52, VGB 32, NS, 95% CI −18 to + 24). Subgroup analysis, however, showed a significant reduction in partial seizures (n = 17) with 2 g VGB daily (placebo 22, VGB 13, p < 0.05, 95% CI −0.5 to −16.5), but not with higher dosage (placebo 28, VGB 22, NS, 95% CI − 18 to + 11). A deterioration in control of partial seizures as compared with the equivalent placebo phase was observed when patients were changed from 2 to 3 g/day VGB (2 g VGB 13, 3 g VGB 22, p = 0.05, 95% CI 0 to +20). Loss of efficacy was noted in 3 patients, and seizure control worsened slightly in 5 others. One previously resistant patient developed a therapeutic response, and 2 other patients reported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to benefit tonic‐clonic seizures. Serum VGB concentrations were higher during treatment with 3 g (15.5 ± 8.9 mg/L) daily than with 2 g (13.5 ± 11.2 mg/L). No important alterations were noted in the concentrations of concomitantly administered antiepileptic drugs (AEDs) throughout the trial. VGB is useful adjuvant therapy for treatment of partial seizures. There may be a ceiling to effective dosage. This demands individual dose titration for each patient.
Partial Epilepsy of Long Duration: Changing Semiology with Age
Authors: Tinuper Paolo , Provini Federica , Marini Carla , Cerullo Angelina , Plazzi Giuseppe , Avoni Patrizia , Baruzzi Agostino 
Published: August 2005

Summary:There are few data on changing patterns of localization‐related epileptic syndromes with time and particularly on changes in seizure semiology as patients age. We retrospectively reviewed 53 patients aged >60 years who had had partial epileptic seizures for a mean duration of 44 years. In 20 patients, seizures became progressively less elaborate and briefer with time. In 29 patients, seizures were unchanged. In four patients, seizures worsened, with the appearance of drop attacks, secondarily generalized seizures, increasing drug resistance, and mental deterioration. These latter 4 patients had cerebrovascular disease with multiple strokes.
Felbamate Levels in Patients with Epilepsy
Authors: Harden Cynthia L. , Trifiletti Rosario , Kutt Henn 
Published: August 2005

Summary:The usefulness of felbamate (FBM) levels in managing epilepsy patients has not been determined. The purpose of the present study was to determine if FBM levels obtained at routine office visits correlated with side effects reported by patients. We determined FBM levels by high‐pressure liquid chromatography (HPLC) of 46 epilepsy patient plasma specimens (41 patients) and assessed medication toxicity and seizure frequency by a questionnaire. Thirty‐six patients were treated with other antiepileptic drugs (AEDs); concomitant AED levels not in ranges believed to cause toxicity. FBM levels ranged from 9 to 134 pg/ml, and were divided into three groups for analysis, resulting in low‐range (9–36 pg/ml), mid‐range (37–54 μg/ml), and high‐level (44–134 pg/ml) groups. Anorexia and complaints of severe side effects were reported significantly more often in the high‐level group as compared with the low‐ and midrange groups. Significantly more patients in the high‐level group (1043) reported decreased seizure frequency, as compared with 12 of 30 of patients in the low‐and midrange groups combined. FBM levels correlated linearly with doses overall, but most closely in FBM monotherapy patients.
Cryptogenic Partial Epilepsies with Anti‐GM1 Antibodies: A New Form of Immune‐Mediated Epilepsy?
Authors: Bartolomei Fabrice , Boucraut José , Barrié Maryline , Kok Jérome , Dravet Charlotte , Viallat Danièle , Bernard Dominique , Gastaut Jean‐Louis 
Published: August 2005

Summary: Purpose: We wished to study immune system dysfunction which has been proposed as a potential cause of epilepsy. Epileptogenic action of antibodies directed against GM1 gangliosides was demonstrated in rats, but the potential role of anti‐GMI antibodies in human epilepsy has not yet been studied. Methods: We investigated the presence of IgG or IgM anti‐GMI antibodies in the sera of 64 patients with various types of epileptic syndromes: idiopathic generalized epilepsy (ICE) (n = 6), symptomatic or cryptogenic generalized epilepsy (SCGE) (n = 7), symptomatic partial epilepsy (SPE) (n = 26), and cryptogenic partial epilepsy (CPE) (n = 25). Results: Two patients had elevated titers of IgM anti‐ GMl antibodies, one patient had elevated titers of both IgM and IgG anti‐GM1 antibodies, and I patient had elevated titers of IgG anti‐GMI antibodies. All 4 patients had complex partial seizures (CPS) secondarily generalized, generalized, drug resistance, psychiatric disorders, and normal brain imaging. Anti‐GMI antibodies were never associated with ICE, SCGE, or SPE. We compared the reactivity of sera from these patients with the sera from 5 patients with motor neuropathies with conduction block (MNCB) against different gangliosides and concluded that epilepsy sera did not react with the Gal(β1‐3)GalNAc epitope. Two anti‐GM1‐positive patients were treated successfully with high‐dose intravenous immunoglobulins (IgIV). Conclusions: Our findings suggest that detection of anti‐GM1 antibodies could allow identification of a subgroup of patients with partial epilepsy associated with an autoimmune response. If anti‐GM1 antibodies prove pathogenic, they could be an important prognostic factor for drug resistance and worsening of seizures.
Postictal Language Dysfunction in Patients with Right or Bilateral Hemispheric Language Localization
Authors: Privitera Michael , Kohler Christian , Cahill William , Yeh Hwa‐Shain 
Published: August 2005

Summary: Purpose: As shown previously, when temporal lobe complex partial seizures (TLCPS) originate from the language dominant hemisphere, patients cannot read a test phrase correctly within 60 s of the end of the ictal discharge. We wished to assess whether postictal language testing results discordant with this pattern identified patients with non‐left (right hemisphere or mixed) language dominance. Methods: Since 1988, all patients undergoing video/EEG monitoring at our institution have been given a test phrase to read aloud as soon as a seizure is detected. Inclusion criteria for this study were (a) postictal language testing within 60 s of seizure end for at least one TLCPS, (b) >90% seizure reduction after anterior temporal lobectomy with 2‐year minimum follow‐ follow‐ up, and (c) language localization by either intracarotid amobarbital test (IAT) or direct electrical stimulation of left hemisphere cortex. Results: Two hundred twenty‐four seizures in 64 patients were analyzed. Discordant postictal language patterns were noted in 10 of 11 patients with IAT documented non‐left language dominance and in 15 of 53 with left dominance (p = 0.006; sensitivity 90.9%, specificity 71.7%). Conclusions: Postictal language testing accurately identifies patients with non‐left language dominance and may be useful in selecting appropriate patients for IAT.
Influence of Epilepsy on Mortality in Mental Retardation: An Epidemiologic Study
Authors: Forsgren Lars , Edvinsson Sven‐Olov , Nyström Lennarth , Blomquist Hans Kson 
Published: August 2005

Summary: Purpose: A cohort consisting of all persons with known mental retardation (MR) and living in a Swedish province on December 31, 1985, was followed for 7 years (1987–1992) to study the mortality pattern. Methods: A file of the cohort was linked to the cause‐of‐death pattern of the general population in the study area. Results: One hundred twenty‐four deaths (8.4%) occurred among the 1,478 persons with MR. Thirty deaths (10.1%) occurred among the 296 persons with epilepsy and MR. The standardized mortality ratio (SMR) in those with only MR was significantly increased as compared with that of the general population: 1.6 [95% confidence interval (CI) 1.3–2.01; MR and epilepsy, 5.0 (CI 3.3–7.5); and MR, epilepsy, and cerebral palsy (CP), 5.8 (CI 3.4–9.7). Mortality was increased both in patients with partial seizures without seizures secondarily generalized (SMR 3.7, CI 1.0–13.6) and in patients with seizures secondarily generalized (5.0, CI 2.3–11.0). The highest mortality occurred in patients who had seizures that were always generalized from the onset: 8.1 (CI 5.7–11.5). Mortality increased with increasing seizure frequency during the year preceding the prevalence date. In patients with epilepsy and MR, pneumonia was the most common cause of death and a seizure was the probable cause of death in 6.7%. Conclusions: Epilepsy is associated with a significantly increased mortality in persons with MR. The increase is related to seizure type and seizure frequency. Death in persons with epilepsy and MR is seldom directly due to seizures. Other impairments associated with epilepsy and MR are important causes of death.
Infant Monkey Hyperexcitability After Prenatal Exposure to Antiepileptic Compounds
Authors: Phillips Nona K. , Lockard Joan S. 
Published: August 2005

Summary: Purpose: A monkey (Macaca fascicularis) model was previously used to assess infant hyperexcitability after prenatal exposure to phenytoin (PHT), stir‐ipentol (STP) or PHT + STP. To explore this issue further, we studied additional monkey infants in those groups, as well as groups prenatally exposed to carba‐mazepine (CBZ) in monotherapy (n = 5) or CBZ + STP poly therapy (n = 10). Methods: The drug‐exposed groups were compared with a group of control infants (n = 10) for whom procedures were matched except that there was no prenatal drug exposure. All adult female monkeys were equipped with tether systems and stomach catheters so that drug administration (or water for controls) could be initiated before they were mated and continued throughout pregnancy. During pregnancy, PHT, STP, and CBZ plasma levels were maintained between 4–12, 4–10, and 1–6 μg/ml, respectively (for both monotherapy and polytherapy). At birth, infants were separated from mothers and transferred to the University of Washington's (Seattle, WA, U.S.A.) Infant Primate Research Laboratory (IPRL) for postnatal care and follow‐up testing. During tests of recognition memory administered between 2 weeks and 3 months of age, infants were rated on a hyperexcitability scale. Results: Previously reported data indicated that infants prenatally exposed to PHT, in monotherapy or polytherapy with STP, were at increased risk for hyperexcitability (screeching, refusing to attend to stimuli, lack of visual orientation). This was not the case for infants prenatally exposed to STP monotherapy. Conclusions: Our results confirm previous findings and also demonstrate that infants prenatally exposed to CBZ or CBZ + STP, like controls, are not hyperexcitable during testing.
Schizencephaly: Neuroradiologic and Epileptologic Findings
Authors: Granata Tiziana , Battaglia Giorgio , D'Incerti Ludovico , Franceschetti Silvana , Spreafico Roberto , Battino Dina , Savoiardo Mario , Avanzini Giuliano 
Published: August 2005

Summary: Purpose: Nine patients affected by schizencephaly were analyzed, and the epileptologic findings prospectively studied, to define the relations between the anatomic brain malformations and clinical outcome. Methods: The schizencephaly was diagnosed by means of magnetic resonance imaging (eight cases) or computed tomography (one case). The clinical histories of all the patients were analyzed, and a psychometric evaluation was made. The electroclinical features and course of epilepsy in the six patients with epilepsy were prospectively followed up for a period ranging from 3 to 14 years. Results: The patients were divided into those who were unilaterally (six) and those bilaterally (three) affected. The former were characterized by mild neurologic deficits and late–onset epilepsy; their epileptologic features were consistent in terms of age of onset, seizure semiology, the absence of secondary generalization, and resistance to antiepileptic treatment. The patients with bilateral schizencephaly associated with other brain malformations were characterized by severe neurologic deficits but were only rarely affected by epilepsy, which was always completely controlled by antiepileptic treatment. Conclusions: Our data show that the extent of anatomic malformation is strictly related to the severity of motor and mental impairment but not to the presence or severity of epilepsy. The absence of prenatal risk factors for brain damage in our series, previously described familial cases of schizencephaly, and the recent report of mutations in homeobox gene EMX2 associated with cases of schizencephaly all indicate that genetic factors may play a key role in the pathogenesis of this brain malformation.