bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natriuretic Peptides and the Dialysis Patient
Authors: Suresh Mathavakkannan , Farrington Ken 
Published: September 2005

ABSTRACTThe natriuretic peptide family consists of four structurally similar, but genetically distinct molecules with pronounced cardiovascular and renal actions. They are counterregulatory hormones playing an important role in fluid volume homeostasis. Atrial natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP) cause diuresis, natriuresis, and vasodilatation. C‐type natriuretic peptide (CNP) has antimitogenic effects and causes vascular smooth muscle relaxation. Dendroaspis natriuretic peptide (DNP) shares many of the actions of ANP and BNP, but its function in humans is not yet fully understood. Natriuretic peptides have been extensively investigated as biochemical markers of the fluid state. Levels are elevated in disease conditions characterized by fluid overload and are closely related to survival in various cardiac disease states. In the dialysis population, BNP correlates significantly with cardiac function, whereas ANP is sensitive to volume changes during dialysis. However, changes in concentration do not predict achievement of euvolemia, and short half‐life, combined with complicated assay techniques, make ANP a less than satisfactory tool for assessing hydration. BNP is a superior prognosticator for risk stratification in dialysis patients, and serial estimations will help in the identification of occult cardiac disease.
Expression of Multidrug Transporters MRP1, MRP2, and BCRP Shortly after Status Epilepticus, during the Latent Period, and in Chronic Epileptic Rats
Authors: Van Vliet Erwin A. , Redeker Sandra , Aronica Eleonora , Edelbroek Peter M. , Gorter Jan A. 
Published: September 2005

Summary:  Purpose: Overexpression of multidrug transporters may play a role in the development of pharmacoresistance by decreasing extracellular drug levels in the brain. However, it is not known whether overexpression is due to an initial insult or evolves more gradually because of recurrent spontaneous seizures. In the present study, we investigated the expression of different multidrug transporters during epileptogenesis in the rat. In addition, we determined whether these transporters affected phenytoin (PHT) distribution in the brain. Methods: Expression of multidrug resistance–associated proteins MRP1 and MRP2 and breast cancer–resistance protein (BCRP) was examined after electrically induced status epilepticus (SE) by immunocytochemistry and Western blot analysis. Brain/blood PHT levels were determined by high‐performance liquid chromatography (HPLC) analysis in the presence and absence of the MRP inhibitor probenecid. Results: Shortly after SE, MRP1, MRP2, and BCRP were upregulated in astrocytes within several limbic structures, including hippocampus. In chronic epileptic rats, these proteins were overexpressed in the parahippocampal cortex, specifically in blood vessels and astrocytes surrounding these vessels. Overexpression was related to the occurrence of SE and was present mainly in rats with a high seizure frequency. Brain PHT levels were significantly lower in epileptic rats compared with control rats, but pharmacologic inhibition of MRPs increased the PHT levels. Conclusions: Overexpression of MRP and BCRP was induced by SE as well as recurrent seizures. Moreover, overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs. These data suggest that administration of antiepileptic drugs in combination with specific inhibitors for multidrug transporters may be a promising therapeutic strategy in pharmacoresistant patients.
Gender Differences in Febrile Seizure–induced Proliferation and Survival in the Rat Dentate Gyrus
Authors: Lemmens Evi M. P. , Lubbers Tim , Schijns Olaf E. M. G. , Beuls Emile A. M. , Hoogland Govert 
Published: September 2005

Summary:  Purpose: Febrile seizures are fever‐associated early‐life seizures that are thought play a role in the development of epilepsy. Seizure‐induced proliferation of dentate granule cells has been demonstrated in several adult animal models and is thought to be an integral part of epileptogenesis. The aim of the present study was to investigate proliferation and survival of dentate gyrus (DG) cells born after early‐life hyperthermia (HT)‐induced seizures in male and female rats. Methods: At postnatal day (PN) 10, male and female rats were exposed to heated air to induce seizures. Littermates were used as normothermia controls. Convulsive behavior was observed by two researchers. From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. The number of BrdU‐immunoreactive cells in the DG was counted at PN17 and PN66. Results: At PN17, male as well as female HT rats had the same amount of BrdU‐positive cells compared with controls. At PN66, significantly more BrdU‐positive cells were left in HT females (53%) than in controls (44%, percentage of BrdU‐positive cells at PN17), whereas no difference was found between HT males and male controls. The net result of proliferation and survival at PN66 was that female HT rats had the same number of BrdU‐immunoreactive cells as controls, whereas male HT rats had 25% more BrdU‐immunoreactive cells than did controls (p < 0.05). Conclusions: Early‐life seizures cause a sexually dimorphic cytogenic response that results in an increased population of newborn DG cells in young adult males, while leaving that of young adult females unaltered.
Quinine, a Blocker of Neuronal Cx36 Channels, Suppresses Seizure Activity in Rat Neocortex In Vivo
Authors: Gajda Zita , Szupera Zoltán , Blazsó Gábor , Szente Magdolna 
Published: September 2005

Summary:  Purpose: The selective contribution of neuronal gap junction (GJ) communication via connexin 36 (Cx36) channels to epileptogenesis and to the maintenance and propagation of seizures was investigated in both the primary focus and the mirror focus by using pharmacologic approaches with the 4‐aminopyridine in vivo epilepsy model. Methods: ECoG recording was performed on anesthetized adult rats, in which either quinine, a selective blocker of Cx36, or the broad‐spectrum GJ blockers carbenoxolone and octanol were applied locally, before the induction or at already active epileptic foci. Results: The blockade of Cx36 channels by quinine before the induction of epileptiform activity slightly reduced the epileptogenesis. When quinine was applied after 25–30 repetitions of seizures, a new discharge pattern appeared with frequencies >15 Hz at the initiation of seizures. In spite of the increased number of seizures, the summated ictal activity decreased, because of the significant reduction in the duration of the seizures. The amplitudes of the seizure discharges of all the patterns decreased, with the exception of those with frequencies of 11–12 Hz. The blockade of Cx36 channels and the global blockade of the GJ channels resulted in qualitatively different modifications in ictogenesis. Conclusions: The blockade of Cx36 channels at the already active epileptic focus has an anticonvulsive effect and modifies the manifestation of the 1‐ to 18‐Hz seizure discharges. Our findings indicate that the GJ communication via Cx36 channels is differently involved in the synchronization of the activities of the networks generating seizure discharges with different frequencies. Additionally, we conclude that both neuronal and glial GJ communication contribute to the manifestation and propagation of seizures in the adult rat neocortex.
Reversible Cytotoxic Edema in the Splenium of the Corpus Callosum Related to Antiepileptic Treatment: Report of Two Cases and Literature Review
Authors: Prilipko Olga , Delavelle Jacqueline , Lazeyras Francois , Seeck Margitta 
Published: September 2005

Summary:  Purpose: Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology. Methods: We report two cases including a 25‐year‐old male patient and a 12‐year‐old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation. Results: Comprehensive MRIs, including diffusion tensor imaging–based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient. Conclusions: On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion.
The Prognostic Value of [18F]FDG‐PET in Nonrefractory Partial Epilepsy
Authors: Weitemeyer Lars , Kellinghaus Christoph , Weckesser Matthias , Matheja Peter , Loddenkemper Tobias , Schuierer Gerhard , Schober Otmar , Ringelstein E. Bernd , Lüdemann Peter 
Published: September 2005

Summary:  Purpose: Regional abnormalities of cerebral glucose metabolism, as identified by 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG‐PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG‐PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease. Methods: We investigated interictal abnormalities of cerebral glucose metabolism by using FDG‐PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after ≥2 years of follow‐up. Results: Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty‐one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow‐up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow‐up period of 43 months. Conclusions: Regional hypometabolism in FDG‐PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.
Subcortical Nuclei Volumetry in Idiopathic Generalized Epilepsy
Authors: Seeck Margitta , Dreifuss Sylvain , Lantz Goran , Jallon Pierre , Foletti Giovanni , Despland Paul‐Andre , Delavelle Jacqueline , Lazeyras Francois 
Published: September 2005

Summary:  Purpose: The exact anatomic and neurophysiologic correlates of idiopathic generalized epilepsy (IGE) in humans are still not well understood, although the thalamus has frequently been invoked as the crucial structure in the generation of primary generalized seizures. The few in vivo magnetic resonance (MR)‐based studies in IGE patients suggest an altered cortical/subcortical gray matter ratio, but with no evidence of structural alterations of the thalamus. In this study, we sought to determine the volumes of the other subcortical structures. Methods: The volumes of the caudate nucleus, putamen, pallidum as well as the thalamus were each determined in both hemispheres in 11 patients with various IGE syndromes, normalized for whole‐brain volumes and then compared with 15 age‐matched controls. Results: No differences were noted in thalamic volumes, confirming previous reports. However, smaller subcortical volumes were noted in the IGE patients (p < 0.009), mainly due to smaller putamen bilaterally (p ≤ 0.015). Conclusions: It is speculated that the presence of discrete frontal dysfunction, as noted in neuropsychological studies in IGE patients, indirectly supports our results because the putamen projects predominantly to the frontal cortex. Larger studies with more homogeneous patient populations are needed to determine the robustness of these findings and whether they are specific for particular IGE syndromes.
Effects of Nefiracetam, a Novel Pyrrolidone‐type Nootropic Agent, on the Amygdala‐kindled Seizures in Rats
Authors: Kitano Yutaka , Komiyama Chika , Makino Mitsuhiro , Kasai Yoshio , Takasuna Kiyoshi , Kinoshita Masakazu , Yamazaki Osamu , Takazawa Akira , Yamauchi Toshio , Sakurada Shinobu 
Published: September 2005

Summary: Purpose:Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition‐enhancing effects. The present study focused on the effects of NEF in amygdala‐kindled seizures and its potential for antiepileptic therapy.Methods:Effects of NEF on fully amygdala‐kindled seizures and development of amygdala‐kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone‐type antiepileptic drug (AED).Results:In fully amygdala‐kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose‐dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala‐kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala‐kindled seizures. As well as fully amygdala‐kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration.Conclusions:Although NEF possesses potent anticonvulsant effects on fully amygdala‐kindled seizures, it has few or no effects on the development of amygdala‐kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala‐kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.
Focal Semiologic and Electroencephalographic Features in Patients with Juvenile Myoclonic Epilepsy
Authors: Usui Naotaka , Kotagal Prakash , Matsumoto Riki , Kellinghaus Christoph , Lüders Hans Otto 
Published: September 2005

Summary:  Purpose: A few reports have described focal electroencephalographic or clinical features or both of juvenile myoclonic epilepsy (JME), but without video‐EEG documentation. We examined focal clinical and EEG features in patients with JME who underwent video‐EEG monitoring. Methods: Twenty‐six patients (nine males and 17 females) who had seizures recorded during video‐EEG monitoring were included. Age at seizure onset was 0 to 22 years (mean, 12.3 years), and age at monitoring was 12 to 44 years (mean, 26.5 years). In one patient with left parietooccipital epilepsy, primary generalized tonic–clonic seizures developed after resection of the parietal tumor. Two patients had both temporal lobe epilepsy and JME. Videotaped seizures in each patient were analyzed. Interictal and ictal EEG also were analyzed for any focal features. Results: Focal semiologic features were observed in 12 (46%) of 26 patients. Six patients had focal myoclonic seizures, and two had Figure 4 sign: one with version to the left, and another had left version followed by Figure 4 sign, and left arm clonic seizure. Their ictal EEGs were generalized at onset but with a lateralized evolution over the right hemisphere. The patient who had both JME and left parietooccipital epilepsy, right arm clonic seizure, and Figure 4 sign was seen during a generalized EEG seizure. Interictally, one patient had temporal sharp waves, and another had run of spikes in the right frontal region. Conclusions: Fourteen (54%) of 26 patients with JME exhibited focal semiologic or electroencephalographic features or both. Video‐EEG was essential in reaching a correct diagnosis and choosing an appropriate antiepileptic drug regimen.
Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation
Authors: Huemer Martina , Ausserer Bernd , Graninger Gunther , Hubmann Michael , Huemer Christian , Schlachter Kurt , Tscharre Arthur , Ulmer Hanno , Simma Burkhard 
Published: September 2005

Summary:  Purpose: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients. Methods: 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3‐month double‐blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo. Results: Hyperhomocysteinemia (tHcy >10.4 μmol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 ± 4 vs. 11.0 ± 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C→T, 1298 A→C, 1793 G→A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group. Conclusions: Hyperhomocysteinemia is present in 15.5% of children receiving long‐term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.
A Pilot Study on Brain‐to‐Plasma Partition of 10,11‐Dyhydro‐10‐hydroxy‐5H‐dibenzo(b,f)azepine‐5‐carboxamide and MDR1 Brain Expression in Epilepsy Patients Not Responding to Oxcarbazepine
Authors: Marchi Nicola , Guiso Giovanna , Rizzi Massimo , Pirker Susanne , Novak Klaus , Czech Thomas , Baumgartner Christoph , Janigro Damir , Caccia Silvio , Vezzani Annamaria 
Published: September 2005

Summary:  Purpose: We measured the brain‐to‐plasma partition of 10,11‐dihydro‐10‐hydroxy‐5H‐dibenzo(b,f)azepine‐5‐carboxamide (10‐OHCBZ) in epilepsy patients undergoing surgery to alleviate drug‐resistant seizures and administered with different oral doses of oxcarbazepine (OXC). We addressed the possible contribution of the multidrug transporter P‐glycoprotein (P‐gp or MDR1) in determining 10‐OHCBZ brain levels by measuring whether this active metabolite is a substrate of P‐gp and the relation between the level of expression of MDR1 and the drug concentration in the same brain tissue specimens. Methods: Steady‐state plasma and brain concentrations (Css) of 10‐OHCBZ were determined intraoperatively in 11 patients by high‐performance liquid chromatography (HPLC) with UV detection. The level of expression of MDR1 mRNA was measured in surgically resected brain tissue by reverse transcriptase polymerase chain reaction (RT‐PCR). The ability of 10‐OHCBZ to act as substate of P‐gp was evaluated by measuring its uptake in cell lines expressing different levels of P‐gp, in the presence or absence of a selective P‐gp inhibitor. Results: OXC was converted to 10‐OHCBZ and to Di‐OHCBZ, the two main metabolites measured in plasma. The brain concentrations of the active metabolite 10‐OHCBZ did not reflect plasma Css. A significant inverse linear correlation was found between 10‐OHCBZ brain‐to‐plasma concentration ratio and the level of brain expression of MDR1 mRNA. In vitro uptake studies demonstrated lower intracellular 10‐OHCBZ levels in cells with higher P‐gp expression. Intracellular drug concentration was increased by XR9576, a specific P‐gp blocker. Conclusions: Pharmacologic failure of OXC in pharmacoresistant epilepsy is unlikely to be due to alterations in drug metabolism. 10‐OHCBZ does not appear to cross the blood–brain barrier by simple diffusion, and it acts as a substrate of P‐gp. The level of expression of MDR1 is inversely correlated with 10‐OHCBZ concentration in the epileptic tissue. P‐gp may play a role in the pharmacoresistance to OXC by determining the attainment of insufficient concentrations of its active metabolite at neuronal targets.
Prolonged Exposure to Lead Lowers the Threshold of Pentylenetetrazole‐induced Seizures in Rats
Authors: Arrieta Oscar , Palencia Guadalupe , García‐Arenas Guadalupe , Morales‐Espinosa Daniela , Hernández‐Pedro Norma , Sotelo Julio 
Published: September 2005

Summary:  Purpose: The aim of this work was to study the effects of prolonged exposure to lead on the threshold of experimental seizures induced by pentylenetetrazole (PTZ). Methods: The 120 Wistar male rats were allocated randomly into four groups; (A) controls, and lead‐treatment groups (B, C, and D) that received lead acetate in the drinking water for a period of 30 days at concentrations of 250, 500, and 1,000 ppm, respectively. After exposure, a trial of PTZ‐induced seizures was conducted in all groups, and blood contents of lead were determined by atomic absorption spectrophotometry. Results: Blood lead contents increased in a dose‐dependent manner. Time elapsed to develop the first myoclonic jerk and the tonic–clonic seizure was less in all lead‐exposed groups than in controls. This effect was greater in the groups administered 500 and 1,000 ppm of lead. The required doses of PTZ to induce myoclonic jerks and tonic–clonic seizures were lower in lead‐exposed rats than in controls. Conclusions: We found a reduction in the threshold for seizures in rats whose blood contents of lead were similar to those of humans from some areas of urban centers with high levels of air pollution.