Contribution of ambulatory EEG recording (Medilog 9000) in a population of epileptics

Thirty-four epileptic patients, aged 9 to 36, were submitted to A/EEG between May 1987 and July 1988. All patients had a thorough clinical and EEG work-up including long-term conventional EEG, afternoon polygraphic sleep recording and, in some cases, full-night EEG and video monitoring. Patients were divided into 2 groups: group I included 19 patients (18 with symptomatic partial epilepsy (SPE) and 1 with idiopathic generalized epilepsy (IGE) in whom no seizure had ever been recorded in spite of EEG recordings averaging a total of 16 hrs 10 min, awake and asleep); group II included 15 subjects (6 with SPE, 5 with IGE, 3 with symptomatic GE and 1 with undetermined epilepsy) in whom one or several seizures had been recorded. A/EEG was performed in order to: 1) obtain better clinical and EEG characterization of seizures, 2) study the circadian distribution of seizures, 3) verify the efficacy of drug treatment and, 4) establish the epileptic or non-epileptic nature of some ictal events. The results of A/EEG were considered positive in 52.63% of group I patients and in 93.33% of group II patients. The authors discuss the specific advantages of A/EEG vs conventional EEG: recording of seizures with random occurrence, of seizures accompanied by falls, checking the remission of seizures.     

Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam.) Kosterm. (Lauraceae) calices from Amazonian Ecuador.

Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human plasma, at investigating the mechanism underlying such activity and at evaluating the potential antithrombotic activity of subacute treatment of mice with Ocotea essential oil. In vitro Ocotea essential oil and trans-cinnamaldehyde inhibited arachidonic acid-, U46619-, ADP-, phorbol12-myristate13-alcetate-, collagen-induced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma; Ocotea oil and trans-cinnamaldehyde competitively antagonized contractions induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring (K(B) = 18 and 3.2 microg ml(-1), respectively). In vivo Ocotea oil, orally administered in a subacute treatment (30-100 mg kg(-1) day(-1) for 5 days) to mice, prevented acute thrombosis induced by collagen-epinephrine intravenous injection. This antithrombotic activity was not accompanied by pro-haemorragic side effect, as detected by the inactivity in bleeding test, thus showing a favourable safety profile compared to the conventional antiplatelet agent, acetylsalicylic acid. Present findings indicate that Ocotea essential oil possesses potent and safe antithrombotic activity attributable to its antiplatelet and vasorelaxant effects. The main constituent trans-cinnamaldehyde seems to be the primary responsible for this activity through a putative mechanism involving the inhibition of thromboxane A2 receptors.     

BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

X-ray computed tomography of thoracic injuries. Apropos of 40 cases]

On chest radiographs, the precise assessment of thoracic injuries consecutive to blunt trauma is often compromised by the nonspecific appearance of many lesions. Furthermore, significant injuries are frequently overlooked. However, the management of the patients with chest trauma is still often based primarily upon clinical and radiographic findings and Computed Tomography (CT) is often performed secondarily on the basis of unexplained clinical signs or suspected radiographic abnormality. Some authors have reported that CT was a highly sensitive method for detecting thoracic lesions frequently not seen or underestimated on conventional supine chest radiographs. However, the value that these new CT findings could have in the therapeutic management of these patients, have not been systematically investigated to our knowledge, except in a limited series suggesting that the course of critically ill patients could be substantially altered after thoracic CT. In order to estimate the role of early CT in the management of patient care, we report the therapeutic consequences of CT findings in forty patients who we report the therapeutic consequences of CT findings in forty patients who had a thoracic CT within few hours following a chest injury. We showed that early thoracic CT scan in patients with blunt trauma detected significantly more lesions than did chest X-Ray and appreciably modified the treatment modalities in 70% of our patients. We then recommend that all the patients admitted in ICU after chest trauma undergo a thoracic CT scan as soon as possible in order to optimize their treatment modalities.     

Opioid deltorphin C analogues containing cis- or trans-2- or 3- or 4-aminocyclohexanecarboxylic acid residues

The solid phase synthesis, based on the Fmoc chemical protocol, was used to prepare ten deltorphin C (Del-C; H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues containing cis- and trans- 2 or 3- or 4- aminocyclohexanecarboxylic acid (ACCA) residues at position 2. ACCA-peptides showed high resistance to degradation by plasma or brain enzymes, negligible affinity for the kappa-binding site and modest delta- and/or mu-receptor affinities. Both [cis-3-ACCA2]Del-C analogues and one trans isomer are the only deltorphin analogues of this series exhibiting an appreciable delta-affinity and selectivity. These data suggest that the presence of a conformationally constrained ACCA residue in position 2 of the "message" sequence of deltorphin C is slightly tolerated.     

Benzodiazepine receptor ligands. III. Synthesis and biological evaluation of 2- and/or 3-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides

A new series of 2- and/or 3-substituted pyrazolo [5,1-c][benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their benzodiazepine receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed.     

Further studies on the Dmt-Tic pharmacophore: hydrophobic substituents at the C-terminus endow delta antagonists to manifest mu agonism or mu antagonism

Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K(i) values with either [(3)H]DPDPE (delta(1) agonist) or [(3)H]N, N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH(2), -NHCH(3), -NH-1-adamantyl, -NH-tBu, -NH-5-tetrazolyl) had high delta affinities (K(i) = 0.16 to 1 nM) with variable mu affinities to yield nonselective or weakly mu-selective analogues. N, N-(Me)(2)Dmt-Tic-NH-1-adamantane exhibited dual delta and mu receptor affinities (K(i)delta = 0.16 nM and K(i)mu = 1.12 nM) and potent delta antagonism (pA(2) = 9.06) with mu agonism (IC(50) = 16 nM). H-Dmt-betaHTic-OH (methylene bridge between C(alpha) of Tic and carboxylate function) yielded a biostable peptide with high delta affinity (K(i) = 0.85 nM) and delta antagonism (pA(2) = 8.85) without mu bioactivity. Dmt-Tic-Ala-X (X = -NHCH(3), -OCH(3), -NH-1-adamantyl, -NHtBu) exhibited high delta affinities (K(i) = 0.06 to 0.2 nM) and elevated mu affinities (K(i) = 2.5 to 11 nM), but only H-Dmt-Tic-Ala-NH-1-adamantane and H-Dmt-Tic-Ala-NHtBu yielded delta receptor antagonism (pA(2) = 9.29 and 9.16, respectively). Thus, Dmt-Tic with hydrophobic C-terminal substituents enhanced mu affinity to provide delta antagonists with dual receptor affinities and bifunctional activity.     

Bilateral frontal polymicrogyria: a newly recognized brain malformation syndrome

BACKGROUND AND OBJECTIVE: Polymicrogyria is a brain malformation characterized by abnormal cortical lamination, excessive cortical folding, and fusion of the cortical molecular layer. Two distinct bilateral localized forms have been described: bilateral perisylvian polymicrogyria, which has proved to be genetically heterogeneous, and bilateral parasagittal parieto-occipital polymicrogyria, which has been described only in sporadic patients. We describe 13 patients with symmetric polymicrogyria of both frontal lobes back to the precentral sulcus: bilateral frontal polymicrogyria (BFP). METHODS: Review of clinical records, brain MRI, and EEG results of 13 patients; correlation with other regional polymicrogyrias. RESULTS: The abnormal cortex extended from the frontal poles anteriorly to the precentral gyrus posteriorly and to the frontal operculum inferiorly and was relatively symmetric in all 13 patients. All patients presented with developmental delay and mild spastic quadriparesis, but variably impaired language development (12/13), mental retardation (11/13), and epilepsy (5/13) also occurred. BFP was sporadic in 13 of 13 patients, but 2 of 13 had consanguineous parents. CONCLUSIONS: BFP extends the spectrum of the recognized bilateral symmetric regional polymicrogyria syndromes.     

Nociceptin/orphanin FQ inhibits ischaemia-induced glutamate efflux from rat cerebrocortical slices

Nociceptin/orphanin FQ (NC), the endogenous ligand for the G-protein coupled nociceptin receptor (NCR), has a modulatory role in various physiological processes including neurotransmitter release. We have examined the effects of NC, the analogues NC(1-13)NH2 and [F/G]NC(1-13)NH2 and the competitive antagonist [Nphe1]NC(1-13)NH2 (Nphe1) on glutamate efflux during an acute simulated ischaemic challenge in rat cerebrocortical slices. The increase in glutamate efflux seen with ischaemia was inhibited by NC (EC50 250 nM). At micromolar concentrations, the analogues were found to have a similar effect on glutamate efflux compared to NC. In all cases, inhibition of glutamate efflux was abolished by Nphe1 (30 microM). These results suggest a neuroprotective action for NC.