UMLS:C0036572 - FACTA Search

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Query: UMLS:C0036572 (seizures)
80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osmotic and ionic balance in the central nervous system is especially regulated by solutes and water transport across the blood-brain barrier. The aim of this study was to investigate the effect of systemic hyperosmolarity on the blood-brain barrier permeability in both sexes after experimentally induced seizures. Eight groups of rats were studied: Group I: female control; Group II: male control; Group III: hyperosmotic female; Group IV: hyperosmotic male; Group V: non-hyperosmotic female + seizure; Group VI: non-hyperosmotic male + seizure; Group VII: hyperosmotic female + seizure; Group VIII: hyperosmotic male + seizure. In female rats with pentylenetetrazol-induced seizures, the extravasation of Evans-blue was greater in the brains of hyperosmotic animals than that in normal rats (P < 0.02). However, in male rats, the extravasation of Evans-blue was similar in the brains of hyperosmotic male rats and normal rats after seizure. Our results concluded that hyperosmotic female rats were shown to have a large increase in blood-brain barrier permeability in comparison to hyperosmotic male rats after pentylenetetrazol-induced seizures.
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PMID:Sex-dependent changes in blood-brain barrier permeability in epileptic rats following acute hyperosmotic exposure. 1139 39

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

The delta(2)- 1,2,3- triazoline anticonvulsants (TRs) may be considered as representing a unique class of "built-in" heterocyclic prodrugs where the active "structure element" is an integral part of the ring system and can be identified only by a knowledge of their chemical reactivity and metabolism. Investigations on the metabolism and pharmacology of a lead triazoline, ADD17014 suggest that the triazolines function as "prodrugs" and exert their anticonvulsant activity by impairing excitatory amino acid (EAA) L-Glutamate (L-Glu) neurotransmission via a unique "dual-action" mechanism. While an active primary beta-amino alcohol metabolite from the parent prodrug acts as an N-methyl-D-aspartate (NMDA)/MK -801 receptor antagonist, the parent triazoline impairs the presynaptic release of L-Glu. Various pieces of theoretical reasoning and experimental evidence have led to the clucidation of the dual-action mechanism. Based on the unique chemistry of the triazolines, and their metabolic pathways, biotransformation products of TRs were predicted to be the beta-amino alcohols V and VA, the alpha-amino acid VI, the triazole VII, the aziridine VIII and the ketimine IX. In vivo and in vitro pharmacological studies of the TR and potential metabolites, along with a full quantitative urinary metabolic profiling of TR indicated the primary beta-amino alcohol V as the active species. It was the only compound that inhibited the specific binding of [3H]MK-801 to the MK-801 site, 56% at 10 micro M drug concentration, but itself had no anticonvulsant activity, suggesting TR acted as a prodrug. Three metabolites were identified; V was the most predominant (45.7 +/- 7.6) % of administered drug, with lesser amounts of VA, (17.3 +/- 5.1) % and very minor amounts of aziridine VIII (4.0 +/- 0.02)%. Since only VIII can yield VA, its formation indicated that the biotransformation of TR occurred, at least in part, through aziridine. No amino acid metabolite was detected, which implied that no in vivo oxidation of V or oxidative biotransformation of TR or aziridine by hydroxylation at the methylene group occurred. While triazoline significantly decreased Ca(2+) -dependent, k(+)-evoked L-Glu release (83% at 100 micro M drug concentration ), some triazolines showed an augmentation of 50-63%, in the Cl(-) channel activity, a useful membrane action that reduces the excessive L-Glu release that occurs during epileptic seizures. The high anticonvulsant activity of TRs in a variety of seizure models including their effectiveness in the kindling model of complex partial seizures may be due to their unique dual-action mechanism whereby the TR and V together effectively impair both pre- and postsynaptic aspects of EAA neurotransmission; thus the TRs have clinical potential in the treatment of complex partial epilepsy which is refractory to currently available drugs. Since there is strong evidence that L-Glu plays an important role in human epilepsy as well as in brain ischemia/stroke, and since the TRs act by inhibiting EAA neurotransmission, it was logical to expect that the anticonvulsant TRs may evince beneficial therapeutic potential in cerebral ischemia resulting from stroke as well. And indeed, several TRs, when tested in the standard gerbil model of global ischemia did evince remarkable ability to prevent neuronal death.
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PMID:Rational drug design and the discovery of the delta2-1,2,3-triazolines, a unique class of anticonvulsant and antiischemic agents. 1287 Oct 87

As part of our study, a series of N-phenyl- and N-benzyl-bicyclo [2.2.1] hept-5-ene-2,3-dicarboximides [III-XVI], structurally related to the previously described N-phenyl- or N-pirydyl-3-arylpyrrolidine-2,5-dione [I, II], were synthesized and tested for their anticonvulsant activity in the maximum electroshock seizure (MES) and metrazole seizure threshold (sc. MET) tests. The most potent in the maximum electroshock seizure (MES) test were compounds with methyl [III] and chloro [XI] substituents at position -2 of the aromatic ring, whereas of all the synthesized compounds, only N-(2-methoxybenzyl)-bicyclo [2.2.1] hept-5-ene-2,3-dicarboximide [XII] was active in the sc. MET. Compounds with substituents at position -3 or -4 of the aromatic ring were found to be less active [V, VI, XIII and XIV], or devoid of activity [VII, IX, XV and XVI]. In contrast, the N-(4-chlorophenyl)-bicyclo [2.2.1] hept-5-ene-2,3-dicarboximide [VIII] at a dose of 100 mg/kg was active in the MES test.
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PMID:Synthesis and anticonvulsant activity of a series of N-substituted bicyclo [2.2.1] hept-5-ene-2,3-dicarboximides. 1619 14

Carbonic anhydrases (CAs) are important enzymes in the central nervous system (CNS), where they participate in regulating cerebrospinal fluid (CSF) secretion, blood-brain barrier and glial cell function. Using RT-PCR we found CA XII mRNA in rat and mouse brain. Cloning of rat CA XII revealed 94% homology with the mouse CA XII. To map the putative functional roles of different CAs, we studied the expression and localization of CA II, CA IV, CA VII, CA-related protein (CA-RP) VIII and CA XII mRNAs in rat brain after kainic acid induced epileptic seizures using Northern blot analysis and in situ hybridization. The expression of CA IV, CA VII and CA-RP VIII was somewhat similar: they were expressed in the cortex, hippocampus and midbrain structures and their expression did not change after the kainic acid treatment. The expression of CA II was concentrated in the white matter structures, which is in line with the preferential expression of CA II in the oligodendrocytes. High levels of CA II mRNA were also detected in the choroid plexus. Surprisingly, CA II was induced 3-12 h after seizures in the vulnerable CA1 region. CA XII was expressed in dentate granule cells, cortex and choroid plexus. Kainic acid stimulated CA XII expression throughout the cortical layer I. The observed hippocampal induction of CA II may indicate a pro-apoptotic and/or epileptogenic role of CA II after prolonged seizures. The physiological significance of the observed cortical induction of CA XII remains obscure. Cytosolic CA II is known to participate in CSF secretion, and the high expression of CA XII in the choroid plexus suggests an analogous role for this membrane-bound isozyme.
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PMID:Expression of carbonic anhydrases II, IV, VII, VIII and XII in rat brain after kainic acid induced status epilepticus. 1627 2

A series of aroxyacetamides and aroxyethylamines were prepared and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). Most of them exhibited anticonvulsant activity in the MES screen (mice, i.p.) in the doses up to 300 mg/kg b.w. The most active compound was XVI, which given in the dose 100 mg/kg b.w. produced 100% anticonvulsant protection after 0.5 h without neurotoxicity. The most promising compound in the VIa phase (rats, p.o.) was VIII, which produced higher anticonvulsant protection (to 75% at 0.5 h).
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PMID:Preliminary evaluation of anticonvulsant activity of some aroxyacetamides and aroxyethylamines. 1645 83

To continue our systematic SAR studies a series of N-phenylamino derivatives of 2-azaspiro[4.4]nonane-, 2-azaspiro[4.5]decane-, 6-methyl-2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine-2,5-dione were synthesized and tested for their anticonvulsant activity in the maximum electroshock seizure (MES) and subcutaneous metrazole seizure threshold (sc. Met) tests. Among those molecules the most potent were N-(4-methylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [V], N-(2-trifluoromethylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [VI], N-(3-methylphenyl)-amino-2-azaspiro[4.5]decane-1,3-dione [VIII] and N-(4-methylphenyl)-amino-6-methyl-2-azaspiro[4.5]decane-1,3-dione [XIV], which inhibited the seizures mainly in the sc. Met test. The obtained results revealed that anticonvulsant activity depended on the presence and the position of the methyl or trifluoromethyl groups at the aryl moiety, as well as the size and the manner of attachment of the cycloalkyl system at the position-3 of the pyrrolidine-2,5-dione ring.
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PMID:Synthesis and anticonvulsant properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane, 2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine-2,5-dione. Part IV. 1751 72

The synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- succinimides [I-XXII] differently substituted at the position-3 of imide ring have been described. The profile of pharmacological activity of these compounds was examined by a maximal electroshock (MES) and pentylenetetrazole (scPTZ) tests, whereas their neurotoxicity was determined using a rotarod screen. The results obtained revealed that the anticonvulsant activity depended mainly on the kind of substituents at the position-3 of pyrrolidine-2,5-dione ring. The most active were 3,3-dialkyl-pyrrolidine-2,5-diones [IX-XVIII] as well as compounds with 3-methylcyclohexane moiety as a spiro nucleus at position-3 of the imide ring [I-IV]. The 3-cyclohexylsuccinimides [V-VIII] with cyclohexane ring as a flexible fragment were less active, whereas unsubstituated derivatives [XIX-XXII] were devoid of activity in both tests applied. In addition, the anti-seizure protection depended on the position of methyl group at the pyridine moiety. The most potent were compounds with the methyl substituent at the position-4 [II, VI, XVII] or -6 [XI, XIV]. It should be noted, that in the whole series the most active was 1-(4-methyl-2-pyridinyl)-3-cyclohexyl-pyrrolidne-2,5-dione [VI], which showed the anti-scPTZ protection at the dose of 30 mg/kg.
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PMID:Synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- 3-substituted pyrrolidine-2,5-dione derivatives. 1905 87

Cholesterol granulomas are characterized by an inflammatory reaction with giant cells in response to products of hemoglobin degradation. It can develop in different tissues throughout the body, but as a lesion of the petrous apex it is an own entity. Clinical symptoms may be hearing loss, vertigo, and headache as well as affections of the V-VIII (th) cranial nerves or seizure. Cholesterol granulomas can be identified by typical radiological findings in CT and MRI. Although an unusual entity, cholesterol granulomas are high on the differential of petrous apex lesions and need to be resected via an infralabyrinthine, translabyrinthine or transsphenoidal approach with an establishment of a permanent drainage route in cases of symptomatic clinical presentations.
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PMID:[Petrous apex cholesterol granulomas]. 1991 23

The series of N-[(4-arylpiperazin-1-yl)-alkyl]-3-phenyl- and 3-(3-methylphenyl)-pyrrolidine-2,5-diones [VIII-XXV] were synthesized and evaluated for anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed in mice, using intraperitoneal (ip) maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole-induced (scPTZ) seizure threshold tests. The neurotoxicity was determined applying the rotorod screen. Compounds VIII-XXV revealed protection only in the electrically induced seizures or were inactive. The most active were Mannich bases of 3-(3-methylphenyl)-pyrrolidine-2,5-dione with electron-withdrawing substituents at position-3 of 4-arylpiperazine fragment [XVII, XVIII], as well as compounds with ethylene or propylene spacer between imide and 4-arylpiperazine nitrogen atoms [XX-XXII, XXV]. All these compounds showed anti-MES protection in mice at doses of 100 mg/kg. Additionally, when given orally, compound XVIII was also active in rats MES screen at a dose of 30 mg/kg.
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PMID:Synthesis, physicochemical and anticonvulsant properties of new N-[(4-arylpiperazin-1-yl)alkyl]-3-phenyl- and 3-(3-methyl-phenyl)-pyrrolidine-2,5-diones. 2005 May 28

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