Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1987, a 69-year-old female suffering from epilepsy and right hemiparesis was admitted to the hospital and given conservative therapy. During the next three weeks she became a stuporous state. Steroids were then prescribed, and she made a complete recovery. Following hormonal and immunological investigations, a diagnosis of Hashimoto's disease with hypothyroidism was made. Following her discharge, thyroxin and anticonvulsant treatments continued. On May 30, 1989, at the age of seventy-one, the patient was found lying unconscious at home, and taken to our hospital. She had signs of a confused state, and seizures of her right arm on admission. Cranial computed tomography (CT) revealed a low density area in the left parieto-occipital lobe, which was heterogeneously enhanced by contrast medium. Magnetic resonance imaging (MRI) showed a lesion of low signal intensity in T1-weighted images and high signal intensity in T2-weighted images, which was homogeneously enhanced by Gd DTPA. Cerebral angiography disclosed no abnormality. Two weeks later, follow-up CT showed that the lesion had become larger and markedly enhanced. A brain tumor, probably malignant lymphoma, was suspected. On June 14, stereotaxic biopsy of the enhanced lesion was performed. Histopathological examination disclosed dense infiltration of the entire walls of many small parenchymal vessels, both arterioles and venules, by lymphocytes. Treatment for angiitis (betamethasone 16 mg daily) was started on June 20, then gradually tapered, and the lesion diminished on CT. Our case has some features of both isolated angiitis of the central nervous system and encephalopathy in compensated Hashimoto's disease. It is suggested that some common base of the autoimmune diseases exists in this case.
 ...
PMID:[Isolated angiitis of the CNS associated with Hashimoto's disease]. 161 79

The ability of steroids to influence brain excitability is well documented. Certain 3 alpha-hydroxylated pregnanes are known to possess anticonvulsant and sedative-hypnotic/anesthetic properties. It has been observed that the seizure susceptibility in menstruating women with catamenial epilepsy appears to be correlated with changes in ovarian steroid levels. However, the underlying mechanism of these steroid influences on brain activity has only been recently revealed by pharmacological studies. These studies have provided compelling evidence for the presence of a novel steroid recognition site on the GABAA-benzodiazepine receptor complex (GBRC). Steroids may interact with this site with high affinity and stereospecificity to enhance chloride channel conductance in a manner similar to that produced by benzodiazepines (BZs) or barbiturates. The existence of such a steroid site on the GBRC is further supported by recent experiments involving the transfection of GABAA receptor cDNAs into a human embryonic kidney cell line. Based on the knowledge of the structure-activity requirements for the interaction of steroids with this novel recognition site, it is conceivable that the development of new anticonvulsant steroids with high therapeutic indices can be achieved.
 ...
PMID:Anticonvulsant steroids and the GABA/benzodiazepine receptor-chloride ionophore complex. 217 79

Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme-containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate peroxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving gamma-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment.
 ...
PMID:Post-traumatic epilepsy: cellular mechanisms and implications for treatment. 222 73

A study of 170 patients with juvenile rheumatoid arthritis and a review of the literature indicate that this disease can significantly affect the central nervous system. Signs of CNS dysfunction were observed in 13 children. During the acute toxic stages the EEG is abnormal in many cases. Other manifestations of toxic encephalopathy such as irritability, drowsiness, stupor, convulsions and marked meningismus may be evident in severe cases. Meningitis is often suspected but ruled out by the finding of normal CSF. Steroids can rapidly improve the condition of these children. If ;unexplained' seizures occur during the chronic stage, the diagnosis of cerebral vasculitis should be entertained.
 ...
PMID:Cerebral complications in juvenile rheumatoid arthritis. 466 94

A 32-year-old woman was bedridden for a year because of chronic pain and headaches. She had insomnia, depression, suicidal thoughts and a severe chemical allergy. She had been on steroid therapy for two years and became Cushingoid with striae in the arm pits, groins and abdomen. However, she had no hypertension, nor the buffalo fat and hirsutism. She was very edematous, with a weight gain from 112 to 180 lbs. The fluid retention did not conform to the syndrome of inappropriate antidiuretic hormone. Studies revealed abnormal scalp EEG discharges and high-voltage seizure discharges in the posterior thalamus. Electrothalamic stimulation suppressed the thalamic discharges and relieved the patient's pelvic pain and headaches. After one month of several thalamic stimulations per day, she was able to get out of bed and ambulate. In addition, the patient no longer was edematous and was tolerating perfumes and floor detergents. Steroids were progressively reduced without complications of withdrawal. She went from a completely steroid dependent state to independent during the first 1-1/2 yrs of thalamic stimulation. With continued thalamic stimulation she has done well for 8-1/2 yrs, weighs 112 lbs, keeps house and drives a car. It's speculated the illness is a chronic pain multiple syndrome predominantly due to mesothalamic discharges and body infirmities. The mesothalamic discharge implicated neural networks, which represent biologic systems, i.e. pain, sleep, fluid retention, etc. Therapeutic stimulation attenuates the discharges and the neural networks return to their normal set points of homeostasis.
 ...
PMID:Mesothalamic discharge in a chronic pain, allergy and fluid retention syndrome (case report). 766 2

From 1986 to February 1993, 40 children aged 2 months to 18 years (average age 10.4 +/- 5.8 years) underwent heart transplantation. Indications for transplantation were idiopathic cardiomyopathy (52%), congenital heart disease (35%) with and without prior repair (71% and 29%, respectively), hypertrophic cardiomyopathy (5%), valvular heart disease (3%), and doxorubicin cardiomyopathy (5%). Patients were managed with cyclosporine and azathioprine. No prophylaxis with antilymphocyte globulin was used. Steroids were given to 39% of patients for refractory rejection, but weaning was always attempted and generally successful (64%). Five patients (14%) received maintenance steroids. Four patients died in the perioperative period and one died 4 months later. There have been no deaths related to rejection or infection. Average follow-up was 36 +/- 19 months (range 1 to 65 months). Cumulative survival is 88% at 5 years. In patients less than 7 years of age, rejection was monitored noninvasively. In the first postoperative month, 89% of patients were treated for rejection. Freedom from serious infections was 83% at 1 month and 65% at 1 year. Cytomegalovirus infections were treated successfully with ganciclovir in 11 patients. No impairment of growth was observed in children who underwent transplantation compared with a control population. Twenty-one patients (60%) have undergone annual catheterizations and no sign of graft atherosclerosis has been observed. Seizures occurred in five patients (14%) and hypertension was treated in 10 patients (28%). No patient was disabled and no lymphoproliferative disorder was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pediatric heart transplantation without chronic maintenance steroids. 831 43

Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans.
 ...
PMID:Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice. 912 7

Neurocysticercosis, the most common parasitic disease of the central nervous system, was treated surgically for a long time. Praziquantel (an isoquinolone) and albendazole (an imidazole) are anticysticercal drugs that are currently being used for the treatment of neurocysticercosis. Both have been reported to eliminate or markedly reduce the number and size of cysticerci. Albendazole is less expensive than praziquantel, and is as effective when given for 8 days as compared to longer periods. In a small number of comparative trials, albendazole appeared to be slightly more effective than praziquantel for the treatment of parenchymal cysticercosis. Albendazole has also been found effective in ventricular, subarachnoidal and racemose forms of the disease. However, the response to treatment is not universal. Treatment with these drugs has been associated with a high frequency of adverse reactions, probably due to the host's inflammatory reaction to the dying parasites. Headache, nausea and seizures are common but usually transient. Steroids appear to ameliorate these effects and their concomitant administration has been advocated. However, no data are available to support this view. The rationale of medical therapy in spinal cysticercosis is presently based on the reported efficacy of anticysticercal drugs in cerebral cysticercosis. A marked improvement in an associated seizure disorder following anticysticercal therapy has been observed. Though seizure control is better, the total duration of anti-epileptic drug therapy has not been determined. Some single enhancing computed tomography lesions in patients of epilepsy may be benign forms of neurocysticercosis. The spontaneous resolution of a majority of these lesions has led to doubts of them being merely infective in aetiology. Also, a controlled trial could not demonstrate any beneficial effect of albendazole on such lesions. Hence, most authors recommend that these patients should be treated with anti-epileptic drugs only. Doubts persist about the efficacy of anticysticercal drugs in altering the natural course of the disease and the reported tendency of cysticercus lesions to resolve.
 ...
PMID:Drug treatment of neurocysticercosis. 932 40

A novel computational technology derived from gene structure has been developed for screening, selecting, and designing pharmaceutical candidates. Pharmacophores, or three-dimensional molecular blueprints, were created by docking known active structures into specific sites in partially unwound DNA. The pharmacophores are composites of the van der Waals surfaces and hydrogen bonding functional groups of active molecules. Once created, molecules can be inserted into the pharmacophores and degree of fit quantitated by the volume of the molecule that fits within the composite surface and the magnitude of electrostatic interactions with charged atoms on the pharmacophore. Here, we describe endocrine pharmacophores and in particular the estrogen pharmacophore derived by docking active ligands into partially unwound DNA. Fit of candidate structures into the estrogen pharmacophore correlated with estrogenic (uterotropic) activity. For example, the super active estrogens moxestrol and 11beta-acetoxyestradiol fit better within the site than estradiol. Bisphenol A, a putative endocrine disrupter with suspected estrogenic activity, was a poor fit in the pharmacophore. Consistent with this prediction, bisphenol A was recently shown to lack uterotropic activity. The capacity of the endocrine pharmacophores to predict certain nontarget activities was demonstrated by using the antiandrogen cyproterone acetate that did not fit the estrogen or thyroid pharmacophores but fit partially into the progestin and glucocorticoid pharmacophores. Cyproterone acetate has been reported to have weak progestational and glucocorticoid activities. The pharmacophores provide for the first time a multidimensional computational method that can simultaneously predict multiple activities of diverse molecular structures.
Steroids 1999 Sep
PMID:Multidimensional screening and design of pharmaceuticals by using endocrine pharmacophores. 1050 11

Benign rolandic epilepsy is the most common epilepsy of childhood. Regarding seizure control typical and atypical rolandic epilepsies have a reasonable prognosis. In a recent prospective study STM was shown to control seizures in BECTS and STM is regarded as first line drug for this epilepsy in countries having access to this drug. Otherwise, CBZ is used most often and very effectively in BECTS. However, CBZ has the disadvantage to worsen clinical and EEG features up to the precipitation of CSWS in few patients. Epileptic seizures are often not the main problem in atypical rolandic epilepsies like CSWS or LKS and the amelioration of cognitive dysfunction by epileptic discharge is the prominent aim of an AED therapy. Steroids seem the have the best efficacy in these cases.
 ...
PMID:Treatment in typical and atypical rolandic epilepsy. 1123 Dec 30


1 2 3 4 Next >>