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)

Recurrent heritable childhood myoglobinuria is a potentially fatal entity (mortality up to 35%) in which prompt diagnosis and treatment are critical. Sixty childhood cases have been reported between 1910 to 1988, most with undiagnosed etiologies. We have studied an additional 40 cases referred to CPMC (1980-1988), suggesting that this condition is largely underdiagnosed or unreported. We have found important differences between the childhood and adult-onset cases. Of 77 cases of adult-onset recurrent myoglobinuria, 45% have been diagnosed biochemically. In contrast, only 30% of the 60 childhood cases from the literature have been diagnosed; 11 with CPT deficiency and 7 with various glycolytic defects, and only 5 of our 40 childhood cases have been diagnosed, all with CPT deficiency. The 100 combined childhood cases can be divided into an exertional group (type I) with exertion as the leading precipitating factor (46 literature and 10 CPMC cases), a toxic group (type II) with infection and/or fever as the primary precipitant (14 literature and 23 CPMC cases), and 7 undefined cases. The type I group resembles the adult-onset group in which exercise is also the leading precipitating factor. There is a slight female predominance (male/female = 1:1.3) in the toxic group vs. a marked male predominance in the exertional and adult groups (4:1). Only 4 of 37 cases (11%) of the toxic group are diagnosed (all with CPT deficiency) vs. 19 of 56 cases (34%) of the exertional group (12 CPT, 7 glycolytic) and 45% of the adult group. The toxic group is also differentiated by a higher mortality rate and by the presence of additional clinical features, including ictal bulbar signs (8 of 18), encephalopathy (4 of 19), and seizures (2 of 7), as well as persistent cardiac abnormalities, developmental delay (4 of 17), and dysmorphic features (2 of 9). These clinical characteristics clearly differentiate the childhood from the adult cases and suggest the presence of more generalized disease processes and different biochemical etiologies. A study of the heritable causes of myoglobinuria is important because identification of the biochemical defect may elucidate the pathogenetic mechanism of the myoglobinuria and facilitate the development of rational treatment strategies aimed at circumventing or correcting the metabolic block.
 ...
PMID:Recurrent childhood myoglobinuria. 226 36

Defective activity of carnitine palmitoyltransferase I was demonstrated in fibroblasts derived from a patient with hypoketotic hypoglycemia. The level of activity observed was approximately 10% of the control mean. Oxidation of palmitate by intact fibroblasts was reduced to 5% of control values. The patient presented at age 14 months with seizures and was found to have marked hypoglycemia and no ketones in the urine. In response to fasting, she developed hypoglycemia, but the curves for acetoacetate and 3-hydroxybutyrate were flat. Administration of medium-chain triglycerides relieved the hypoglycemia and generated a brisk ketogenesis.
 ...
PMID:Deficiency of carnitine palmitoyltransferase I. 276 84

Human carnitine palmitoyltransferase (CPT) deficiency results in 2 clinical forms: a more common "muscular form" with myoglobinuria with or without delayed or impaired ketogenesis and a rare "hepatic form" with hypoketotic hypoglycemia, encephalopathy and seizures without muscular manifestations. We present 2 patients, a male (patient 1) and a female (patient 2) with infantile "hepatic" CPT deficiency and previously documented CPT1 deficiency in fibroblasts. In patient 2, a deficiency of "total" CPT activity in liver had also been previously documented. We set up an isotope exchange assay system that effectively differentiated CPT1 and CPT2 activities in muscle. We found normal CPT1 and CPT2 activities in our patients under near saturating substrate conditions. The CPT1 and CPT2 activities were suppressed to a strikingly similar degree under different kinetic conditions as compared to control muscle and were found to have similar Km values for carnitine and PCoA. With Km concentrations of carnitine, the mean residual activities of CPT1 for patients 1 and 2 were 49 and 44%, respectively (control range 40-53%); the mean residual activities of CPT2 were 60 and 46%, respectively (control range 49-59%). With Km concentrations of PCoA, the mean residual activities of CPT1 for patients 1 and 2 were 52 and 58%, respectively (control range of 52-59%); mean residual activities of CPT2 were 54% and 56%, respectively (control range of 51-68%). When the Vmax concentration of PCoA was doubled and bovine serum albumin reduced to 0.1%, the mean residual activities of CPT1 for patients 1 and 2 were 69 and 63%, respectively (control range 60-80%). In "muscular" patients, a marked absolute deficiency of CPT2 activity (less than 12% residual) was found with an apparent increased sensitivity to suppression of enzymatic activity when the Km concentration of carnitine was used. We suggest that CPT1 and CPT2 may be separate proteins. Furthermore, CPT1 itself may exist as tissue-specific isoforms being the same protein in liver and fibroblasts and a different protein in muscle. Either could be encoded for by the same or closely related genes.
 ...
PMID:Normal muscle CPT1 and CPT2 activities in hepatic presentation patients with CPT1 deficiency in fibroblasts. Tissue specific isoforms of CPT1? 280 20

We tested the effects of 8-cyclopentyl-1,3 dimethylxanthine (8-CPT) on electrically induced seizures in rats. 8-CPT prolonged secondary seizures and converted partial seizures into generalized motor seizures, but did not affect primary seizure duration. Because 8-CPT is a potent and specific adenosine antagonist, these results add further support to the hypothesis that endogenous adenosine prevents the spread of epileptic seizures.
 ...
PMID:8-Cyclopentyl 1,3-dimethylxanthine prolongs epileptic seizures in rats. 365 21

A 23-year-old Japanese man presented with status epilepticus unresponsive to medication, respiratory failure, rhabdomyolysis, myoglobinuria, and irreversible renal failure. Muscle biopsy revealed type 1 fiber atrophy and an increased type 2C fibers (7%). His carnitine palmitoyltransferase (CPT) I and II activities were 0.06 and 0.12 nmol/min/mg protein, as compared with a mean value of 0.22 +/- 0.14 and 0.27 +/- 0.07 nmol/min/mg protein, respectively, in control subjects. This appears to be the first report of this disorder presenting as status epilepticus. Metabolic encephalopathy due to CPT deficiency may have presented as status epilepticus. Seizures in the present case may have resulted from the functional disorder of brain due to CPT deficiency.
 ...
PMID:Atypical presentation of carnitine palmitoyltransferase (CPT) deficiency as status epilepticus. 775 48

The effect of a selective adenosine antagonist, 8-cyclopentyl 1,3-dimethylxanthine (8-CPT) was used to examine involvement of adenosine in ictal and postictal events in rats subjected to maximal electroshock (MES). MES induces the ictal event of hindlimb tonic extension (HLTE) followed by postictal depression (PID). 8-CPT 10 mg/kg, ip produced maximal significant reduction of PID without affecting HLTE, further confirming involvement of adenosine in PID. Carbamazepine and sodium valproate were studied independently and were coadministered with 8-CPT to determine if their anticonvulsant activity was modulated by adenosine and if they altered PID. 8-CPT did not antagonize the seizure protection afforded by CBZ or SV. CBZ significantly reduced postictal events whereas SV had no significant effect. These observations further confirm a role for adenosine in postictal phenomena.
 ...
PMID:Involvement of adenosine in postictal events in rats given electroshock. 813 42

Effects of the cyclic AMP agonists 8-(4-chlorophenylthio)-adenosine 3':5' cyclic monophosphate (CPT-cAMP), dibutyryl cyclic AMP (dbcAMP) and forskolin were studied on extracellular field potentials in rat neocortex slices in vitro. CPT-cAMP and forskolin produced a prolonged enhancement of epileptiform activity resulting from removal of Mg2+ from the bathing medium. DbcAMP had no apparent effect except at high concentrations (1 mM), when it reduced bursting activity. Field potentials observed following electrical stimulation of the corpus callosum in the presence of Mg2+ were enhanced by CPT-cAMP and dbcAMP; however forskolin was without effect. Intracellular recording techniques demonstrated a transient excitatory influence of dbcAMP. The results indicate a role for cyclic AMP in seizure mechanisms.
 ...
PMID:Cyclic AMP analogues increase excitability and enhance epileptiform activity in rat neocortex in vitro. 839 51

We describe the term male infant of asymptomatic, healthy nonconsanguineous parents presenting on the first day of life with nonketotic hypoglycemia, seizures, hepatomegaly, cardiomegaly with biventricular hypertrophy, and ventricular arrhythmias. Cranial ultrasound revealed cystic dysplasia with several foci of hyperechogenicity within the right basal ganglia. Free carnitine was markedly decreased in the urine and plasma with a pronounced elevation of plasma long-chain acylcarnitines. Fibroblast carnitine palmitoyltransferase II activity was reduced to 26% and 38% in the father and mother, respectively. The infant expired on day 5 of life from malignant ventricular tachy-arrhythmias. Diffuse lipid accumulation was evident at autopsy, including in the liver, heart, kidney, adrenal cortex, skeletal muscle, and lungs. This new case of infantile CPT-II deficiency illustrates the severity of the early onset form of CPT-II deficiency.
 ...
PMID:Fatal carnitine palmitoyltransferase II deficiency in a newborn: new phenotypic features. 992 37

The introduction of tandem mass spectrometry to newborn screening has substantially expanded our ability to diagnose metabolic diseases in the newborn period. We report the first case of neonatal carnitine palmitoyltransferase deficiency II detected by expanded newborn screening with tandem mass spectrometry. The neonate presented with dysmorphic facial features, structural malformations, renal failure, seizures, and cardiac arrythmias and died on the third day of life. This experience illustrates the importance of expanded newborn screening to avoid missing a metabolic diagnosis in early infantile death.
 ...
PMID:Detection of neonatal carnitine palmitoyltransferase II deficiency by expanded newborn screening with tandem mass spectrometry. 1138 1

In this study the role of adenosine A1 and A2A receptors of the hippocampal CA1 region on piriform cortex-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of piriform cortex. In fully kindled rats, N6-cyclohexyladenosine (CHA; a selective A1 receptor agonist), 1,3-dimethyl-8-cyclopenthylxanthine (CPT; a selective A1 receptor antagonist), CGS21680 hydrochloride (CGS, a selective A2A receptor agonist) and, ZM241385 (ZM, a selective A2A receptor antagonist) were microinfused bilaterally into the hippocampal CA1 region. Rats were stimulated and seizure parameters were measured. Obtained results showed that microinjection of CHA (10 and 100 microM) decreased the afterdischarge duration (ADD), stage 5 seizure duration (S5D) and seizure duration (SD), and significantly increased the latency to stage 4 (S4L). Intra-hippocampal CPT increased ADD at the dose of 20 microM. Pretreatment of rats with CPT (10 microM) before CHA (10 microM), significantly reduced the effect of CHA on seizure parameters. On the other hand, microinjection of CGS (200 and 500 microM) increased ADD, but of ZM had no effect on seizure parameters. Pretreatment of rats with ZM (50 microM) before CGS (500 microM), significantly reduced the effect of CGS on seizure parameters. The results suggest that the facilitatory role of the hippocampal CA1 region in relaying or spreading of piriform cortex kindled seizures is decreased by the activation of adenosine A1 receptors and increased by A2A receptors.
Seizure 2006 Jan
PMID:Adenosine A1 and A2A receptors of hippocampal CA1 region have opposite effects on piriform cortex kindled seizures in rats. 1633 18


1 2 3 Next >>