ABSTRACT
OBJECTIVE: To test serum S100B protein levels in patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) and controls. METHODS: 87 patients with SLE, 23 with and 64 without neuropsychiatric involvement, and 25 control subjects were prospectively evaluated. NPSLE diagnosis was made according to the American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Serum S100B protein levels were determined with a luminescence immunoassay. Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests. RESULTS: Among the patients with NPSLE, 9 presented psychosis; 4, cranial neuropathy; 3, cerebrovascular disease; 1, seizures; 1, chorea; 1, peripheral polyneuropathy; 1, multiplex mononeuropathy; 3, dementia. Serum concentrations of S100B protein were significantly higher in patients with NPSLE (median 0.164 ng/ml, interquartile range 0.113-0.332) than in non-NPSLE patients (0.062 ng/ml, 0.026-0.109) and controls (0.088 ng/ml, 0.013-0.124) (p<0.001). Patients with anti-dsDNA antibodies had higher S100B protein levels (p = 0.001). No significant associations were found of lupus activity (among non-NPSLE cases), antiphospholipid antibodies, and reduced complement levels with S100B concentration. CONCLUSIONS: Serum S100B protein level is raised in NPSLE, reflecting continuing neurological damage. The association of anti-dsDNA antibodies with higher S100B protein concentration deserves further study.
Subject(s)
Lupus Erythematosus, Systemic/blood , Lupus Vasculitis, Central Nervous System/blood , Nerve Growth Factors/blood , S100 Proteins/blood , Adult , Antibodies, Anticardiolipin/blood , Antibodies, Antinuclear/blood , Biomarkers/blood , Case-Control Studies , Female , Humans , Lupus Coagulation Inhibitor/blood , Lupus Vasculitis, Central Nervous System/diagnosis , Male , Middle Aged , Prospective Studies , ROC Curve , S100 Calcium Binding Protein beta Subunit , Sensitivity and SpecificityABSTRACT
N-Methyl-D-aspartate (NMDA) receptor antagonists cause hyperlocomotion and cognitive deficits in rodents, and caffeine-tolerant mice show diminished locomotor response to NMDA receptor antagonists. The aim of this study was to evaluate the effect of subchronic caffeine treatment on MK-801-induced hyperlocomotion, ataxia and cognitive deficits, as well as amphetamine-induced hyperlocomotion in mice. Mice were treated subchronically with caffeine (0, 0.1, 0.3 and 1 mg/ml and 1, 3 and 7 days) and evaluated for locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task) and ataxia. Hyperlocomotion induced by MK-801 (0.25 mg/kg i.p.) was diminished after 3 days and almost abolished after 7 days of caffeine treatment at the 1 mg/ml dose, and this effect was also dose-dependent. Ataxia induced by 0.5 mg/kg MK-801 was not affected by caffeine treatment, but a short-lived hyperlocomotor effect was observed. Performance deficit in the inhibitory avoidance task induced by MK-801 (0.01 mg/kg) was prevented in mice treated with caffeine for 7 days at 1 mg/ml, and perseverative errors in the T-maze by MK-801 (0.4 mg/kg) were attenuated. The locomotor effect of amphetamine (5 mg/kg) was unaffected by subchronic caffeine treatment. The findings that hyperlocomotion and cognitive effects induced by MK-801 can be specifically influenced by reduced adenosinergic activity agree with a model of adenosine hypofunction in schizophrenia, since NMDA receptor antagonists are pharmacological models for this disorder.
Subject(s)
Caffeine/pharmacology , Central Nervous System Stimulants/pharmacology , Cognition/drug effects , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Locomotion/drug effects , Adenosine/pharmacology , Amphetamine/pharmacology , Animals , Ataxia , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Interactions , Humans , Male , Mice , Receptors, N-Methyl-D-Aspartate/physiology , Schizophrenia/physiopathologyABSTRACT
OBJECTIVE: To assess whether serum S100B levels could reflect a glial response in patients with epilepsy secondary to neurocysticercosis (NCC) and with idiopathic epilepsy. SUBJECTS AND METHODS: Serum S100B levels were measured using an immunoluminometric assay in 20 patients with focal epilepsy related to chronic NCC (NCC group), and 19 patients with focal epilepsy (EPI group), matched by epidemiological and clinical data. Epileptic patients were compared with 20 healthy controls (CON group) matched by age and sex. RESULTS: No difference was observed in S100B levels among NCC, EPI and CON groups (P>0.39). Serum S100B levels were not affected by antiepileptic drugs, frequency and type of seizures. Preliminarily, significantly higher levels of S100B were observed in patients with bilateral electroencephalographic (EEG) findings than in patients with unilateral and normal EEG findings (P<0.05). CONCLUSION: Serum S100B is normal in patients with focal epilepsy related or not to chronic NCC.
Subject(s)
Epilepsy/blood , Nerve Growth Factors/blood , Neurocysticercosis/blood , S100 Proteins/blood , Acute Disease , Adult , Case-Control Studies , Electroencephalography , Epilepsy/diagnosis , Female , Humans , Male , Neurocysticercosis/diagnosis , S100 Calcium Binding Protein beta SubunitABSTRACT
CONTEXT: Machado-Joseph Disease (MJD/SCA3) is an autosomal dominant spinocerebellar degeneration that evolves to disability and death. Experimental data have shown that serotonin is an important cerebellar neurotransmitter and that impairment of the serotoninergic cerebellar system can induce cerebellar ataxia. OBJECTIVES: To evaluate the efficacy of fluoxetine, a serotonin reuptake inhibitor, in treating neurologic dysfunction in patients with MJD. PATIENTS AND METHODS: Thirteen MJD patients were treated with fluoxetine (20 mg/day) and were followed-up for 6 weeks. Outcome measures included functional capacity, standardized neurologic and cognitive ratings. The Montgomery-Asberg depression rating scale was used to control depressive symptoms. RESULTS: There was no significant improvement in motor abilities after 6 weeks of treatment. CONCLUSIONS: These results suggest that fluoxetine has no benefit in motor function of patients with MJD/SCA3.
Subject(s)
Fluoxetine/pharmacology , Motor Skills Disorders/drug therapy , Motor Skills Disorders/etiology , Selective Serotonin Reuptake Inhibitors/pharmacology , Adolescent , Adult , Cognition , Depression , Female , Fluoxetine/administration & dosage , Humans , Machado-Joseph Disease , Male , Middle Aged , Selective Serotonin Reuptake Inhibitors/administration & dosage , Treatment OutcomeABSTRACT
The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100beta, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100beta protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100beta protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100beta concentrations (p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100beta could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100beta release.
