Panic disorder (PD) is the repeated sudden occurrence of panic attacks, episodes characterized by psychological symptoms. Peripheral benzodiazepine receptor (PBR) is closely associated with personality traits for anxiety tolerance, and that it holds promise as a biological marker of stressful conditions. We have performed association analyses using the polymorphism to determine the PBR in PD. We screened the subjects for sequence variations within the 5' region, the coding region (exons 2-4), and the 3' noncoding region. One novel missense variant in exon 4, derived from the nucleotide transition in codon 162 (CGT --> CAT:485G > A) resulting in an arginine-to-histidine (Arg --> His) change, was detected in these subjects. The 485G > polymorphism of the PBR gene was analyzed in 91 PD patients and 178 controls. The genotypic and allelic analyses of the 485G > A revealed significant differences between the panic patients and the comparison subjects (P = 0.021 and 0.014, respectively). The present study provides new and important evidence that variation in the PBR gene influences susceptibility to PD.
MR images of the neck were prospectively studied in 19 patients with hyperparathyroidism. Fast low angle shot (FLASH) sequence was performed in addition to T1- and T2-weighted spin echo (SE) sequences. FLASH images were obtained with 320/12/20 degrees (TR/TE/flip angle) using presaturation technique. TE of 12 ms was chosen to eliminate high signal of fat tissue. In the evaluation of detectability, a combination of T1-weighted SE and FLASH images (T1WI + FLASH) was compared with a combination of T1- and T2-weighted SE images (T1WI + T2WI). MR imaging correctly depicted 20 of 30 abnormal glands on both T1WI + FLASH and T1WI + T2WI. FLASH imaging effectively eliminated high signal of fat tissue. Nineteen abnormal glands demonstrated higher signal than surrounding tissues on FLASH images, whereas 12 glands were high-intense on T2-weighted SE images. We conclude that FLASH imaging provides improved tissue contrast and anatomic delineation and, thus, may replace T2-weighted SE imaging in the neck.
A bstract : Piracetam and structurally related nootropics are known to potentiate the anticonvulsant effects of antiepileptic drugs. It remains to be seen, however, whether these nootropics inhibit proconvulsant actions of many toxic agents including Ro 5‐4864, a specific agonist for peripheral‐type benzodiazepine receptors (PBR). The present study was designed to address this issue using EL mice, an animal model of epilepsy. In behavioral pharmacological experiments, EL mice were highly susceptible to convulsions induced by Ro 5‐4864 (i.p.) in comparison with nonepileptic DDY mice. Nefiracetam administered orally to EL mice inhibited spontaneous seizures. In DDY mice, convulsions induced by Ro 5‐4864 were prevented by nefiracetam when administered by i.v. injection. Aniracetam (i.v.) was partially effective, but piracetam and oxiracetam were ineffective as anticonvulsants. Binding assay for brain tissues revealed a higher density of mitochondrial PBR in EL mice compared with DDY mice. Binding of the PBR ligands Ro 5‐4864 to either EL or DDY mouse brain was inhibited by micromolar concentrations of these nootropic agents in the sequence of nefiracetam > aniracetam ≫ oxiracetam, piracetam. This rank order is identical to potency as anticonvulsants. These data suggest that nefiracetam may prevent toxic effects of PBR agonists through interacting with PBR.
We have reported that cyclins and the corresponding cyclin-dependent kinase (CDK) family are related to cell proliferation during development as well as epileptogenesis. In the present study, we used EL mice to examine how levetiracetam (Lev) controls the altered expressions of cyclins and the CDK family during development, and further, the epileptogenesis as well in the parietal cortex, the seizure initiation site of EL. Developmental changes in the expression of cyclin and the corresponding CDK families (cyclin D⁄CDK-4, cyclin E⁄CDK-2, cyclin A⁄CDK-2, cyclin A⁄CDK-1, and cyclin B⁄CDK-1) in the parietal cortex of EL mice and the control DDY mice were examined by Western blotting. At different ages, one group of mice (n = 6) were administered a single dose of Lev 160 mg/kg Lev p.o. and a treatment naïve group (n = 6) was administered vehicle, three days before sacrifice. Compared with the control DDY mice, treatment naïve EL mice showed upregulations of cell cycle-specific cyclins⁄CDK during the early developmental stages, suggesting that reentry into cell cycle is promoted prior to the beginning of seizures. Lev abolished these effects and Lev-treated EL mice showed no seizures at all. These results suggest that cyclins⁄CDK may be activated during early stages of development before exhibiting seizures, suggesting that reentry into cell cycle in the parietal cortex is a candidate mechanism for the seizure predisposition of EL mice. The antiepileptic effects of Lev may be related to regulation of cell cycle reentry.
Abstract: Piracetam‐like nootropics (or cognitive enhancers) have been used for the treatment of various forms of dementia, including Alzheimer's disease. The underlying mechanisms of their actions, however, are largely unknown. Our recent studies have demonstrated that nefiracetam, a nootropic agent, can markedly enhance activities of neuronal L‐and N‐type (α 1B ) Ca 2+ channels as well as those of presynaptic nicotinic acetylcholine (ACh) receptors, thereby increasing neurotransmitter release. Aniracetam exerted a slight facilitatory effect on Ca 2+ channels, but no effect on nicotinic ACh receptors. Piracetam and oxiracetam have no such actions on Ca 2+ channels and nicotinic ACh receptors. It is suggested that inhibitory G‐proteins (Go/Gi) and protein kinase A (PKA) mediate the nefiracetam action on Ca 2+ channels, whereas protein kinase C (PKC) mediates the drug action on nicotinic ACh receptors. In the hippocampus of the rodent, nefiracetam induces a long‐lasting (>4 h) facilitation of synaptic transmission. The ‘LTP‐like’ facilitation appears to result from activation of presynaptic nicotinic ACh receptors (and Ca 2+ channels as well) by nefiracetam. In conclusion, nefiracetam is distinguished from other nootropic agents for its preferential actions on both presynaptic Ca 2+ channels and nicotinic ACh receptors, and could therefore be of great therapeutic importance to the neurotransmission failure that contributes to the symptoms of Alzheimer's disease and associated disorders.
