Taku Ohkubo

Electroconvulsive therapy improves severe pain associated with fibromyalgia

Abstract The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper‐responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium‐99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck’s depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.

No genetic association between PCSK9 polymorphisms and Alzheimer's disease and plasma cholesterol level in Japanese patients.

SummaryGenetic mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene on the chromosome 1p cause susceptibility to autosomal dominant hypercholesterolemia (Abifadel et al., 2003; Leren, 2004; Timms et al., 2004). Variants of PCSK9 encoding neural apoptosis regulated convertase-1

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with senile plaques and contributes to Alzheimer’s disease (AD) pathology through oxidation-induced damage. MPO activity is normally higher in women than in men. Additionally, a functional biallelic (G/A) polymorphism in the promoter region (–463) of the MPO gene has been associated with a gender-specific risk factor for AD, but reports of this association have been inconsistent. Furthermore, estrogen is known to enhance MPO activity in myeloid cells and increases the amount of MPO in plasma. Recently, estrogen replacement therapy has been reported to reduce the risk of developing AD and to help maintain cognitive function in patients with AD. In the current study, we analyzed the MPO –463 polymorphism and two estrogen receptor-α polymorphisms in 205 Japanese sporadic AD patients and 92 controls. The results suggest that there is no significant difference in the genotypic frequencies and allelic frequencies of the MPO –463 polymorphism and the estrogen receptor-α polymorphisms between the Japanese sporadic AD group and the control group.

Genetic association between matrix metalloproteinase MMP-9 and MMP-3 polymorphisms and Japanese sporadic Alzheimer's disease.

Recent studies suggested that matrix metalloproteinases (MMPs) might play an important role in the pathophysiology of Alzheimers disease (AD). MMP-9 and MMP-3 are reported to degrade amyloid beta and have several functional polymorphisms associated with other common diseases. Four common polymorphisms in each of MMP-9 and MMP-3 were examined in AD cases and normal control individuals. Common polymorphisms of MMP-9, rs3918248, rs2664538, rs2250889 and rs2274756 showed no association with risk for AD. We observed strong linkage disequilibrium (LD) between rs2664538 and rs2250889 in our Japanese samples. The polymorphisms of MMP-3; 5A/6A insertion polymorphism in the promoter, rs3025079, rs520540 and rs679620 also did not influence risk for AD. LD of the 5A/6A polymorphism with rs679620 was relatively strong. These results suggest that the common polymorphisms of MMP-9 and MMP-3 investigated here are not associated with AD.

Lack of genetic association between cholesteryl ester transfer protein and Japanese sporadic Alzheimer’s disease

Background:  Cholesteryl ester transfer protein regulates the plasma high density lipoprotein cholesterol level, which is considered to play an antiatherogenic role in humans. The presence of apolipoprotein E epsilon4 allele is a strong risk factor for developing Alzheimer’s disease (AD). Since apolipoprotein E is a regulator of lipid metabolism, it is reasonable to assume that lipids play important roles in the pathogenesis of AD.

P1-294: Genetic association between PCSK9 and USF1 polymorphisms and Japanese Alzheimer’s disease and plasma cholesterol level

(p .001) Apo 3/ 3 genotype was found in 23.08% of the control group against 14.12% in the patients group (p .001). No statistical differences were found in the isoforms 3/ 4 and 2/ 4. No statistical relevance was found with the only individual with the 2/ 2 isoform. Conclusions: Genotype 4/ 4 of apolipoprotein E has a greater prevalence in patients with Alzheimer’s disease confirming our working hypothesis. There is an important association between ApoE 4 as risk factor of Alzheimer’s disease in addition to clinical and diagnosis skills.

No Genetic Association between ATP Binding Cassette Proteins and Japanese Sporadic Alzheimer’s Disease

The identification of the ε4 variant of apolipoprotein E as a genetic risk factor for late-onset Alzheimer’s disease (AD) suggests that cholesterol may play a direct role in the pathogenesis of the disease. Recent studies have suggested that the ATP-binding cassette (ABC) protein G5 (ABCG5) may be involved in the regulation of intestinal cholesterol absorption. Furthermore, genetic variation of this locus may affect blood cholesterol concentrations. We therefore studied whether the ABCG5 C1950G (Gln640Glu) polymorphism affects the risk of AD. In addition, there was no difference in mean baseline cholesterol concentrations between individuals with the C/C genotype and carriers of the G allele. Recent studies have shown that genetic regions including the ABCA12 gene might also be associated with the risk of AD. The ABCA12 gene, located <1 Mb from the peak marker on chromosome 2q34, is also a member of the ABC transporter superfamily. In the current study, two common polymorphisms of the ABCA12 gene, rs952718 (T/G) and rs956133 (A/G), were analyzed in our subjects. These polymorphisms showed no association with the risk of AD. Furthermore, we observed weak linkage disequilibrium between these two single nucleotide polymorphisms. These results indicate that the common polymorphisms of the ABCG5 and ABCA12 genes investigated here are not associated with AD.