Comparison of the binding characteristics of [18F]THK-523 and other amyloid imaging tracers to Alzheimer��s disease pathology

Purpose

Extensive deposition of senile plaques and neurofibrillary tangles in the brain is a pathological hallmark of Alzheimer??s disease (AD). Although several PET imaging agents have been developed for in vivo detection of senile plaques, no PET probe is currently available for selective detection of neurofibrillary tangles in the living human brain. Recently, [¹⁸F]THK-523 was developed as a potential in vivo imaging probe for tau pathology. The purpose of this study was to compare the binding properties of [¹⁸F]THK-523 and other amyloid imaging agents, including PiB, BF-227 and FDDNP, to synthetic protein fibrils and human brain tissue.

Methods

In vitro radioligand binding assays were conducted using synthetic amyloid ??₄₂ and K18??K280-tau fibrils. Nonspecific binding was determined by the addition of unlabelled compounds at a concentration of 2???M. To examine radioligand binding to neuropathological lesions, in vitro autoradiography was conducted using sections of AD brain.

Results

[¹⁸F]THK-523 showed higher affinity for tau fibrils than for A?? fibrils, whereas the other probes showed a higher affinity for A?? fibrils. The autoradiographic analysis indicated that [¹⁸F]THK-523 accumulated in the regions containing a high density of tau protein deposits. Conversely, PiB and BF-227 accumulated in the regions containing a high density of A?? plaques.

Conclusion

These findings suggest that the unique binding profile of [¹⁸F]THK-523 can be used to identify tau deposits in AD brain.     

Redo surgery for biliary atresia

The Kasai redo surgery is important for treating biliary atresia. In the era of liver transplantation (LTx), pediatric surgeons must accurately select patients for redo surgery and ensure that potential LTx can be performed later. Although optimal timing for redo varies among cases, appropriate timing is essential. We reviewed the significance, optimal timing, operative procedures, and indications of Kasai redo surgery. Between 1989 and 2011, 2,630 patients were registered in the Japanese Biliary Atresia Registry (JBAR), and the data collected from JBAR regarding Kasai redo surgery were analyzed. Patients were divided into two groups, Group 1 (1989–1999, n = 1,423) and Group 2 (2000–2011, n = 1,207). The redo incidence significantly reduced in Group 2. Although no significant difference was found in the native liver jaundice-free survival rates between the two groups, the overall survival rate at initial registry was significantly higher in Group 2. This may be because of the limited number of patients selected for redo and increased availability of early LTx. Patients who achieved sufficient bile drainage following the initial Kasai surgery but developed sudden bile flow cessation were the best candidates for Kasai redo surgery; it should be performed only once for this subset.     

Estrogen receptor‐β gene polymorphism and colorectal cancer risk: Effect modified by body mass index and isoflavone intake

Estrogen receptor (ER)‐β signaling has generally been implicated in protection against colorectal cancer. The ER‐β gene cytosine‐adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community‐based case‐control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein‐labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age‐adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m^?2) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism.     

Effect of bruxism-like activity on the salivary Chromogranin A as a stress marker

Summary  The aim of this study was to determine whether measuring salivary chromogranin A (CgA) is useful in assessing individual stress levels and whether bruxism-like activity influences the salivary CgA level. From 44 adult healthy volunteers, we collected saliva samples with and without a stress condition (loud unpleasant sound). We assayed salivary samples with an ELISA to determine the content of CgA. We investigated also the effect of bruxism-like activity on salivary CgA production during stress. There were three patterns (group A, B, C) of response to the stressor on salivary CgA. They showed different responses and different effects of bruxism-like activity. This study shows the possibility of evaluating stress levels of individuals by measuring salivary CgA. Salivary CgA responds to psychosomatic stress. Bruxism-like activity prevented a stress-induced increase of salivary CgA in group A and B (75% of subjects), suggested that the reaction of the sympathetic-adrenomedullary system is regulated by the bruxism-like activity of the masticatory organ. The effect of bruxism-like activity in group C (high baseline of salivary CgA) was different from the effect in group A and B. Correspondence: S. Sato, Dept. of Craniofacial Growth Development Dentistry, Division Orthodontics, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, 238-8580 Japan     

The involvement of bradykinin in adrenaline-induced pulmonary edema in rats

We investigated the effect of endogenous bradykinin on adrenaline-induced pulmonary edema (PE) by blocking bradykinin receptors. In preliminary experiments, a bolus injection of adrenaline (ADR; 10 microg/kg) solution (10 microg/ml) was determined to be an edematogenic dose for inducing PE. The lung body weight index (LBI) and incidence of PE (IPE) were determined. The IPE and LBI of the group pretreated with Des-Arg9-[Leu8]-Bradykinin (DA-BK, 50 microg/kg, 50 microg/ml) increased significantly compared with those of the control group (p<0.05). On the other hand, there were no remarkable changes in IPE and LBI in the groups pretreated with Hoe140 (D-Arginyl-[Hyp3, Thi5, D-Tic7, Oic8]-Bradykinin (100 microg/kg, 100 microg/ml), captopril (20 mg/kg, 20 mg/ml) or L-NAME (1 mg/kg, 1 mg/ml). Moreover, the IPE and LBI of the group co-treated with L-NAME and DA-BK decreased compared with the DA-BK group (p<0.05). Thus, bradykinin aggravates adrenaline-induced PE through activation of the B2 receptor by the kallikreins as a result of the ADR administration, although the precise mechanism is not known.     

Clinical Evaluation of protocol for the craniomandibular disorders. 1. Protocol of our department

Craniomandibular disorders are conditions encompassing various types of dysfunction of the stomatognathic system. To define the very nature of morbidity, both differential and pathological diagnosis are absolutely necessary. At present, each medical institution in this country has its own protocol for evaluating and treating craniomandibular disorders. This makes it difficult to exchange and compare data between institutions. In this paper, a protocol worked out by our department after a series of clinical tests and study is presented, and its merits and unresolved problems are discussed.