Search

Noritake Hirota,1,2 Noboru Okamura1 1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Mukogawa Women’s University, Nishinomiya, Japan; 2General Incorporated Association Osaka Pharmaplan, Aozora Pharmacy, Osaka, JapanCorrespondence: Noritake HirotaGeneral Incorporated Association Osaka Pharmaplan, Aozora Pharmacy, 3-6-8 Nozato, Nishiyodogawa-Ku, Osaka City, Osaka 555-0024, JapanTel +81-6-6477-8088Fax +81-6477-8090Email n-hirota@faruma.co.jpPurpose: Despite the formal establishment of the Health Support Pharmacy system, few community pharmacies have transitioned to this new designation in Japan. Moreover, patients’ perspectives on the usefulness of health-support pharmacies and community pharmacies have not yet been investigated. In this work, we investigated patients’ attitudes, opinions, and awareness as users of member pharmacies of the Japan Federation of Democratic Medical Institutions (Min-Iren), with respect to two essential functions provided by community pharmacies—primary care and health support—to identify modern challenges facing community pharmacies.Methods: Regular visitors to participating Min-Iren community pharmacies were asked to complete an anonymous questionnaire. Responses were compared between users of health-support pharmacies and other pharmacy types, as well as between members and non-members of “collaborating organizations” (CO). CO is organizational partners of Min-Iren whose activities support affiliated facilities. Logistic regression analysis was performed to explore the predictive value of different factors on pharmacies’ primary-care and health-support functionality.Results: A total of 181 Min-Iren community pharmacies (51.7%: 181/350) participated in this study, and most patients answered the questionnaire (97.7%, n=2623). Relatively few patients recognized the term “Health Support Pharmacy” (12.2%). CO members tended to have a superior understanding of a wide variety of services provided by CPs as compared to non-members. Statistically significant predictors of primary-care and health-support functionality included male gender, having a primary-care pharmacist, age ≥ 60 years, recognition of the term “Health Support Pharmacy” and CO membership.Conclusion: CO members, a class of patients with a superior awareness of health promotion, demonstrated a good understanding of the variety of services provided by community pharmacies and tended to positively rate their pharmacy. Moving forward, efforts to raise awareness about the importance of health-promotional activities among community pharmacy users should further reinforce the primary-care and health-support functions of community pharmacies.Keywords: community pharmacy, health-support pharmacy, primary-care function, health-support function, patient awareness

Background and purpose: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. Methods: A total of 21 patients with polysomnography‐confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11C‐donepezil PET) and nigrostriatal dopaminergic function (18F‐DOPA PET). Clinical examination included the Movement Disorder Society–Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. Results: The 11C‐donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11C‐donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. Conclusion: Reduced neocortical 11C‐donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18F‐THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease‐related pathology in the brains of patients with CBS using positron emission tomography with 18F‐THK5351. Methods: Baseline and 1‐year follow‐up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18F‐THK5351 in 10 subjects: five patients with CBS and five age‐matched normal controls (NCs). Results: The 1‐year follow‐up scan images revealed that 18F‐THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18F‐THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18F‐THK5351 retention in the NCs. Conclusions: Longitudinal increases in 18F‐THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS. [ABSTRACT FROM AUTHOR]

Background and purpose Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy ( PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [18F] THK-5351, which we have recently developed. Methods Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [3H] THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [18F] THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed. Results Autoradiography in the brain sections of patients with PSP demonstrated [3H] THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [18F] THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP. Conclusions We conclude that [18F] THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein. [ABSTRACT FROM AUTHOR]

Objective: Three-dimensional stereotactic surface projection (3D-SSP) analyses have been widely used in dementia imaging studies. However, 3D-SSP sometimes shows paradoxical results on amyloid positron emission tomography (PET) analyses. This is thought to be caused by errors in anatomical standardization (AS) based on an (18)F-fluorodeoxyglucose (FDG) template. We developed a new method of 3D-SSP analysis for amyloid PET imaging, and used it to analyze (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) PET images of subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: The subjects were 20 with MCI, 19 patients with AD, and 17 healthy controls. Twelve subjects with MCI were followed up for 3 years or more, and conversion to AD was seen in 6 cases. All subjects underwent PET with both FDG and BF-227. For AS and 3D-SSP analyses of PET data, Neurostat (University of Washington, WA, USA) was used. Method 1 involves AS for BF-227 images using an FDG template. In this study, we developed a new method (Method 2) for AS: First, an FDG image was subjected to AS using an FDG template. Then, the BF-227 image of the same patient was registered to the FDG image, and AS was performed using the transformation parameters calculated for AS of the corresponding FDG images. Regional values were normalized by the average value obtained at the cerebellum and values were calculated for the frontal, parietal, temporal, and occipital lobes. For statistical comparison of the 3 groups, we applied one-way analysis of variance followed by the Bonferroni post hoc test. For statistical comparison between converters and non-converters, the t test was applied. Statistical significance was defined as p < 0.05. Results: Among the 56 cases we studied, Method 1 demonstrated slight distortions after AS of the image in 16 cases and heavy distortions in 4 cases in which the distortions were not observed with Method 2. Both methods demonstrated that the values in AD and MCI patients were significantly higher than those in the controls, in the parietal, temporal, and occipital lobes. However, only Method 2 showed significant differences in the frontal lobes. In addition, Method 2 could demonstrate a significantly higher value in MCI-to-AD converters in the parietal and frontal lobes. Conclusions: Method 2 corrects AS errors that often occur when using Method 1, and has made appropriate 3D-SSP analysis of amyloid PET imaging possible. This new method of 3D-SSP analysis for BF-227 PET could prove useful for detecting differences between normal groups and AD and MCI groups, and between converters and non-converters. [ABSTRACT FROM AUTHOR]

While considerable effort has focused on developing positron emission tomography β-amyloid imaging radiotracers for the early diagnosis of Alzheimer's disease, no radiotracer is available for the non-invasive quantification of tau. In this study, we detail the characterization of (18)F-THK523 as a novel tau imaging radiotracer. In vitro binding studies demonstrated that (18)F-THK523 binds with higher affinity to a greater number of binding sites on recombinant tau (K18Δ280K) compared with β-amyloid(1-42) fibrils. Autoradiographic and histofluorescence analysis of human hippocampal serial sections with Alzheimer's disease exhibited positive THK523 binding that co-localized with immunoreactive tau pathology, but failed to highlight β-amyloid plaques. Micro-positron emission tomography analysis demonstrated significantly higher retention of (18)F-THK523 (48%; P < 0.007) in tau transgenic mice brains compared with their wild-type littermates or APP/PS1 mice. The preclinical examination of THK523 has demonstrated its high affinity and selectivity for tau pathology both in vitro and in vivo, indicating that (18)F-THK523 fulfils ligand criteria for human imaging trials. [ABSTRACT FROM AUTHOR]

Aim: To determine early brain changes in the distribution of an amyloid positron emission tomography (PET) probe, 11C-labeled BF-227 or [11C]BF-227, in order to accurately predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). Patients and Methods: Amyloid plaque burden was evaluated using [11C]BF-227 PET in AD, MCI and aged normal controls. A voxel-based analysis of [11C]BF-227 PET images was performed to characterize the culprit brain lesion in patients with MCI who were destined to progress to AD, referred to as MCI converters (MCI-C). In addition, binding characteristics of BF-227 to amyloid deposits were examined using postmortem AD brain samples. Results: Voxel-based statistical analyses of the BF-227 PET images clearly demonstrated an abnormal distribution of BF-227 mainly in the posterior association area in MCI-C and patients with AD. BF-227 uptake in the lateral temporal cortex was consistently observed in almost all MCI-C and patients with AD, and it distinguished MCI-C from MCI nonconverters. BF-227 binding strongly correlated with dense amyloid-β protein plaque density, but not with diffuse plaque density in the frontal cortex. Conclusion: BF-227 uptake in the lateral temporal cortex is a reliable indicator that can be used for predicting prognosis in patients with MCI. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains. [ABSTRACT FROM AUTHOR]

To understand the real cause of stabilization of the third state and to assure the possible application of the tristable switching, we have studied the effect of chiral centers on the appearance of the third state, synthesizing (R)-(+)- and (S)-(2)-4-(1-trifluoromethylalkoxy(n)carbonyl) phenyl 4′-alkoxy(m)biphenyl-4-carboxylate [This symbol cannot be converted into ASCII text] where m=8, 9, 10, or 12 and n=6 or 8; note that the chiral centre has a trifluoromethyl group. By observing light transmittance and switching current responses to a triangular voltage wave and by taking stroboscopic micrographs, we have confirmed that all the materials synthesized show the tristable switching in wide temperature ranges; in particular, the materials with m=10 or 12 and n=6 have the stabilized third state even at temperatures below 30°C. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbance is one of the major and unsolved problems in older people. Most of the previous sleep studies rely on self-reported documents, and memory disturbance in older people might bias sleep complaints and health status.Objective: Sleep disturbances were studied as a mortality risk.Methods: In 272 patients who were aged, infirmed and chronically institutionalized in a skilled-care geriatric hospital, the presence or absence of sleep disturbances were examined by hourly observations of patients over 2 weeks at baseline, and they were prospectively followed up for 2 years to assess mortality.Results: Mortality after 2 years was significantly higher in the nighttime insomnia, daytime sleepiness, and sleep-onset delay groups. Further, adjusted for age, gender and activities of daily living status, the presence of nighttime insomnia and sleep-onset delay remained associated with a higher risk of mortality.Conclusion: Sleep disturbance may be one of the symptoms indicating poor health or functional deficits, and be an independent risk factor for survival. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) is a plasma protein that plays an important role in cholesterol transport. The protein exists in 3 different isoforms coded for by alleles ε2, ε3 and ε4. Recent studies have shown that the frequency of the APOE ε4 allele is much greater among individuals with Alzheimer's disease than age-matched healthy controls [an approximate 4-fold increase (36.6 vs 9.4%) in one recent study]. However, due to an insufficient sensitivity of the APOE ε4 allele in detecting patients with Alzheimer's disease and the presence of this allele in demented and nondemented individuals, APOE genotyping should not be used alone as a sole diagnostic test for Alzheimer's disease. An additional recent finding is that central muscarinic receptor binding, as revealed by positron emission tomography (PET) and [C]benztropine, declines with the progression of Alzheimer's disease regardless of the presence or absence of APOE ε4 allele. These findings suggest that measures of acetylcholine neurotransmission in the living Alzheimer's disease brain by PET help to visualise altered cholinergic function during the clinical course of Alzheimer's disease and to identify appropriate individuals who are more likely to respond to emerging cholinergic interventions. [ABSTRACT FROM AUTHOR]