ABSTRACT
Iron porphyrins are known to provide CH4 as an eight-electron reduction product of CO2 in a photochemical reaction. However, there are still some aspects of the reaction mechanism that remain unclear. In this study, we synthesized iron porphyrin dimers and carried out the photochemical CO2 reduction reactions in N,N-dimethylacetamide (DMA) containing a photosensitizer in the presence of 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole (BIH) as an electron donor. We found that, despite a low catalytic turnover number, CH4 was produced only when these porphyrins were facing each other. The close proximity of the cyclic dimers, distinguishing them from a linear Fe porphyrin dimer and monomers, induced multi-electron CO2 reduction, emphasizing the unique role of their structural arrangement in CH4 formation.
ABSTRACT
A series of rigid and conformationally restricted cyclic bis(zinc porphyrin)s connected via 2,2'-bipyridine and phthalamide, isophthalamide, or terephthalamide moieties were prepared by metal-templated synthesis. The yields were significantly improved when compared with those obtained under metal-free conditions. In particular, phthalamide and terephthalamide derivatives were obtained only by metal-templated synthesis. Structural analyses and dynamics of the exchange between the conformers in each cyclic porphyrin were examined by NMR spectroscopy. Although the distances between the two zinc porphyrins were extended in the order of phthalamide, isophthalamide, and terephthalamide derivatives, the order of the specific retention of the cyclic porphyrins on cyanopropyl-modified silica gel (CN-MS) chromatography columns varied. Thus, this order was reversed in the isophthalamide and terephthalamide derivatives. Based on the rigid structure of the terephthalamide derivative, the origin of the specific retention on the CN-MS chromatography column was attributed to both the distance and rigidity of the cyclic porphyrins.
ABSTRACT
Anhedonia is one of the non-motor symptoms observed in the Parkinson's disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p=0.03 and p=0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinson's disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I-IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.
Subject(s)
Anhedonia/physiology , Depression/epidemiology , Depression/etiology , Parkinson Disease , Aged , Aged, 80 and over , Cohort Studies , Cross-Sectional Studies , Female , Humans , Japan , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/epidemiology , Parkinson Disease/psychology , Psychiatric Status Rating Scales , Severity of Illness IndexABSTRACT
BACKGROUND: Pain is a frequent, troublesome symptom of PD but is under-recognized and poorly understood. AIM: We characterized pain prevalence, severity, and location in PD, to better understand its pathophysiology and improve diagnosis and treatment. SUBJECTS AND METHODS: A cross-sectional controlled study was conducted at 19 centers across Japan. A total of 632 subjects with Mini-Mental State Examination scores ≥24 were enrolled, including 324 PD patients and 308 controls. Sex and mean age did not differ between the two groups. Demographic and clinical data were collected. Pain was assessed using questionnaires, the SF-36v2 bodily pain scale, and a body illustration for patients to indicate the location of pain in 45 anatomical areas. RESULTS: Pain prevalence in the PD group was 78.6%, significantly higher than in controls (49.0%), as was its severity. There was no correlation between SF-36v2 score and motor scores, such as Unified Parkinson's Disease Rating Scale III or Hoehn & Yahr scores. Pain distribution was similar between groups, predominantly in the lower back, followed by the gluteal region, lower legs, thighs, posterior neck, and shoulders. CONCLUSION: Pain is a significant problem in the Japanese PD population and we discuss its pathophysiology.
Subject(s)
Pain/etiology , Parkinson Disease/complications , Parkinson Disease/epidemiology , Aged , Aged, 80 and over , Female , Health Surveys , Humans , Japan/epidemiology , Male , Middle Aged , Severity of Illness Index , Statistics, NonparametricABSTRACT
We herein report that the clinical, laboratory, and radiographic features and positron emission tomography (PET) imaging may provide valuable clues to the pathogenesis of cerebral amyloid angiopathy (CAA)-associated encephalopathy, which currently remains unclear. We herein describe two cases of encephalopathy with CAA, with an emphasis on PET imaging with (11)C-Pittsburgh compound B ((11)C-PiB) and (18)F-fluorodeoxyglucose ((18)F-FDG). One case of Alzheimer's disease for which a brain biopsy was performed showed CAA-related inflammation. Another case that had developed sudden sensory aphasia presented with posterior reversible encephalopathy syndrome-like vasogenic edema in the left temporal region with (11)C-PiB uptake and microhemorrhages. (11)C-PiB and (18)F-FDG PET are useful for detecting CAA-associated encephalopathy, including atypical CAA cases.
Subject(s)
Benzothiazoles , Cerebral Amyloid Angiopathy/diagnostic imaging , Positron-Emission Tomography/methods , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Aged , Aniline Compounds , Carbon Radioisotopes , Cerebral Amyloid Angiopathy/complications , Diagnosis, Differential , Humans , Male , Posterior Leukoencephalopathy Syndrome/etiology , ThiazolesABSTRACT
A 44-year-old woman with a history of transient right hemiparesis presented with personality change. One year later, she was admitted with ophthalmoparesis, dysarthria and regression phenomenon. MRI indicated acute infarction of the paramedian region of the midbrain and a nodular lesion in the interpeduncular fossa with contrast enhancement. Two years later, the patient was admitted with sudden onset of right hemiplegia. MRI showed acute infarction in the left side of the pons, diffuse brain atrophy, and abnormal contrast enhancement in the nodular lesion of interpeduncular fossa and leptomeninges of the ventral pons. MR angiography revealed that cerebral main tracts were intact, and cerebrospinal fluid analysis revealed mild pleocytosis and slightly elevated protein levels. Cervical lymph node biopsy demonstrated caseating granuloma with acid-fast bacilli. The patient was diagnosed with chronic tuberculous meningitis, even though tuberculous bacilli were not detected on polymerase chain reaction (PCR) or in culture. Antituberculous medication resulted in radiological resolution and neurological improvement. Although the patient had mild headache and pyrexia at the first admission, no signs of meningeal irritation were confirmed throughout the clinical course. We suspect that a paucity of tuberculous bacilli released from the tuberculous foci in the meninges to the subarachnoid space caused prolonged clinical course and lack of meningeal irritation signs.
Subject(s)
Brain Stem Infarctions/diagnosis , Brain Stem Infarctions/etiology , Tuberculosis, Meningeal/complications , Tuberculosis, Meningeal/diagnosis , Adult , Antitubercular Agents/administration & dosage , Brain Stem Infarctions/pathology , Chronic Disease , Female , Humans , Lymph Nodes/pathology , Magnetic Resonance Imaging , Neck , Recurrence , Treatment Outcome , Tuberculosis, Meningeal/drug therapy , Tuberculosis, Meningeal/pathologyABSTRACT
BACKGROUND: In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD). OBJECTIVE: We evaluated whether vitamin D3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups. DESIGN: Patients with PD (n = 114) were randomly assigned to receive vitamin D3 supplements (n = 56; 1200 IU/d) or a placebo (n = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D3 group: -0.38 ± 0.48 (P = 0.91); change within placebo group, +0.63 ± 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D3 group: ±0.00 ± 0.60 (P = 0.78); change within placebo group: +0.37 ± 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II. CONCLUSION: Vitamin D3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841.
Subject(s)
Cholecalciferol/administration & dosage , Dietary Supplements , Parkinson Disease/drug therapy , Aged , Blood Pressure , Body Mass Index , Calcium, Dietary/blood , Cholecalciferol/blood , Disease Progression , Double-Blind Method , Endpoint Determination , Female , Follow-Up Studies , Genotype , Humans , Male , Middle Aged , Parathyroid Hormone/blood , Parkinson Disease/genetics , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Surveys and QuestionnairesABSTRACT
We report a case of isolated hypoglossal nerve palsy with acute lymphoblastic leukemia. A 47-year-old woman had fever unknown origin during two months. Her tongue bent to the right and cephalalgia developed. She complained unable to speech and swallow. On admission, right isolated hypoglossal nerve palsy presented. Blood examination showed the mild elevation of CRP and soluble IL2 receptor. Examination of cerebrospinal fluid was negative. Gadolinium enhanced magnetic resonance imaging (MRI) of brain showed abnormal intensity on sphenoid bone. 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) showed abnormal accumulation on sphenoid bone, spleen, the left supraclavicular node, mesenteric lymph node. Blast cells appeared in peripheral blood afterwards. Acute lymphatic leukemia (ALL) was diagnosed by bone marrow biopsy. The central nervous system disorder by ALL tends to the invasion to meninges or cerebrovascular disorder. This is the first case report that isolated hypoglossal nerve paralysis resulted from ALL.
Subject(s)
Hypoglossal Nerve Diseases/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Female , Humans , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosisABSTRACT
A 20-year-old female patient was presented with a 1-year history of progressive weakness of the left hand. Examination on admission showed atrophy of the muscles of the left forearm, cold paralysis and minipolymyoclonus. MR images of the cervical cord showed anterior transfer of the cervical cord on anterior flexion and cervical cord compression at the site of cervical kyphosis, confirming the diagnosis of Hirayama disease. Many features of the present case are unusual: the patient is a female (who are rarely afflicted by this disease), with cervical kyphosis and a history of exercise involving cervical vertebral loading, suggesting a potential involvement of the latter two factors in the disease onset. The findings suggest that cervical vertebral dysplasia and intervertebral disc degeneration may influence cervical kyphosis, and be involved in the onset of Hirayama disease.
Subject(s)
Cervical Vertebrae/pathology , Intervertebral Disc Degeneration/complications , Intervertebral Disc/pathology , Kyphosis/complications , Spinal Cord Compression/etiology , Spinal Diseases/complications , Spinal Muscular Atrophies of Childhood/complications , Adult , Arm , Exercise , Female , Humans , Muscle, Skeletal , Muscular Atrophy , Myoclonus , Neck/pathology , Paralysis , Spinal Cord/pathology , Stress, Mechanical , Young AdultABSTRACT
We aimed to examine associations among serum 25-hydroxyvitamin D levels, 1,25-dihyroxyvitamin D levels, vitamin D receptor polymorphisms, vitamin D binding protein gene polymorphisms, and the severity of Parkinson's disease. In 137 patients, the severity of Parkinson's disease was evaluated using Hoehn & Yahr stage and Unified Parkinson's Disease Rating Stage by neurologists and compared with 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, vitamin D receptor polymorphisms, ie, FokI (rs10735810), BsmI (rs1544410), Cdx2 (rs11568820), ApaI (rs7976091), and TaqI (rs731236), and vitamin D binding protein gene polymorphisms GC1 (rs7041)/GC2 (rs4588) in a cross-sectional study. Mean ± standard deviation levels of 25-hydroxyvitamin D were 21.1 ± 9.0 ng/mL. Levels were deficient (<20 ng/mL) in 49% of patients. In contrast, 1,25-hydroxyvitamin D levels were considered normal in all patients. Higher circulating 25-hydroxyvitamin D levels were significantly associated with milder Parkinson's disease evaluated by Hoehn & Yahr stage (P = .002) and total Unified Parkinson's Disease Rating Stage (P = .004) even after multivariate adjustment for 8 covariates, including disease duration. However, significant associations were not observed in 1,25-hydroxyvitamin D levels. Under multivariate analysis with 25-hydroxyvitamin D as well as other 8 covariates including disease duration, carriers of vitamin D receptor FokICC genotype had a milder form of Parkinson's disease: odds ratio, 0.32; 95% confidence interval, 0.16 to 0.66, P = 0.002. These results suggest that higher 25-hydroxyvitamin D levels and the vitamin D receptor FokICC genotype may be independently associated with milder forms of Parkinson's disease. However, significant associations were not observed in 1,25-hydroxyvitamin D levels.
Subject(s)
Genetic Predisposition to Disease , Parkinson Disease/genetics , Polymorphism, Genetic , Receptors, Calcitriol/genetics , Vitamin D/analogs & derivatives , Aged , Aged, 80 and over , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Parkinson Disease/blood , Severity of Illness Index , Vitamin D/blood , Vitamin D/geneticsSubject(s)
Herpes Zoster/etiology , Myelitis/complications , Myelitis/pathology , Spinal Cord/pathology , Female , HumansABSTRACT
BACKGROUND: Progressive supranuclear palsy (PSP) and parkinsonian variant of multiple system atrophy (MSA-P) are clinically difficult to differentiate from idiopathic Parkinson's disease (PD), particularly in the early stages of the disease. Previous reports indicated that the olfactory function is relatively intact or slightly reduced in patients with PSP and MSA-P, suggesting that the odor stick identification test for Japanese (OSIT-J), which is a short and simple noninvasive test that is potentially useful clinically for detecting early-stage PD in Japan, may be useful in the differential diagnosis of early-stage PD from MSA-P and PSP. There is no information on the sensitivity and specificity of OSIT-J in the diagnosis of parkinsonian syndromes such as PSP and MSA-P. METHODS: We assessed the olfactory function using the OSIT-J test in 94 Japanese patients with idiopathic PD, 15 with MSA-P, 7 with PSP, and 29 age-matched control subjects. RESULTS: The mean ± SD score of OSIT-J in patients with PD (4.4 ± 2.9) was significantly lower than in patients with MSA-P (8.7 ± 2.2, P < 0.0001), PSP (7.6 ± 2.2, P < 0.0057), and control subjects (10.5 ± 1.3, P < 0.0001). The area under the curve (AUC) of receiver operating characteristic (ROC) to discriminate PD from normal control using OSIT-J scores was 0.97 (95% confidence interval, 0.95-1.00), from MSA-P 0.87 (0.80-0.95), and from PSP 0.81 (0.66-0.96). CONCLUSION: The OSIT-J is a potentially useful clinical test not only for detection of olfactory deficit in PD but also for differentiating PD from MSA-P and PSP.
Subject(s)
Multiple System Atrophy/diagnosis , Olfaction Disorders/diagnosis , Olfaction Disorders/ethnology , Parkinson Disease/diagnosis , Supranuclear Palsy, Progressive/diagnosis , Aged , Asian People , Diagnosis, Differential , Discriminant Analysis , Female , Humans , Male , Odorants/analysis , Olfaction Disorders/etiology , Parkinson Disease/complications , ROC Curve , Sensitivity and SpecificityABSTRACT
Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.
Subject(s)
Corpus Striatum/diagnostic imaging , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography/methods , Receptor, Adenosine A2A/metabolism , Xanthines , Aged , Antiparkinson Agents/therapeutic use , Corpus Striatum/metabolism , Dyskinesias/complications , Dyskinesias/diagnostic imaging , Dyskinesias/drug therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Models, Biological , Parkinson Disease/complications , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Prognosis , Receptor, Adenosine A2A/analysis , Receptor, Adenosine A2A/physiologyABSTRACT
The Positron Medical Center has developed a large number of radiopharmaceuticals and 36 radiopharmaceuticals have been approved for clinical use for studying aging and geriatric diseases, especially brain functions. Positron emission tomography (PET) has been used to provide a highly advanced PET-based diagnosis. The current status of the development of radiopharmaceuticals, and representative clinical and methodological results are reviewed.
Subject(s)
Alzheimer Disease/diagnostic imaging , Positron-Emission Tomography , Brain/blood supply , Glucose/metabolism , Humans , Muscle, Skeletal/diagnostic imaging , Parkinsonian Disorders/diagnostic imaging , Radiopharmaceuticals , Receptor, Adenosine A1/physiology , Receptor, Adenosine A2A/physiology , Receptors, Purinergic P1/physiology , Receptors, sigma/physiology , Regional Blood FlowABSTRACT
Our efforts to optimize prototype opioid receptor-like 1 (ORL1) antagonist 1 led to the discovery of 4-{3-[(2R)-2,3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine 10. 10 showed potent ORL1 antagonistic activity, excellent selectivity over other opioid receptors, and in vivo efficacy after oral dosing. Currently clinical trials of 10 are underway.
Subject(s)
Benzimidazoles/administration & dosage , Benzimidazoles/pharmacology , Narcotic Antagonists , Piperidines/administration & dosage , Piperidines/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Administration, Oral , Animals , Benzimidazoles/metabolism , Benzimidazoles/pharmacokinetics , CHO Cells , Cricetinae , Cricetulus , Humans , Hydrophobic and Hydrophilic Interactions , Inhibitory Concentration 50 , Mice , Piperidines/metabolism , Piperidines/pharmacokinetics , Rats , Receptors, Opioid/metabolism , Structure-Activity Relationship , Nociceptin ReceptorABSTRACT
Following the discovery of 5-chloro-6-[piperazin-1-yl]-1H-benzimidazole as a novel pharmacophore for potent and selective ORL1 antagonist activity, optimization of this new lead by introduction of a methyl substitution on the piperazine ring resulted in a highly potent and selective, orally available, and brain penetrable ORL1 antagonist, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole. Stereochemistry of the methyl substituent on the piperazine ring to control the functional activity of other opioid receptors is also described.
Subject(s)
Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Brain/drug effects , Narcotic Antagonists , Administration, Oral , Animals , Benzimidazoles/chemistry , Combinatorial Chemistry Techniques , Haplorhini , Humans , Mice , Molecular Structure , Rats , Receptors, Opioid , Structure-Activity Relationship , Nociceptin ReceptorABSTRACT
Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is structurally distinct from conventional non-peptide antagonists known to date.
Subject(s)
Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Narcotic Antagonists , Benzimidazoles/chemistry , Combinatorial Chemistry Techniques , Humans , Molecular Structure , Receptors, Opioid , Structure-Activity Relationship , Nociceptin ReceptorABSTRACT
A simultaneous evaluation of presynaptic and postsynaptic dopaminergic positron emission tomography markers, the dopamine transporters and the dopamine D2-like receptors, was performed in eight patients with parkinsonian phenotype of multiple system atrophy. Both presynaptic and postsynaptic markers were revealed to have declined in such a manner that they kept strong positive correlation throughout the striatum of all patients, suggesting that the degeneration process in the striatum may involve the entire structure of the dopaminergic synapse. In two L-3,4,dihydroxyphenyl-alanine-responsive cases, the balance of decline in two markers was relatively shifted to presynaptic dominant side. Correlative positron emission tomography study of presynaptic and postsynaptic dopaminergic function may be useful for the diagnosis of multiple system atrophy and to understand the mechanisms of its temporal L-3,4,dihydroxyphenyl-alanine responsiveness.
Subject(s)
Corpus Striatum/metabolism , Dopamine/metabolism , Multiple System Atrophy/metabolism , Substantia Nigra/metabolism , Synapses/metabolism , Aged , Biomarkers/analysis , Biomarkers/metabolism , Corpus Striatum/diagnostic imaging , Corpus Striatum/physiopathology , Dendrites/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Female , Humans , Levodopa/pharmacology , Male , Middle Aged , Multiple System Atrophy/diagnostic imaging , Multiple System Atrophy/physiopathology , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Neural Pathways/physiopathology , Positron-Emission Tomography , Predictive Value of Tests , Presynaptic Terminals/metabolism , Receptors, Dopamine D2/metabolism , Substantia Nigra/diagnostic imaging , Substantia Nigra/physiopathology , Synaptic Transmission/drug effects , Synaptic Transmission/physiologyABSTRACT
OBJECTIVE: Adenosine is an endogenous modulator of synaptic functions in the central nervous system. The effects of adenosine are mediated by at least four adenosine receptor subtypes. Decreased density of adenosine A1 receptors, which is a major subtype adenosine receptor in the hippocampus, has been reported in vitro in Alzheimer's disease. We evaluated adenosine A1 receptor in the brain of elderly normal subjects and patients with Alzheimer's disease (n = 8 and 6, respectively), using positron emission tomography (PET) and 8- dicyclopropylmethyl-1-[(11)C]methyl-3-propylxanthine ([(11)C]MPDX). METHODS: A 60-min PET scan with [(11)C]MPDX was performed. The patients with Alzheimer's disease also underwent PET with [(18)F]fluorodeoxyglucose (FDG). The binding potential of [11C]MPDX was quantitatively calculated in the regions of interest (ROIs) placed on the frontal, medial frontal, temporal, medial temporal, parietal, and occipital cortices, striatum, thalamus, cerebellum, and pons. Statistical parametric mapping (SPM2) was used for analysis of [(11)C]MPDX and FDG-PET. RESULTS: In the ROI-based analysis, the binding potential of [(11)C]MPDX in patients with Alzheimer's disease was significantly lower in the temporal and medial temporal cortices and thalamus than that in elderly normal subjects (P = 0.038, 0.028, and 0.039, respectively). SPM analysis also showed significant decreased binding potential in the temporal and medial temporal cortices and thalamus in patients with Alzheimer's disease. FDG uptake was significantly decreased in the temporoparietal cortex and posterior cingulate gyrus. CONCLUSIONS: Decreased binding of [(11)C]MPDX in patients with Alzheimer's disease was detected in temporal and medial temporal cortices and thalamus. This pattern possibly differed from the hypometabolism pattern of FDG. [(11)C]MPDX PET is valuable for the detection of degeneration in the temporal and medial temporal cortices and corticothalamic transmission, and may provide a different diagnostic tool from FDG-PET in brain disorders such as Alzheimer's disease.
Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Brain/diagnostic imaging , Brain/metabolism , Positron-Emission Tomography/methods , Receptor, Adenosine A1/metabolism , Xanthines/pharmacokinetics , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Tissue DistributionABSTRACT
Cardiac iodine-123-labeled-metaiodobenzylguanidine uptake is reduced in early-stage Parkinson's disease, suggesting sympathetic nerve degeneration. The scintigraphic findings in patients with Parkinson's disease with different clinical features have, however, not been established. Iodine-123-labeled-metaiodobenzylguanidine myocardial scintigraphy was performed in 143 patients with Parkinson's disease. The early and delayed heart to mediastinum ratios were analyzed according to the dominant motor deficit (tremor, bradykinesia, rigidity, and postural instability), age, sex, age at onset, disease duration, and Hoehn and Yahr stage. Both ratios correlated with bradykinesia, age at disease onset, and disease duration; but not with sex, Hoehn and Yahr stage, tremor, rigidity, and postural instability. Our results suggest a close link between myocardial sympathetic degeneration and bradykinesia, age at onset and disease duration.