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11.
David Mischoulon Darin D. Dougherty Kathryn A. Bottonari Robert L. Gresham Shamsah B. Sonawalla Alan J. Fischman Maurizio Fava 《Psychiatry Research: Neuroimaging》2002,116(3):151-161
Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [18F]-setoperone for 5-HT2 binding potential (BP) and [11C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [18F]-setoperone and with [11C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP. 相似文献
12.
Véronique Strijckmans Michel Bottlaender Humin Luo Michèle Ottavianil Daniel W. McPherson Christian Loc'h Chantal Fuseau Furn F. Knapp Bernard Mazière 《European journal of nuclear medicine and molecular imaging》1997,24(5):475-482
We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[76Br]BrQNP,E(-,-)-[76Br]BrQNP andE(-,+)-[76Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [76Br]BrNH4 and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M2 selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M1 selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., theE(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively.Z(-,-)-[76Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for theE(-,+)-[76Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors.Z(-,-)-[76Br]BrQNP, which is displaced in higher amounts from M2 mAChR-enriched structures, reveals an M2 affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and thecis-trans isomerism of the vinyl moiety affects their specific fixation. 相似文献
13.
P. Cumming T. K. Venkatachalam S. Rajagopal M. Diksic A. Gjedde 《Synapse (New York, N.Y.)》1994,17(2):125-128
The blood-brain permeabilities of L-[3H]tyrosine and the tyrosine hydroxylase (TH) inhibitor β-[14C]methyl-para-tyrosine ([14C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K1) for L-[3H]tyrosine (6.2 ml hg- ?1 min?1) was significantly greater than the rates for L-[14C]AMPT (2.8 ml hg?1 min?1) and D-[14C]AMPT (0.8 ml hg?1 min?1). The apparent volume of distribution (Vf) for L-[14C]AMPT in striatum (72.5 ± 4.0 ml hg-1) did not differ from the Vf in other brain regions. The homogeneous distribution of L-[14C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography. © 1994 Wiley-Liss, Inc. 相似文献
14.
Anders Persson Stefan Pauli Christer Halldin Sharon Stone-Elander Lars Farde Irene Sjgren Gran Sedvall 《Human psychopharmacology》1989,4(1):21-31
The 11C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced 11C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (Bmax) and equilibrium dissociation constant (Kd) values on the basis of certain assumptions Bmax values were in the order of 90 pmol/g and Kd values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that 11C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors. 相似文献
15.
Masafumi Ogawa Yasuhiro Magata Yasuomi Ouchi Hidenao Fukuyama Hiroshi Yamauchi Jun Kimura Yoshiharu Yonekura Junji Konishi 《Brain research》1994,650(2):249-252
The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H215O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated1.02 ± 0.02: 1.17 ± 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation. 相似文献
16.
正电子发射型断层显像在结直肠癌肝转移诊断中的应用 总被引:5,自引:0,他引:5
目的 评价正电子发射型断层显像(PET)在结直肠癌术后肝转移诊断中的作用。方法 对18例怀疑结直肠癌术后肝转移的患者和3例怀疑其他疾病的患者进行PET检查,通过与CT比较及手术探查,评价PET在结直肠癌肝转移诊断中的作用。结果 怀疑术后肝转移的18例患者,经PET显像确诊17例,其中14例同时伴有肝脏以外的其他脏器转移(肺转移2例、腹壁转移2例、骨转移1例、腹腔淋巴结转移6例、纵隔淋巴结转移2例、锁骨上淋巴结转移1例);PET诊断阴性的1例患者,随访1年后仍无瘤存活。3例怀疑其他疾病的患者经PET检查发现有结肠癌伴肝转移。结论 与CT相比,PET对结直肠癌术后肝脏及其他部位转移的敏感度更高,对术后肝转移患者是否选择再次手术具有更好的指导意义。 相似文献
17.
Håkan Eriksson Joakim Tedroff Karl-Åke Thuomas Sten-Magnus Aquilonius Per Hartvig Karl-Johan Fasth Peter Bjurling Bengt Långström Karl-Göran Hedström Edith Heilbronn 《Archives of toxicology》1992,66(6):403-407
A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-l-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-l-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-l-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i. e. before a reversal of the manganese accumulation. 相似文献
18.
Monique M. Cherrier Gary W. Small Scott Komo Asenath La Rue 《Psychiatry Research: Neuroimaging》1997,76(2-3):67-74
People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4±9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints. 相似文献
19.
Christian Foged Christer Halldin Christian Loc’h Bernard Mazière Stefan Pauli Mariannick Maziére Holger C. Hansen Tetsuya Suhara Carl-Gunnar Swahn Per Karlsson Lars Farde 《European journal of nuclear medicine and molecular imaging》1997,24(10):1261-1267
NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand
for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241.
This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised
by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake
of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after
injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with
flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection.
The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands
for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.
Received 19 April and in revised form 10 June 1997 相似文献
20.
利用PET—CT研究冠状动脉硬化性心脏病(Coronary artcry disease CAD)目前罕见报道:.单纯利用正电子发射断层显像(Positron emission tomography PET)对CAD的研究在国外已经取得了一定的进展。取得了一些经验,国内只有零星的报道;尚未开展比较系统的、规模的、符合我国实际特点的研究。多层螺旋CT(Muti-slices spiral computed 相似文献