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E K Shaya

Publications and source records attributed to E K Shaya.

7 recordsLinked to original sources

Cerebral glucose utilization is reduced in second test session.

Cerebral glucose utilization was higher during the first positron emission tomography (PET) session than during the second session, as assayed using the PET [18F]fluorodeoxyglucose method in male human volunteers. This difference was due largely to data from subjects with low-trait anxiety, since subjects with high anxiety showed similar metabolism in both PET sessions. High-anxiety subjects showed greater right/ left ratios of cerebral metabolism than low-anxiety subjects, particularly during the second PET session. These findings suggest that the level of anxiety may be an important variable to consider in PET studies using multiple sessions.

Adult↗

Cerebral glucose utilization in polysubstance abuse.

Regional cerebral glucose metabolism in subjects with histories of polysubstance abuse was compared to that in control subjects who were drawn from the same community. The substance abuse group showed lower absolute metabolic rates for glucose in lateral occipital gyrus and higher normalized metabolic rates in temporal and frontal areas, including orbitofrontal cortex. It is suggested that some patterns of brain function associated with polysubstance abuse may represent consequences of drug exposure, or they could reflect pre-existing differences that may be relevant to the etiology and maintenance of polysubstance abuse.

Adult↗

In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428.

[11C]WIN 35,428 was evaluated as a specific in vivo radioligand for the dopamine transporter site by PET scanning in nonhuman primates and humans. In studies with a baboon (Papio anubis), [11C]WIN 35,428 accumulated in brain regions containing dopamine transporters, i.e., the striata. This accumulation was partially blocked by prior administration of (-)cocaine (4 mg/kg, i.v.). Placement of a unilateral lesion of dopamine-containing nerve terminals with MPTP resulted in a unilateral reduction in [11C]WIN 35,428 accumulation in the striatum on the side of the lesion. Imaging of D2 dopamine receptors with [11C]NMSP in the same MPTP-treated animals showed much less reduction in the postsynaptic D2 dopamine receptors as compared to the much larger reduction in the dopamine transporters labeled with [11C]WIN 35,428. A total of ten normal human volunteers (five males and five females) with ages ranging from 19 to 81 years were studied. The caudate/cerebellar and putamen/cerebellar ratios ranged from 4.4 to 5.7 90 min after injection of the tracer. Preliminary kinetic modeling with arterial plasma sampling resulted in an average binding potential (k3/k4) of 4.98 in the caudate nucleus and 5.13 in putamen. To demonstrate in vivo blockade with dopamine reuptake inhibitors, two subjects received prior oral doses of 6 mg mazindol. Subject 5 had significant reductions of 29% in the caudate/cerebellar ratio at 90 min, 35% in the putamen/cerebellar ratio at 90 min, 45% in the caudate k3/k4 ratio from 6.7 to 3.7, and 46% in the putamen k3/k4 from 4.7 to 2.5. Subject 8 had significant reductions of 20% in both the caudate/cerebellar ratio and the putamen/cerebellar ratio at 90 min. During the human PET studies, a number of neuropsychological tests and physiological measurements were performed. No significant changes were found after administration of the [11C]WIN 35,428 alone. Taken together, these data indicate that [11C]WIN 35,428 is a promising radioligand for future studies of neuropsychiatric disorders that involve the dopamine transporter site.

Adult↗

Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone.

Positron emission tomography (PET) with 11C-N-methylspiperone as the radioligand was carried out in 25 chronic schizophrenic patients to determine dopamine D2 receptor density estimates in the corpus striatum. The sample included 18 neuroleptic-naive and 7 neuroleptic-free patients. Dopamine D2 receptor density estimates (Bmax) were obtained using a two-scan/four-compartment model. The Bmax estimates for the entire group (33.39 +/- 3.43 pmole/g) were significantly elevated when compared with estimates for the control group (Bmax = 15.63 +/- 2.38). The Bmax values for the entire group of schizophrenic patients showed a significant decline as a function of age. The Bmax values were significantly related to duration of illness (y = 13.2 + 10.3795x - 0.7931x2; r = 0.48). Thirteen patients and seven control subjects were added to our original publication sample (Wong et al., 1986c). The patients' Bmax values, when adjusted for age and sex effects, were significantly different compared with those of control subjects. Clinical data from the entire group were compared with published data from other research groups that have estimated dopamine D2 receptor density using different radioligands and different methods of data analysis. Comparisons of the clinical characteristics of the published studies show significant differences in patient populations, suggesting that discrepancies among published studies may reflect, in part, heterogeneity among groups of schizophrenic patients. The D2 receptor abnormality described in this study may be a late manifestation of disease, and the implications of this observation are discussed.

Adult↗

Sensitivity to subjective effects of cocaine in drug abusers: relationship to cerebral ventricle size.

OBJECTIVE: The purpose of this study was to assess the functional significance of ventricle-brain ratio (VBR) in terms of how it might affect sensitivity to cocaine, an indirect dopamine agonist. METHOD: Relationships between VBR and subjective responses to acute intravenous cocaine hydrochloride were examined in 20 male polydrug abusers. Tests were performed in conjunction with positron emission tomography scans to measure cerebral glucose metabolism. RESULTS: Subjective measures of effects of cocaine, including self-report ratings of intensity of the drug effect, scores on the morphine-benzedrine scale of the Addiction Research Center Inventory, and several items on visual analogue scales, correlated negatively with VBR. VBR also differed significantly among subjects who were grouped according to scores on items ("rush" and "crash") of the Cocaine-Sensitive Scale (larger VBR in subjects with weaker responses). VBR was not correlated with cocaine-induced changes in cerebral metabolic rates for glucose. CONCLUSIONS: Relative insensitivity to the subjective effects of cocaine in polydrug abusers with ventricle enlargement suggests that ventriculomegaly may reflect changes in periventricular brain regions that mediate these effects of cocaine.

Adult↗

Effects of vasopressin on blood-brain transfer of methionine in dogs.

We used a simplified probe detection system for positron-emitting radionuclides in order to measure blood-brain barrier transport of amino acids in anesthetized dogs. Plasma and brain time-activity curves were recorded after intravenous bolus injection of L-[11C]methionine before and after administration of 1 microgram of vasopressin. Three-compartment models with three or four transfer coefficients were used to derive the kinetics of L-[11C]methionine uptake in brain. The blood-brain clearance of the tracer (K1) was 0.075 ml ml-1 min-1 before and 0.041 ml ml-1 min-1 after injection of vasopressin. The partition volume and the initial distribution (plasma) volume of methionine were unchanged and within the expected limits. The net accumulation rate of methionine (K), estimated by both the four-parameter (kinetic) and three-parameter (graphic) approaches, decreased after vasopressin injection in all six studies.

Animals↗