Biomedical subjects

Y S Ding

Publications and source records attributed to Y S Ding.

At least 73 records · Page 4Linked to original sources

PubMed1995

Long-lasting inhibition of in vivo cocaine binding to dopamine transporters by 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester: RTI-55 or beta CIT.

Cocaine analogs such as 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) with a higher affinity for the dopamine transporter (DAT) may be potentially useful in interfering with cocaine's actions in brain. This study evaluates the time course of the effects of RTI-55 on cocaine binding in baboon brain using PET and [11C]cocaine. [11C]Cocaine binding was measured prior to, and 90 minutes, 24 hours, 4-5 days and 11-13 days after RTI-55 (0.3 mg/kg i.v.). Parallel studies with [3H]cocaine and RTI-55 (0.5 mg/kg i.v. or 2 mg/kg i.p.) were performed in the mouse. RTI-55 significantly inhibited [11C]cocaine binding at 90 minutes and 24 hours after administration. The half-life for the clearance of RTI-55 from the DAT was estimated to be 2 to 3 days in the baboon brain. In the mouse brain, RTI-55 significantly inhibited [3H]cocaine binding at 60 and 180 minutes after administration and recovery was observed at 12 hours. These results document long-lasting inhibition of cocaine binding by RTI-55 and corroborate that binding kinetics of RTI-55 in striatum observed in imaging studies with [123I]RTI-55 represents binding to DATs.

Animals↗

PubMed1995

Comparison of two pet radioligands for imaging extrastriatal dopamine transporters in human brain.

We compared the sensitivity of two dopamine transporter (DAT) ligands ([C-11]cocaine and [C-11]d-threo-methylphenidate) for measurement of extrastriatal DAT availability using positron emission tomography (PET) on separated groups of 10 age matched male volunteers (age range, 21-49 years). DAT availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum (Bmax'/Kd'+ 1). DAT availability measured with [C-11]d-threo-methylphenidate was highest in basal ganglia, followed by thalamus > temporal insula, cingulate > orbitofrontal, frontal and occipital cortices. A similar ranking order for DAT availability was obtained with [C-11]cocaine. Specific binding (Bmax'/Kd') of [C-11]cocaine in thalamus was 25-33% that of basal ganglia and [C-11]d-threo-methylphenidate in thalamus was 11-13% that of basal ganglia. The regional measures with [C-11]cocaine were significantly correlated with those of [C-11]d-threo-methylphenidate (p < or = 0.0001). These results document extrastriatal binding in human brain with two different DAT ligands.

Adult↗

PubMed1995

Mechanistic positron emission tomography studies of 6-[18F]fluorodopamine in living baboon heart: selective imaging and control of radiotracer metabolism using the deuterium isotope effect.

Mechanistic positron emission tomography (PET) studies using the deuterium isotope effect and specific pharmacological intervention were undertaken to examine the behavior of 6-[18F]fluorodopamine (6-[18F]-FDA; 1) and (-)-6-[18F]fluoronorepinephrine [(-)-6-[18F]FNE; 2] in the baboon heart. Two regiospecifically deuterated derivatives of 6-[18F]FDA [alpha,alpha-D2 (3) and beta,beta-D2 (4)] were used to assess the contributions of monoamine oxidase (MAO) and dopamine beta-hydroxylase, respectively, to the clearance kinetics of 6-[18F]FDA. Compound 3 showed a reduced rate of clearance, consistent with MAO-catalyzed cleavage of the alpha C-D bond, whereas compound 4 showed no change, indicating that cleavage of the beta C-D bond is not a rate-limiting step. Pretreatment with pargyline, an MAO inhibitor, also decreased the rate of clearance. Desipramine and tomoxetine [norepinephrine (NE) uptake inhibitors], but not GBR-12909 (a dopamine uptake inhibitor), blocked the uptake of both (-)-6-[18F]FNE and 6-[18F]FDA, with (-)-6-[18F]FNE showing a higher degree of blockade. Chiral HPLC demonstrated that 6-[18F]FDA is stereoselectively converted to (-)-6-[18F]FNE in vivo in the rat heart. These studies demonstrate that (a) the more rapid clearance of 6-[18F]FDA relative to (-)-6-[18F]FNE can be largely accounted for by metabolism by MAO; (b) selective deuterium substitution can be used to protect a radiotracer from metabolism in vivo and to favor a particular pathway; (c) 6-[18F]FDA and (-)-6-[18F]FNE share the NE transporter; (d) 6-[18F]FDA is stereoselectively converted to (-)-6-[18F]FNE in vivo; and (e) the profile of radioactivity in the heart for 6-[18F]FDA is complex, probably including labeled metabolites as well as neuronal and nonneuronal uptake.

Animals↗

PubMed1995

[Localization value of intra-esophageal atrial pacing by modified digitus medius proportional unit].

The length of lead electrode which was eleven times the length of modified digitus medius proportional unit used for intra-esophageal atrial pacing on 86 patients was compared with the length lcm more or less than the lead length itself showed very significant difference in pacing threshold, which was low, adverse reaction was mild, the intra-esophageal P wave display was satisfactory. It could alleviate the patient's pain, and was easy to manipulate, practical, rapid and inexpensive in diagnosis and treatment of arrhythmia, rescuing indoor or outdoor emergency cases as well as monitoring operation.

Anthropometry↗

PubMed1995

Serotonergic modulation of striatal dopamine measured with positron emission tomography (PET) and in vivo microdialysis.

Positron emission tomography and in vivo microdialysis were used to study serotonin's role in modulating striatal dopamine. Serial PET studies were performed in adult female baboons at baseline and following drug treatment, using the dopamine (D2) selective radiotracer, 11C-raclopride. The serotonergic system was manipulated by administration of the selective 5-HT reuptake inhibitor, citalopram, or by serotonergic (5-HT2) receptor blockade (using altanserin, a 5-HT2 antagonist). 11C-Raclopride time-activity data from striatum and cerebellum were combined with plasma arterial input functions and analyzed by calculating a distribution volume as described previously (Logan et al., 1990). Additionally, in vivo microdialysis studies were performed in awake freely moving rats using similar pharmacologic challenges plus SR 46349B, a new highly selective 5-HT2 receptor antagonist. Altanserin and SR 46349B increased extracellular striatal dopamine concentrations (35% and 910%, respectively) while altanserin decreased striatal 11C-raclopride binding (37%). Citalopram, however, decreased extracellular striatal dopamine concentrations (50%) and increased 11C-raclopride binding (33%). These data demonstrate that 5-HT-selective drugs produce changes in striatal dopamine that can be measured noninvasively with PET. Furthermore, the PET data obtained from anesthetized baboons is consistent with in vivo microdialysis data obtained from awake and freely moving rats. Finally, these studies have implications for understanding the therapeutic efficacy of atypical neuroleptics and their utility for treating schizophrenia and affective disorders.

Animals↗

PubMed1995

A new PET ligand for the dopamine transporter: studies in the human brain.

UNLABELLED: Carbon-11-d-threo-methylphenidate, the active enantiomer of methylphenidate (ritalin), has been shown to bind uniquely to the dopamine transporter in the baboon brain. This study characterizes its binding in the human brain and measures its test-retest reproducibility. METHODS: Studies were done in seven normal controls, each of whom was scanned with [11C]d-threomethylphenidate on two different occasions. Six subjects were scanned twice 3-5 wk apart without intervention to assess reproducibility. One subject was scanned sequentially before and after treatment with methylphenidate to assess binding saturability. Graphical analysis was used to obtain tissue distribution volumes (DV). The ratio of the DV in the basal ganglia (BG) to that in cerebellum (CB) (DVBG/DVCB), which corresponds to (Bmax/Kd) + 1 was used to estimate dopamine transporter availability. RESULTS: Highest tracer uptake occurred in the basal ganglia, where activity peaked 7-11 min postinjection. The half-clearance time for the tracer in brain regions other than the basal ganglia was 74 min. In the basal ganglia, only 10%-15% of the activity had cleared at 74 min. Time-activity curves for [11C]d-threo-methylphenidate in the basal ganglia and cerebellum were highly reproducible. The average percent change for the absolute value for DVBG/DVCB was 6.5% +/- 4% (range 0-12%). Methylphenidate pretreatment decreased basal ganglia uptake but not cortical or cerebellar binding and reduced DVBG/DVCB by 62% and Bmax/Kd by 91%. CONCLUSION: These studies demonstrate that [11C]d-threo-methylphenidate binding in the human brain is reversible, highly reproducible and saturable. Thus, it is an appropriate PET ligand to measure dopamine transporter availability.

Adult↗

PubMed1995

Carbon-11-d-threo-methylphenidate binding to dopamine transporter in baboon brain.

UNLABELLED: The more active d-enantiomer of methylphenidate (dl-threo-methyl-2-phenyl-2-(2-piperidyl)acetate, Ritalin) was labeled with 11C(t1/2:20.4 min) to characterize its binding, examine its specificity for the dopamine transporter and evaluate it as a radio-tracer for the presynaptic dopaminergic neuron. METHODS: PET studies were carried out in the baboon. The pharmacokinetics of [11C]dl-threo-methylphenidate, [11C]l-threo-MP and with its racemate ([11C]dl-threo-methylphenidate, [11C]MP). Nonradioactive methylphenidate was used to assess the reversibility and saturability of the binding. GBR 12909, 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester (beta-CIT), tomoxetine and citalopram were used to assess the binding specificity. RESULTS: The ratio between radioactivity in the striatum and that in the cerebellum (ST/CB) after injection of [11C]d-threo-MP was higher than that for [11C]MP and [11C]l-threo-MP (3.3 for d-, 2.2 for racemic and 1.1 for l- in the same baboon). Most of the striatal binding of [11C]d-threo-MP was displaceable by injection of nonradioactive MP. Pretreatment with nonradioactive MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) and RTI-55 (0.3 mg/kg) markedly reduced striatal but not cerebellar uptake of [11C]d-threo-MP. In all cases, the ST/CB after pretreatment was reduced by about 60% compared to 43% for [11C]MP. The ratios of distribution volumes at steady-state for the ST/CB for the three separate studies in the same baboon were reduced by about 50%, as compared with 37% for [11C]MP. In contrast, pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg) did not change [11C]d-threo-MP kinetics; the ST/CB after pretreatment was similar to that for the control. CONCLUSION: These results demonstrate the saturable, reversible and specific binding of [11C]d-threo-MP to the dopamine transporter on the baboon brain, suggesting that [11C]d-threo-MP will be a useful PET tracer for the presynaptic dopaminergic neuron in living human brain.

Animals↗

PubMed1994

Binding of bromine-substituted analogs of methylphenidate to monoamine transporters.

We synthesized the o-, m- and p-bromo derivatives of dl-threo-methylphenidate from the corresponding bromophenylacetonitriles by modification of the literature synthesis of methylphenidate (Panizzon, Helv. Chim. Acta 1944, 27, 1748). In in vitro binding assays all three dl-threo bromo compounds had higher affinities than methylphenidate for dopamine transporter sites labeled with [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428; IC50 = 13, 4, 20 and 82 nM for o-, m-, and p-bromo compounds, and unsubstituted methylphenidate, respectively). They also bound more strongly than methylphenidate to norepinephrine reuptake sites labeled with [3H]nisoxetine (IC50 = 32, 20, 31 and 440 nM, respectively), but were weak ligands (IC50 > or = 1 microM) at the serotonin transporter labeled with [3H]paroxetine. In addition, the bromine substituted derivatives demonstrated similar activity to methylphenidate in vivo in rodents in terms of inhibition of heart uptake of [3H](-)-norepinephrine, elevation of striatal extracellular dopamine, and stimulation of locomotor activity.

Animals↗

PubMed1994

PET studies of cocaine inhibition of myocardial norepinephrine uptake.

Positron emission tomography (PET), [11C]cocaine, and (-)-6-[18F]fluoronorepinephrine [(-)-6-[18F]NE] were used to determine the extent to which the binding of labeled cocaine in the baboon heart represents binding to the norepinephrine transporter and to characterize the functional consequences of cocaine administration on the norepinephrine transporter. Peak heart binding of [11C]cocaine was high (0.038-0.055%/g) and clearance was rapid (t1/2 from peak: 2.5-9 min) for both tracer doses and a pharmacological dose. The binding of a tracer dose of labeled cocaine could not be inhibited by desipramine, tomoxetine, cocaine, nomifensine, or benztropine. The behavior of a pharmacological dose of [11C]cocaine could not be distinguished from a tracer dose and also could not be inhibited by tomoxetine. However, pretreatment with cocaine profoundly inhibited norepinephrine uptake as assessed by (-)-6-[18F]NE. Recovery was slow with only 48% of the baseline (-)-6-[18F]NE uptake being recovered by 78 minutes after cocaine administration. [11C]Benzoylecgonine, a vasoactive metabolite of cocaine, showed negligible retention in heart. The results of this study (i.e., the rapid clearance of cocaine from the heart, the inability to inhibit cocaine binding with desipramine and tomoxetine, and its relatively long-lasting effects on norepinephrine uptake) reinforce the need to understand the link between cocaine pharmacokinetics and norepinephrine transporter function and its relationship to cardiotoxicity.

Animals↗

PubMed1994

Pharmacokinetics and in vivo specificity of [11C]dl-threo-methylphenidate for the presynaptic dopaminergic neuron.

dl-threo-Methylphenidate (Ritalin) was labeled with carbon-11 (t1/2:20.4 minutes) in order to measure its pharmacokinetics, to evaluate it as a radiotracer for the presynaptic dopaminergic neuron, and to examine its sensitivity to the loss of dopaminergic neurons. Positron emission tomographic (PET) studies were carried out in the baboon to determine specificity for the presynaptic dopaminergic neuron and in humans to assess sensitivity to neuronal loss. Studies with [11C]dl-threo-methylphenidate ([11C]MP) in baboon demonstrated high regional uptake in the striatum. Peak uptake (0.04%/cc) occurred at 5-15 minutes post-injection. The half-time for clearance from peak uptake for [11C]MP was 60 minutes and the ratio between the radioactivity in the striatum and that in the cerebellum (ST/CB) ranged from 2.2 to 2.6 at 40 minutes. Repeated measures in the same baboon showed < or = 8% variability in the ST/CB ratio. Pretreatment with unlabeled methylphenidate (0.5 mg/kg) or GBR12909 (1.5 mg/kg) 30 minutes prior to [11C]MP injection markedly reduced the striatal but not the cerebellar uptake of [11C]MP, demonstrating the saturable and specific binding of [11C]MP to a site on the dopamine transporter in the brain. In both cases, the ratio of striatum to cerebellum (ST/CB) after pretreatment was reduced by about 43%. The ratios of distribution volumes at the steady-state for the striatum to cerebellum (ST/CB) for these two separate studies in the same baboon were reduced by 37 and 38%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Biomaterials with permanent hydrophilic surfaces and low protein adsorption properties.

Low protein adsorbing polymer films have been prepared with which to fabricate intravenous containers, designed for compatibility with low concentrations of protein drugs. The material is economically manufactured utilizing physical melt blending of water-soluble surface-modifying polymers (PEO, PEOX, PVA, and PNVP) with a base polymer (EVA, PP, PETG, PMMA, SB, and nylon). Permanency of the hydrophilic surfaces so generated was confirmed by surface contact angle experiments and total organic carbon leachables analysis of the aqueous contacting solutions. Binding of IgG, albumin and insulin was studied. A sixfold reduction of protein adsorption was obtained by adding 5% PVA13K to EVA, for IgG at a bulk concentration of 2.5 ppm. Surface bound protein measured by micro-BCA colorimetry, agreed with the solution protein lost, as determined by the Fluoraldehyde procedure. Imaging of the protein exposed plastic surfaces by silver enhanced protein conjugated gold staining agreed with the quantitative assay determinations.

Adsorption↗

PubMed1994

[Experimental study on the processed drug of castor seeds in the therapy of pulmonary carcinoma].

In this study, castor seeds were processed by one of the traditional Chinese methods, LD50 was measured and tumor inhition tests in nude mice bearing human pulmonary carcinoma were conducted. The results showed that the processing method was able to lower the toxicity of castor seeds and maintain their antitumor effect, thus providing an experimental basis for oral administration of castor seeds in the therapy of pulmonary carcinoma.

Adenocarcinoma↗

PubMed1994

A report on selective radiofrequency ablation of dual atrioventricular node pathways in 34 cases.

Selective ablation of slow pathway by radiofrequency (RF) current in 34 patients with atrioventricular (AV) node pathways and tachycardia was performed with two methods in our section; posterior approach was used in the first 12 patients, the slow pathways were ablated successfully. Inferior approach was performed in the other 22 patients. Slow pathways were interrupted in 14 patients. Retrograde fast pathways and/or slow pathways were ablated in 6 patients. Retrograde fast pathways and slow pathways were abolished and antegrade fast pathways were injured transitorily in 2 cases. The total procedure time was shorter, RF applications were fewer by inferior approach than by posterior approach (P < 0.05). Both antegrade and retrograde conduction of fast pathways had not been affected after slow pathways were ablated (P > 0.05). After a mean of 8 months follow-up, two patients recurred and were ablated successfully again. We come to the conclusion that inferior approach might be a preferable method compared with posterior approach; the slow pathways is the compact node and its posterior input of transitional cells; the retrograde fast pathway may be the anterior superficial group of transitional cells and is not always in the same location of antegrade fast pathway.

Adult↗

PubMed1994

Endocardial mapping and radiofrequency catheter ablation of multiple atrioventricular accessory pathways.

UNLABELLED: Among 174 patients with Wolff-Parkinson-White syndrome, 13 (17.5%) had multiple atrioventricular (AV) accessory pathway. Twenty-one of the 29 pathways were identified by baseline electrophysiologic study and eight were found after the radiofrequency ablation of the initial ones. Bilateral ablation approach was tried in four patients and unilateral approach in nine. Twenty-seven of the pathways (93.1%) were eliminated permanently after a mean of 32 +/- 14 pulses of current delivery. There were no complications. The pulses was more and the procedure took more time (3.6 +/- 0.8 hr) in the group compared to those in single pathway ablation (14 +/- 11 and 2.1 +/- 0.8 hr respectively, P < 0.05). The success rate was identical in the two patient populations (93.1% vs 94.0%, P > 0.05). However, the recurrence in multiple pathway ablation (7.6%) was more than that in single pathway ablation (1.9%, P < 0.01). CONCLUSION: radiofrequency catheter ablation is a safe and effective modality for tachyarrhythmias mediated by multiple accessory pathways.

Adult↗

PubMed1993

Synthesis and PET studies of fluorine-18-BMY 14802: a potential antipsychotic drug.

BMY 14802 is a compound containing fluorine developed as a potential antipsychotic drug. It has a moderate affinity for the sigma binding site and a very low affinity for dopamine D2 receptors and has been predicted to have antipsychotic properties without the side effect potential of existing drugs. To assess the brain uptake, pharmacokinetics, stereoselectivity and binding properties of this potential antipsychotic drug, enantiomerically pure samples of (-) and (+)-[18F]BMY 14802 were examined in a baboon with PET. A tissue distribution with racemic labeled BMY 14802 was also carried out in mice. Radiochemical yields of 15% at the end of bombardment (EOB) for the racemic mixture, and 5% for each enantiomer with a specific activity of 2-5 Ci/mumol at EOB were obtained. In baboons, [18F]BMY 14802 cleared rapidly from the plasma and the glucuronidated [18F]BMY 14802 appeared. Radioactivity peaked (0.04-0.07% dose/cc) in all areas of the brain examined at about 5 min postinjection. It then rapidly cleared to about 30% of peak value by 20 min postinjection and to less than 10% of peak by 60 min postinjection in all regions. A similar rapid clearance from brain was also observed in mice. Pretreatment with unlabeled BMY 14802 (7 mg/kg), did not produce the expected reductions in distribution volume and clearance halftimes consistent with receptor binding. Although the rapid kinetics of [18F]BMY 14802 made it difficult to resolve the processes of transport and binding of the labeled drug, the lack of regional distribution consistent with the known distribution of sigma binding sites as well as the lack of stereoselectivity suggest that the behavior of BMY 14802 in the brain is dominated by its transport properties in tissue rather than its binding to sigma sites. Moreover, its rapid clearance from brain may be a limiting factor in its use as an antipsychotic drug.

Animals↗

PubMed1993

[Catheter radiofrequency current ablation of septal atrioventricular accessory pathway in patients with Wolff-Parkinson-White syndrome].

Thirteen patients with Wolff-Parkinson-White syndrome were ablated with radiofrequency current. The thirteen septal atrioventricular accessory pathways in these patients included 4 right anteroseptal, 4 right posteroseptal and 5 left posteroseptal. For patients with right anteroseptal and posteroseptal accessory pathways, a large-tip ablation catheter was advanced via right femoral vein to an area just above the His bundle and around the coronary sinus ostium. For patients with left posteroseptal accessory pathways. An ablation catheter was placed at the left ventricular side of mitral annulus. All of the accessory pathways were abolished successfully. The average current applications was 14 and mean accumulated energy was 18,900 joules. The mean procedure period is 2.3 hours. There were no severe complications and there was no recurrence after 6 months of follow-up. It is shown that radiofrequency current ablation of septal accessory pathways in patients with Wolff-Parkinson-White syndrome is a safe and effective modality of treatment.

Adolescent↗

PubMed1993

Radiofrequency current ablation of atrioventricular accessory pathway.

Catheter ablation of atrioventricular accessory pathway by radiofrequency current is a new treatment for patients with refractory supraventricular tachycardia. 71 patients (37 male, 34 female, mean age 36 +/- 11 years) with 77 atrioventricular accessory pathways were ablated in the study. Left-sided pathways were ablated at the ventricular side of mitral annulus by using large-tip ablation catheter. While right-sided pathways were ablated along the tricuspid annulus, 70 (90.9%) accessory pathways of 64 patients (90.1%) were blocked successfully. There were no deaths. Left femoral vein thrombosis occurred in one patient. Recurrence was found in 3 patients (4.2%) after 7 months of follow-up and all of them were ablated again successfully.

Adult↗

PubMed1993

Comparison of high specific activity (-) and (+)-6-[18F]fluoronorepinephrine and 6-[18F]fluorodopamine in baboons: heart uptake, metabolism and the effect of desipramine.

(-)-Norepinephrine is the principal neurotransmitter of the mammalian sympathetic nervous system and a major CNS neurotransmitter. The simple ring fluorinated derivatives of (-)- and (+)-norepinephrine [(-)- and (+)6-fluoronorepinephrine] and dopamine (6-fluorodopamine) have been labeled with 18F in high specific activity (2-5 Ci/mumol) and evaluated as tracers for (-)-norepinephrine. Comparative PET studies of (-) and (+)-6-[18F]fluoronorepinephrine [(-)-6-[18F]FNE and (+)-6-[18F]FNE] and 6-[18F]fluorodopamine (6-[18F]FDA) in the same baboon showed strikingly different kinetics in the heart. Analysis of plasma showed more rapid metabolism of 6-[18F]FDA with only 1%-2% of 18F remaining as parent tracer at 10 min after injection of 6-[18F]FDA, in contrast to 28% and 17% remaining after injection of (-) and (+)-6-[18F]FNE. No changes in vital signs were observed at any time during the study. Pretreatment with desipramine (0.5 mg/kg), a tricyclic antidepressant drug which interacts with a binding site associated with norepinephrine reuptake, markedly decreased cardiac uptake of 6-[18F]FDA and (-)-6-[18F]FNE. However, a greater blocking effect was observed for (-)-6-[18F]FNE. These studies show that (-) and (+)-6-[18F]FNE are similar to (-)- and (+)-norepinephrine in their patterns of metabolism and clearance in the heart and that (-)-6-[18F]FNE is a promising tracer for endogenous (-)-norepinephrine.

Animals↗