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Biomedical subjects

K Shiba

Publications and source records attributed to K Shiba.

At least 163 records · Page 9Linked to original sources
PubMed1990

[Fundamental study on nuclear medicine imaging of cholinergic innervation in the brain: changes of neurotransmitter and receptor in animal model of Alzheimer's disease].

A fundamental study was performed on the nuclear medicine imaging of cholinergic innervation in the brain. In a cholinergic denervation model prepared by producing an unilateral basal forebrain lesion in the rat, which is reported to be one of animal models of Alzheimer's disease, quantitative determination of acetylcholine in parietal cortices revealed statistically significant 31% decrease on an average in the ipsilateral side relative to the contralateral side to the lesion. In vitro receptor autoradiography showed no significant differences in total, M1 and M2 muscarinic acetylcholine receptors between the ipsilateral and contralateral cortices to the lesion. Simultaneous mapping of presynaptic cholinergic innervation using 3H-2-(4-phenylpiperidino) cyclohexanol (AH5183) demonstrated significant 14% decrease of AH5183 binding on an average in the ipsilateral relative to the contralateral fronto-parieto-temporal cortices to the lesion. These results suggest that AH5183 is a promising ligand for mapping cholinergic innervation in nuclear medicine imaging.

Acetylcholine↗
PubMed1990

Autoradiographic analysis of iodoamphetamine redistribution in experimental brain ischemia.

The pathophysiologic significance of iodoamphetamine (IMP) redistribution was analyzed using a double radionuclide autoradiography technique in experimental brain ischemia in the rat. Within 4 hr after unilateral arterial occlusion, IMP almost completely redistributed at 150 min postinjection in the affected areas. At 2 min postinjection, both a remarkable decrease of IMP accumulation and histopathologic change of diminished staining were observed in these areas. The redistribution amplitude was higher in the affected hemisphere, especially in the regions surrounding the ischemic core than in the unaffected hemisphere. These findings were consistent with computer simulation studies of the time course of brain activity based on the standard diffusible tracer model. The results suggest that IMP redistribution in the ischemic area is due to differences of the temporal changes of the brain activity between the unaffected and affected areas and that it is a "physical" phenomenon (only flow related) rather than a "biologic" one.

Amphetamines↗
PubMed1989

Analogues of alpha-aminoisobutyric acid with various alkyl groups as potential tumour imaging agents; effects of chain length on tumour and normal tissue specificity.

Eight 14C-labelled analogues of alpha-aminoisobutyric acid (AIB) were synthesized using the modified Bucherer technique to investigate their tissue distribution in Ehrlich tumour bearing mice. A structure-activity relationship within a series of AIB analogues was found; increasing the chain length of R and R' produced a progressive decrease in tumour and a dramatic decrease in normal tissue uptake. AIB and alpha-amino-2-methyl-butanoic acid (AMB) were found to have higher tumour uptake than the other six analogues; and AMB and alpha-amino-2-ethyl-butanoic acid (AEB) showed higher tumour to tissue uptake ratios than the other six analogues, significantly so for liver, stomach, heart, and small intestine. These results indicate that AMB may be a potential tumour seeking agent for emission computed tomography.

Aminobutyrates↗
PubMed1989

[Pharmacokinetic evaluation of fluconazole in healthy volunteers].

Fluconazole, a novel triazole antifungal agent, was studied for its safety and pharmacokinetics following single oral or intravenous dose to 8 healthy male volunteers. Dosages employed were 25 mg, 50 mg and 100 mg orally and 25 mg and 50 mg intravenously. With oral doses, peak plasma levels were achieved in 2 hours in all subjects, with maximum plasma levels of 0.53 microgram/ml at a dose of 25 mg, 0.92 microgram/ml at 50 mg and 1.88 micrograms/ml at 100 mg showing a clear dose-response. Plasma-half lives of the drug were about 31 hours in both oral and intravenous administrations. Its urinary recoveries were about 70% as given orally as well as intravenously. There was no difference between areas under plasma concentration-time curves (AUC) obtained with the 2 administration methods. No side effects nor abnormal clinical test values were reported with any subjects studied.

Administration, Oral↗
PubMed1989

Double tracer autoradiographic method for sequential evaluation of regional cerebral perfusion.

A new double tracer autoradiographic method for the sequential evaluation of altered regional cerebral perfusion in the same animal is presented. This method is based on the sequential injection of two tracers, 99mTc-hexamethylpropyleneamine oxime and N-isopropyl-(125I)p-iodoamphetamine. This method is validated in the assessment of brovincamine effects on regional cerebral perfusion in an experimental model of chronic brain ischemia in the rat. The drug enhanced perfusion recovery in low-flow areas, selectively in surrounding areas of infarction. The results suggest that this technique is of potential use in the study of neuropharmacological effects applied during the experiment.

Amphetamines↗
PubMed1988

Quantitative assessment of cerebral blood flow using technetium-99m-hexamethyl-propyleneamine oxime: Part I, Design of a mathematical model.

To design a mathematical model for quantifying cerebral blood flow using 99mTc-hexamethyl-propyleneamine oxime (HM-PAO), basic studies were performed in animals and human volunteers. Microautoradiography revealed that HM-PAO crossed the blood-brain barrier. Thin layer chromatographic studies demonstrated the rapid disappearance of free HM-PAO in the brain tissue. Back diffusion from brain to blood was found negligible. From these observations, the familiar microsphere model was employed in the measurements of blood flow with HM-PAO. This, however, resulted in much lower flow values than simultaneously obtained values with the labeled microspheres. This underestimation was ascribed to the high affinity of HM-PAO to blood cells and serum protein. Taking the binding of HM-PAO to blood components into consideration, the following model equation was designed for quantifying cerebral blood flow: Ce(t) = Ca(t)-kCa(t)*exp(-kt), Cb(T) = F integral of T0 Ce(t)dt, where Ce and Ca are the free HM-PAO concentration in the intravascular space and the arterial whole-blood concentration of HM-PAO, respectively, as a function of time (t), Cb is the brain activity concentration, k is the rate constant for the binding of HM-PAO to the blood components, F is the blood flow value, T is time of measurement, and * denotes the operation of convolution. In clinical studies, Ca(t) and Cb(T) are obtainable from a dynamic single photon emission computerized tomographic study of the brain and multiple arterial blood sampling, respectively. The values for F and k can be estimated using a nonlinear least squares fitting method.

Animals↗
PubMed1988

Determination of flow and rate constants in a kinetic model of [99mTc]-hexamethyl-propylene amine oxime in the human brain.

The values for flow and rate constants for a kinetic model of [99mTc]-hexamethylpropyleneamine oxime (HM-PAO) distribution in the human brain were determined. The single-pass extraction ratio of HM-PAO was also determined in the rat brain by the indicator diffusion method; a value of 0.90 +/- 0.02 (mean +/- SEM, n = 5) was obtained. Time course data of brain activity and arterial blood activity of the tracer were fitted to a four compartment model: Values of blood flow and the first-order rate constants for backdiffusion of the diffusible tracer from brain to blood (k2), conversion of the lipophilic tracer to the hydrophilic one in brain (k3), and conversion of the diffusible tracer to the nondiffusible one in blood (k5) were determined. Conversion of hydrophilic tracer back to a lipophilic form in both blood and brain was assumed to be negligible during the course of the experiment. The values obtained for blood flow, k2, and k3 were, respectively, 0.40 +/- 0.03 ml/g/min, 0.38 +/- 0.04 min-1, and 0.92 +/- 0.05 min-1 in the gray matter (n = 4), and 0.23 +/- 0.01 ml/g/min, 0.17 +/- 0.01 min-1, and 1.01 +/- 0.05 min-1 in the white matter (n = 2) in patients with cerebrovascular disorder. The k5 value was 1.14 +/- 0.06 min-1 (n = 4). These experimentally determined values agree well with the theoretical ones previously reported by Lassen et al. The results suggest the relative constancy of the k3 and k5 values and the more prominent initial backdiffusion of the lipophilic HM-PAO from brain to blood in high flow regions compared to low flow regions.

Animals↗
PubMed1988

Direct autoradiographic comparison of 99Tcm-HMPAO with 125I-IMP in experimental brain ischaemia.

Local cerebral blood flow (LCBF) images of HMPAO and IMP were directly compared in experimental brain ischaemia in the same rats using a double-tracer autoradiographic technique. Both images were identical in distribution throughout the whole flow areas. However, LCBF values were much lower in HMPAO than in IMP. The results suggest that HMPAO acts as a chemical microembolus in rat brain in both low and high flow areas; however, a quantitative flow measurement is difficult in an HMPAO study.

Amphetamines↗
PubMed1988

[Analogs of alicyclic alpha-amino acids--effect of ring size and side chain on tumor accumulation].

We studied the tumor-localizing characteristics of alicyclic alpha-amino acid analogs (a-j) without alpha-hydrogen, because of the selective affinity of synthetic nonmetabolizing amino acids such as 1-aminocyclopentanecarboxylic acid (ACPC) and alpha-aminoisobutyric acid alpha-AIB) to tumor tissues. Ten different alicyclic alpha-amino acids (a-j) were labeled with 14C using a modified Bücherer synthesis for amino acids. The tissue distributions and whole-body autoradiographic study of these 14C-labeled alicyclic alpha-amino acid analogs (a-j) were investigated in mice bearing Ehrlich tumor. These results showed that the tumor uptakes and tumor to tissue concentration ratios increased with decreasing ringsize in homologous series (8- through 4-membered ring systems) and alicyclic alpha-amino acid analogs containing 3- or 4-methyl group had the higher tumor to tissue concentration ratios. On the other hand, alicyclic alpha-amino acid analogs containing 2-methyl group and 4-phenyl group showed the lower tumor uptakes and the lower tumor to tissue concentration ratios. These results suggest that the small ringsize alicyclic alpha-amino acid analogs containing 3-methyl group such as 3-methyl-1-aminocyclopentanecarboxylic acid (3-MeACPC) may be effective for the early detection of tumors.

Amino Acids↗
PubMed1987

In vitro evaluation of radioiodinated butyrophenones as radiotracer for dopamine receptor study.

Radioiodinated butyrophenone compounds are attracting the interest of those working on dopamine receptor studies; structure-activity relationship study has revealed the ortho position of the p-fluorobutyrophenone moiety as a very plausible iodination site. Various synthesized butyrophenones iodinated at the ortho position of p-fluorobutyrophenone moiety, 2'-iodohaloperidol (2'-IHP), 2'-iodotrifluperidol (2'-ITP) and 2'-iodospiperone (2'-ISP) were tested for their abilities to inhibit 3H-spiperone (SP) binding for the dopamine (D-2) receptor, together with reference compounds (SP, haloperidol(HP) and 4-iodospiperone (4-ISP]. The order of binding affinity of the tested compounds was SP greater than 2'-ISP greater than HP greater than 4-ISP greater than 2'-IHP greater than 2'-ITP. Whereas, the serotonin (S-2) receptor binding affinity of SP and its iodinated analogues were in the order of SP much greater than 4-ISP greater than 2'-ISP. Furthermore, in the saturation binding study using the striatal membrane preparations, the 2'-ISP displayed a KD of 0.25 nM with maximum number of binding site Bmax of 210 fmol/mg protein. These data indicated the 2'-ISP as holding high affinity for dopamine receptors and a low affinity for serotonin receptors. Thus, the 125I-2'-ISP was a very potent radioligand for in vitro dopamine (D-2) receptor studies, and 123I-2'-ISP holds very promising characteristics as for in vivo dopamine receptor studies, as well.

Animals↗
PubMed1987

Radioiodinated 2'-iodospiperone: a new radioligand for in vivo dopamine receptor study.

In vivo dopamine receptor binding of the newly synthesized ligand, 125I-2'-iodospiperone (125I-2'-ISP), was studied in mouse brain. The highest accumulation was found in the striatum. Analysis of the striatal homogenate showed the 125I-2'-ISP to be metabolically stable. Furthermore, this striatal binding was saturable and displaced only by dopaminergic drugs. On the other hand, the accumulation in the cortex was as low as that of the cerebellum and uneffected by the administration of serotoninergic drugs and dopaminergic drugs; results assessed by macroautoradiographic studies. Thus, the newly synthesized 125I-2'-ISP presented high affinity for dopamine receptors in vivo and therefore, holds great potential for the in vivo dopamine receptor studies, provided 123I becomes readily available.

Animals↗