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11.
Comparison of Three 18 F-Labeled Butyrophenone Neuroleptic Drugs in the Baboon Using Positron Emission Tomography 总被引:1,自引:0,他引:1
Carroll D. Arnett Chyng-Yann Shiue Alfred P. Wolf Joanna S. Fowler Jean Logan Masazumi Watanabe 《Journal of neurochemistry》1985,44(3):835-844
The butyrophenone neuroleptics spiroperidol, benperidol, and haloperidol were radiolabeled with fluorine-18 and studied in baboon brain using positron emission transaxial tomography (PETT). Pretreatment of the baboon with a high pharmacological dose of (+)-butaclamol reduced the specifically bound component of radioactivity distribution in the striatum to approximately the radioactivity distribution found in the cerebellum. Comparative studies of brain distribution kinetics over a 4-h period indicated that either [18F]spiroperidol or [18F]benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8-h study with [18F]spiroperidol, striatal radioactivity did not decline, suggesting that spiroperidol either has a very slow dissociation rate or that it binds irreversibly to these receptors in vivo. [18F]Haloperidol may not be suitable for in vivo PETT studies, because of a relatively high component of nonspecific distribution and a faster dissociation from the receptor. Analysis of 18F in plasma after injection of [18F]spiroperidol indicated rapid metabolism to polar and acidic metabolites, with only 40% of the total radioactivity being present as unchanged drug after 30 min. Analysis of the metabolic stability of the radioactively labeled compound in rat striatum indicated that greater than 95% of [18F]spiroperidol remains unchanged after 4 h. 相似文献
12.
Clinical factors influencing the absorption of 125I-NPH insulin in diabetic patients 总被引:1,自引:0,他引:1
Clinical factors which might influence the absorption of subcutaneously injected 125I-NPH insulin were studied in 101 diabetics. The disappearance curve was monoexponential after a delay period of 1.5 +/- 0.8 h (mean +/- SD). Lipohypertrophy significantly prolonged insulin absorption (half life (T1/2) = 11.2 +/- 3.1 h, p = 0.0001). Low bicarbonate levels increased the absorption (T1/2 3.9 +/- 2.3 h, p less than 0.05). Lean diabetics had a faster absorption (6.2 +/- 1.9 h) than normal weight diabetics (7.5 +/- 2.0 h, p less than 0.02). Sex, age, diabetes duration and injection depth did not influence T1/2. The half life was significantly inversely correlated to the resting subcutaneous blood flow (r = 0.882, p less than 0.01). The overall interindividual coefficient of variation for insulin absorption in nonketotic diabetics was 27.4%. Also considerable intra-patient day-to-day variation was found (24.5%), and between different injection sites (30.2%). These variations emphasize the drawbacks of conventional insulin therapy in the management of insulin-requiring diabetics. 相似文献
13.
Joanna Strosznajder Laurie Foudin Wilson Tang Grace Y. Sun 《Journal of neurochemistry》1983,40(1):84-90
Arachidonate incorporation into synaptosomal phospholipids was shown to be affected by factors including the procedure for preparation of the membrane fractions and preincubation of synaptosomes prior to assay of incorporation of arachidonate into both phosphatidylcholine (PC) and phosphatidylinositol (PI). However, the inhibition toward incorporation into PIs, but not PCs, was fully reversed when the membranes were washed with bovine serum albumin. A twofold increase in arachidonate incorporation into PIs was also observed when freshly prepared synaptosomes were washed with serum albumin immediately before assay of incorporation activity. The inhibitory action is thought to be due to an increase in polyunsaturated fatty acids and/or their oxidation products which may then elicit a special effect on the acyltransferase responsible for transferring arachidonate into phosphatidylinositols. The differences in fatty acid uptake and response to serum albumin also suggest the presence of different acyltransferase for acyl transfer to PIs and PCs. 相似文献
14.
Summary 1. On the seaward face of Port Erin breakwater large algae do not occur on the lowest three metres. Here the density ofEchinus esculentus is high.2. Over a three year period allEchinus were removed from a 10 m wide strip at about monthly intervals. The total number of individuals removed approached 3000.3. One year after initial clearance the mean density ofLaminaria hyperborea sporelings on the strip was 22.7/m2 and 5.1/m2 to one side of it. By the winter these had almost disappeared outside the strip and in the succeeding years second and third year plants were found only on the strip or close to its edge. Other algae were similarly affected.4. It is concluded that the lower limit ofL. hyperborea is determined at least in part by the grazing pressure ofEchinus and that the urchins exercise some control over the numbers of other algae.
Algenkolonisation im untergetauchten Gezeitenbereich nach Entfernung vonEchinus
Kurzfassung An der Sesseite des Port Erin Wellenbrecherdammes kommen keine größeren Algen im Bereich der unteren 3 m vor. Hier herrscht eine große Besiedlungsdichte des SeeigelsEchinus esculentus (3,6 Individuen pro m2). Über eine Zeitspanne von 3 Jahren wurden nun sämtlicheE. esculentus von einem 10 m breiten und 12 m langen Felsstreifen allmonatlich entfernt; insgesamt wurden dabei etwa 3000 Individuen abgesammelt. Ein Jahr nach Beginn des Absammelns betrug die mittlere Siedlungsdichte der jungenLaminaria hyperborea auf dem von Seeigeln freigehaltenen Felsstreifen 22,7/m2. In den folgenden Jahren wurden zwei- und dreijährigeL. hyperborea nur auf diesem Felsstreifen oder in der Nähe seiner Begrenzungen gefunden. Andere Algenarten reagierten in ähnlicher Weise. Aus den Befunden wird gefolgert, daß die untere Verbreitungsgrenze vonL. hyperborea zumindest zum Teil durch Seeigelfraß bestimmt wird, und daßE. esculentus die Siedlungsdichte der anderen Algenarten beeinflußt.相似文献
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The convulsant properties of xanthine amine congener (XAC, 8-(4-(2-aminoethyl)-aminocarboxylmethyloxy)phenyl-1,3-dipropylxant hine) are compared to those of caffeine. Male Swiss albino mice were infused with convulsants through a lateral tail vein. Convulsion thresholds (i.e. the amount of convulsants required to elicit convulsions) of 39.8 +/- 2.0 mg/kg (n = 10) and 109.8 +/- 2.3 mg/kg (n = 10) were calculated for XAC and caffeine respectively. Pretreatment of animals with the adenosine receptor agonists 2-chloroadenosine, N6-cyclohexyladenosine or 5'-N-ethylcarboxamido-adenosine (1 mg/kg, i.p., 20 minutes prior to infusion) significantly decreased the seizure threshold of both XAC and caffeine. The adenosine uptake blockers, 6-nitrobenzylthioinosine or dipyridamole (0.25 mg/kg, i.p., 20 minutes prior to infusion) did not significantly affect the seizure threshold to either XAC or caffeine. The benzodiazepine agonist diazepam (5 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to both XAC (p less than 0.05) and caffeine (p less than 0.01), whereas the benzodiazepine antagonist Ro 15-1788 (10 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to caffeine (p less than 0.01), but not XAC. The results suggest that actions at benzodiazepine receptors may be a tenable hypothesis to explain the convulsant actions of caffeine, but not those of XAC. 相似文献
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19.
Teresa Żołądek Anna Chełstowska Rosine Labbe-Bois Joanna Rytka 《Molecular genetics and genomics : MGG》1995,247(4):471-481
Uroporphyrinogen decarboxylase (Uro-d; EC 4.1.1.37), the fifth enzyme in the heme biosynthetic pathway, which catalyzes the sequential decarboxylation of uroporphyrinogen to coproporphyrinogen, is encoded by the HEM12 gene in Saccharomyces cerevisiae. The HEM12 gene is transcribed into a major short mRNA and a minor longer one, approximately 1.35 and 1.55 kb, respectively, in size, and that differ in the 5′ untranslated region. “Uroporphyric” mutants, which have no mutations in the HEM12 gene but accumulate uroporphyrinogen, a phenotype chracteristic of partial Uro-d deficiency, were investigated. Genetic analysis showed that the mutant phenotype depends on the combined action of two unlinked mutations, udt1 and either ipa1, ipa2, or ipa3. ipa1 is tightly linked to HEM12 The mutation udt1 apparently acts specifically on the HEM12 gene, and causes a six to tenfold decrease in the levels of the short HEM12 mRNA, in the β-galactosidase activity of a HEM12-lacZ fusion, in immunodetectable protein and enzyme activity. But heme synthesis is normal and porphyrin accumulation was modest. The mutations ipa1, ipa2, and ipa3 had no phenotype on their own, but they caused an increase in porphyrin accumulation in a udt1 background. This multiplicity of genetic factors leading to uroporphyric yeast cells closely resembles the situation in human porphyria cutanea tarda. 相似文献
20.
S. John Gatley Ding-Wei Yu Joanna S. Fowler Robert R. MacGregor David J. Schlyer Stephen L. Dewey Alfred P. Wolf Thomas Martin Colleen E. Shea Nora D. Volkow 《Journal of neurochemistry》1994,62(3):1154-1162
Abstract: The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-metty/-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3l, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methy/-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methy/-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4′-[N-methy/-11CH3]fluorococaine and 4′-[18F]fluoro-cocaine (prepared by nucleophilic aromatic substitution from [18F]fluoride-and 4′-nitrococaine) were compared with [N-methy/-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4′-fluoroco-caine were equipotent at the dopamine reuptake site, but that 4′-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site. The studies with positron-emitting 4′-fluorococaines thus support the lack of significance of labeled metabolites or of binding to 5-hydroxytryptamine reuptake sites to PET images taken with [N-methy/-11CH3]cocaine. [11C]NC prepared by O-methylation of norbenzoylecgonine gave PET images with preferential uptake in striatum, but slower clearance from all brain regions than [O-methy/-11CH3]cocaine. [11C]BE prepared by N-methylation of norbenzoylecgonine did not show brain uptake. 相似文献