Production of 66Ga and 67Ga at a compact cyclotron.
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Gallium Radioisotopes↗
Biomedical subjects
J Bergman
Publications and source records attributed to J Bergman.
Discriminative stimulus effects of cocaine in squirrel monkeys: involvement of dopamine receptor subtypes.
The involvement of dopamine (DA) receptor subtypes in the discriminative stimulus effects of cocaine was investigated in squirrel monkeys trained to discriminate cocaine from vehicle using a two-lever choice procedure. Lever pressing was maintained under a 10-response fixed-ratio schedule of food presentation. In substitution tests, (-)-cocaine and its high-affinity analogs 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT) and 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane (CCT) engendered dose-related increases in the proportion of cocaine-appropriate responses. Full (97-100%) substitution for the training dose of cocaine was observed with all three drugs, the rank order of potency being: CCT greater than CFT greater than cocaine. DA agonists differing in selectivity for D1 and D2 receptor subtypes [6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3-benzazepine (SKF 81297), 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-3-allyl-[1H]-3- benzazepine (SKF 82958), (+)-4-propyl-9-hydroxynapthoxazine [(+)-PHNO], quinpirole, quinelorane, (-)-4,6,6a,7,8,-12b-hexahydro-7-methyl-indolo[4,3-ab]phen ant hridine (CY 208-243) and (-)-apomorphine] also engendered dose-related increases in cocaine-appropriate responses. However, maximally effective doses of these drugs occasioned an average of only 54 to 77% responses on the cocaine-associated lever and markedly reduced response rates. Combinations of the D1 agonist SKF 81297 and the D2 agonist (+)-PHNO did not engender a consistently higher proportion of cocaine-appropriate responses than did either drug alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Behavioral effects of D1 and D2 dopamine receptor antagonists in squirrel monkeys.
The behavioral effects of dopamine antagonists differing in affinity and selectivity at D1 and D2 dopamine receptors were compared in squirrel monkeys responding under a fixed-interval schedule of stimulus-shock termination. D1-selective antagonists included (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23390; its enantiomer (S)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23388; [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H - benzo(d)naphtho-(2,1-b)azepine], SCH 39166; (R)-7-bromo-8-hydroxyl-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine, R-SKF 83566; (R)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol, R-SKF 83692; 2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol, RS-SKF 83692. D2-selective antagonists included cis-N-(1-benzyl-2-methylpyrrolidine-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide, YM-09151-2, eticlopride, raclopride, haloperidol, risperidone, remoxipride, S-sulpiride and R-sulpiride; nonselective dopamine antagonists were S-butaclamol and chlorpromazine. Regardless of selectivity for D1 or D2 receptors, all drugs produced dose-related decreases in fixed-interval responding. A high degree of stereoselectivity was evident for both D1 antagonists (SCH 23390 and R-SKF 83692 more potent than, respectively, SCH 23388 and RS-SKF 83692) and D2 antagonists (S-sulpiride more potent than R-sulpiride). High doses of the D1 and D2 antagonists also reduced motor activity and impaired coordination in monkeys in the home cage after test sessions.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease.
Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease.
Adult↗
Positron emission tomography demonstrates dopamine D2 receptor supersensitivity in the striatum of patients with early Parkinson's disease.
Striatal dopamine D2 receptor binding was studied in vivo with positron emission tomography in seven patients with early Parkinson's disease using [11C]-raclopride. The patients had unilateral symptoms and none of them had received levodopa treatment. The accumulation of [11C]-raclopride in the striatum was rapid and reached a steady state at approximately 40 min after injection. The binding of [11C]-raclopride was measured in the striatum and cerebellum: The total striatal radioactivity in both hemispheres was counted and the respective striatum/cerebellum ratios were calculated. The striatum/cerebellum ratio of [11C]-raclopride binding was significantly (p less than 0.01) increased in the hemisphere contralateral to the parkinsonian symptoms as compared with the opposite hemisphere. Thus, this study demonstrates that there is denervation supersensitivity in dopamine D2 receptor binding in early Parkinson's disease.
Adult↗
Psychomotor stimulant effects of the stereoisomers of chlorpheniramine.
The behavioral effects of the histamine H1 antagonists d- and l-chlorpheniramine and of the H2 antagonist zolantidine were determined in squirrel monkeys responding under a fixed-interval (FI) 3-min schedule of stimulus-shock termination. Although d-chlorpheniramine is known to be much more potent than l-chlorpheniramine for antagonizing H1 receptor-mediated effects of histamine or displacing [3H]-mepyramine from histamine H1 receptors, similar doses of racemic chlorpheniramine and the d- and l-isomers (3.0-10.0 mg/kg) produced comparable increases in rates of responding. Zolantidine (1.0-17.0 mg/kg) did not alter or, at the highest dose, markedly decreased responding. These findings suggest that the psychomotor stimulant effects of chlorpheniramine involve actions other than the blockade of histamine H1 or H2 receptors. Selected H1 antagonists and cocaine are known to have comparable rate-increasing, reinforcing, and discriminative stimulus effects and, recently, the enantiomers of chlorpheniramine have been shown to displace [3H]-cocaine from binding sites in CNS with approximately equal potency. Possibly, such actions mediate behavioral effects common to H1 antagonists and cocaine.
Animals↗
Yeuhchukene--an indole derivative interacting with guinea pig reproduction.
Natural yuehchukene in doses of 10 mg/kg/day induced a 40% reduction of pregnancies in the guinea pig as compared with controls (p less than 0.05). Yuehchukene also caused a reduction in litter size which, however, was not significant indicating limited toxicity of the drug. An inhibition of ovum fertilization and/or implantation is suggested as the mechanism of action.
Animals↗
Tuberculous epididymitis: a case report.
Tuberculous infections of the male genital tract are very uncommon in Australasia. A case of isolated epididymal tuberculosis following a prolonged latent period is presented and the pathogenesis and treatment is discussed.
Antitubercular Agents↗
Electrophysiological investigation of the amino acid carrier selectivity in epithelial cells from Xenopus embryo.
The electrical responses induced by external applications of neutral amino acids were used to determine whether different carriers are expressed in the membrane of embryonic epithelial cells of Xenopus laevis. Competition experiments were performed under voltage-clamp conditions at constant membrane potential. Gly, L-Ala, L-Pro, L-Ser, L-Asn and L-Gln generate electrical responses with similar apparent kinetic constants and compete for the same carrier.They are [Na]o and voltage-dependent, insensitive to variations in [Cl]o and [HCO3]o, inhibited by pHo changes, by amiloride and, for a large fraction of the current, by MeAIB. The increase in [K]o at constant and negative membrane potential reduces the response, whereas lowering [K]o augments it. L-Leu, L-Phe and L-Pro appear to compete for another carrier. They generate electrogenic responses insensitive to amiloride and MeAIB, as well as to alterations of membrane potential, [Na]o and [K]o. Lowering [Cl]o decreases their size, whereas increasing [HCO3]o at neutral pHo increases it. It is concluded that at least two and possibly three transport systems (A, ASC and L) are expressed in the membrane of the embryonic cells studied. An unexpected electrogenic character of the L system is revealed by the present study and seems to be indirectly linked to the transport function. L-Pro seems to be transported by system A or ASC in the presence of Na and by system L in the absence of Na. MeAIB induces an inward current.
Amino Acid Transport Systems↗
Interaction of ellipticine and an indolo[2,3b]-quinoxaline derivative with DNA and synthetic polynucleotides.
The non-covalent DNA interaction of the anticancer drug ellipticine (Scheme I, 1a) as well as an indolo[2,3-b]-quinoxaline derivative (Scheme I, 3b) with a dimethylaminoethyl side chain has been studied by light absorption, linear dichroism (LD) and fluorescence. Compound 3b (Scheme I) has antitumorigenic as well as antiviral activity. Both compounds bind to DNA or synthetic polynucleotides such as poly(dA-dT).(dA-dT) and poly(dG-dC).(dG-dC) by intercalation. In contrast to ellipticine, compound 3b (Scheme I) exhibits a significant binding specificity for alternating AT sequences. Its fluorescence is strongly enhanced in AT sequences and quenched in GC sequences. Fluorescence titrations evaluated as Scatchard plots show that both ellipticine and compound 3b (Scheme I) bind to the nucleic acids according to a non-cooperative neighbor exclusion model.
Alkaloids↗
Effects of a new indole derivative on guinea pig reproduction.
The effect of a new indole derivative, (1,1,3-trimethyl-3-(3'-indolyl)-1,2,3,4-tetra-hydrocyclopent[b]-in dole) denoted 1 related to indomethacin and yeuhchukene 2 were tested on guinea pig reproduction. In mating experiments ten females were given compound 1 p.o. from cycle day 14 and onwards throughout pregnancy. Two groups of ten females each were used as controls. Conception occurred significantly (p less than 0.001) faster in the treatment group. The litter size was significantly (p less than 0.001) smaller after treatment with the indole derivative. Dams and pups did not seem to have been adversely affected by the treatment as judged by their exterior, behavior and survival. The results are suggested to be due to a reduction in the number of ova available for conception (litter size) in combination with improved conditions for ovum implantation and/or a facilitated sperm migration in the female genital tract. These effects are discussed in relation to known effects of arachidonic acid metabolites on reproduction.
Animals↗
Imaging of rats with mammary cancer with two 2-deoxy-2-[18F]fluoro-D-hexoses.
Rats with mammary cancer were imaged by scintigraphy: 10 rats with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 10 rats with [18F]F-D-galactose. The uptake of both tracers was similar in the tumors--the tumor-to-normal tissue ratio was 2.7 +/- 1.1 for [18F]FDG and 2.3 +/- 0.9 for [18F]FDGal at 120 min after injection. In addition to the tumors [18F]FDG accumulated in the brain, bladder and heart, [18F]FDGal in the brain, bladder and liver. [18F]FDGal may be useful for tumor imaging in man; further studies should be addressed to elucidate the mechanism of [18F]FDGal uptake into tumors.
9,10-Dimethyl-1,2-benzanthracene↗
Interactions of rutaecarpine alkaloids with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver.
Rutaecarpine alkaloids have the capacity to inhibit specific 2,3,7,8-[1,6-3H]tetrachlorodibenzo-p-dioxin (TCDD) binding in rat liver cytosol, as analysed by electrofocusing in polyacrylamide gel. The IC50 value for binding of 7,8-dehydrorutaecarpine was estimated to approximately 7 nM indicating a high-affinity interaction, whereas rutaecarpine appeared less active (IC50 approximately 110 nM). These findings are of interest in view of the fact that analogues to these compounds may be formed following UV-irradiation of tryptophan and that such photo-products have been suggested to constitute (the) endogenous ligand(s) for the TCDD receptor. As further support of this notion, the rutaecarpine alkaloids investigated could be fitted into a rectangle of 6.8 x 13.7 A, a characteristic common for most high affinity ligands of the TCDD receptor hitherto studied. In view of their structural similarity to dehydrorutaecarpine and the agreement of their mol. wt with that of the photoproduct with the highest affinity for the TCDD receptor, we suggest deaza-analogues of dehydrorutaecarpine to represent possible candidates for the endogenous TCDD receptor ligand.
Alkaloids↗
Transcutaneous electrical nerve stimulation in the relief of primary dysmenorrhea.
The purpose of this study was to replicate a previous study to determine the effectiveness of acupuncture-like transcutaneous electrical nerve stimulation in treating primary dysmenorrhea. Twenty-one women with dysmenorrhea received a placebo pill or 30 minutes of acupuncture-like TENS. All subjects completed two pain questionnaires before treatment; immediately posttreatment; 30, 60, 120, and 180 minutes posttreatment; and the next morning upon awakening. Each woman also participated in a separate study measuring electrical resistance at four auricular acupuncture points before and immediately after treatment. The data were analyzed with a two-factor repeated-measures analysis of variance, which revealed statistical significance over time but not for group or interaction between group and time. Results revealed an average pain relief of at least 50% immediately posttreatment, indicating that acupuncture-like TENS may be useful for dysmenorrheic pain. This study also suggests that auriculotherapy via acupressure may relieve the pain of primary dysmenorrhea.
Acupuncture Therapy↗
Effects of immunosuppressive chemicals on lymphoid development in foetal thymus organ cultures.
A murine foetal thymus organ culture system was employed to screen a number of immunotoxic chemicals for direct thymus toxicity. The toxic effects caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its congeners on the system used had previously been shown to be similar to those caused in vivo on lymphoid development. The most potent compound tested was the corticosteroid fluocinolone acetonide, which caused a 50% inhibition of lymphoid development (EC50) at a concentration of 5 x 10(-11) M. The EC50 of TCDD was around 5 x 10(-10) M while that of 4 beta-phorbol 12-myristate 13-acetate (TPA) was ca 10(-7) M. TCDD and its congeners are believed to act via binding to the Ah receptor. Other known or presumed ligands of this receptor, which are potent inducers of P1-450 (P-448) -dependent polysubstrate monooxygenase activities, were considerably less toxic with EC50 levels varying between 10(-5) M (7,12-dimethylbenz(alpha-) antracene, alpha-naphthoflavone, benzo(alpha)pyrene) and 10(-4) M (beta-naphthoflavone and 3-methylcholantrene). Dinaphtho/2,3-b,5,6-b/dioxin and indolo/2,3-b/carbazole showed toxicity at 5 x 10(-6)-10(-5) M and 5 x 10(-5) M respectively. TCDD, TPA, and fluocinolone showed additive effects when added two by two in different combinations. Thus fluocinolone, known to counteract the toxicity and epidermal growth factor (EGF) cell-surface receptor-decreasing activity caused by TPA in other cell types, failed to decrease TPA toxicity in the thymus culture system.
Animals↗
Effects of cocaine and related drugs in nonhuman primates. I. [3H]cocaine binding sites in caudate-putamen.
Specific binding sites for [3H]cocaine were identified in caudate-putamen membranes prepared from nonhuman primate brains (Macaca fascicularis and Saimiri sciureus). Saturation of the sites was determined in competition studies using a fixed concentration of [3H]cocaine (2.7 nM) and increasing concentrations of unlabeled cocaine (1 pM-100 microM). Computer resolution of the shallow displacement curve (nH, 0.58) revealed that a two-component binding model [Kd1, 19.2 nM, maximum binding1 (Bmax1), 28.3 pmol/g of tissue; Kd2, 1120 nM, Bmax2, 431 pmol/g of tissue] was statistically preferred over a one-component model (K.50, 283 nM, Bmax, 471 pmol/g of tissue). Binding of [3H]cocaine was NaCl-dependent, with specific binding reduced by 72% when NaCl (100 mM) was omitted from the incubation medium. [3H]Cocaine was displaced stereoselectively by the enantiomers of cocaine and by the diastereoisomers of cocaine and its phenyltropane analog. Cocaine congeners displaced specifically bound [3H]cocaine with IC50 values ranging from 17 nM to over 100 microM in the following rank order of potency: WIN 35,428 greater than WIN 35,065-2 greater than (-)-cocaine greater than WIN 35,981 greater than (-)-norcocaine greater than WIN 35,140 greater than (+)-cocaine, (+)-pseudococaine greater than 3 alpha-tropanyl-1H-indole-carboxylic acid ester greater than 1 alpha H-3 alpha-5 alpha H-tropan-3-yl-3,5-dichlorobenzoate greater than benzoylecgonine, benzoylnorecgonine and (-)-pseudococaine. Several monoamine uptake inhibitors structurally unrelated to cocaine also displaced [3H]cocaine with IC50 values ranging from 1.6 nM to 50 microM. The rank order of potency was: ( +/- )-trans-3-(3',4'-dichlorophenyl)-N-methyl-1-indanamine greater than mazindol greater than nomifensine greater than methylphenidate 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]- 4-(3-phenylpropyl)piperazine, N-[1-(2- benzo(b)thiophenyl)cyclohexyl]piperidine greater than (-)-cocaine greater than 1-amino-4-phenylbicyclo-[2,2,2]-octane greater than bupropion, nisoxetine greater than desipramine, talsupram greater than citalopram. Other drugs, including the dopamine releasing agent (+)-amphetamine and the dopamine receptor agonists (-)-apomorphine, (+)-4-propyl-9-hydroxy-naphthoxazine, quinpirole and SKF 38393 were weak displacers of [3H]cocaine. Monoamine neurotransmitters also were relatively weak, but dopamine was considerably more potent than either norepinephrine or serotonin.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys.
The self-administration of cocaine was compared with that of bupropion, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, mazindol, methylphenidate and nomifensine, drugs that displace [3H]cocaine from its binding sites and have monoamine uptake inhibiting effects in common with those of cocaine. Squirrel monkeys responded under a second-order fixed-interval schedule of consequent i.v. drug injection, and dose-effect curves were established by determining stable rates of responding maintained by saline and a range of doses of each drug. Cocaine (0.01-0.56 mg/kg/injection), bupropion (0.1-3.0 mg/kg/injection), 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3- phenylpropyl)piperazine-(0.03-1.0 mg/kg/injection), methylphenidate (0.01-0.3 mg/kg/injection) and nomifensine (0.01-0.3 mg/kg) maintained comparable rates and patterns of responding in all subjects, whereas mazindol (0.03-0.3 mg/kg) maintained self-administration behavior in only half the monkeys studied. The present results in conjunction with those of previous studies in squirrel monkeys reveal a close correspondence between the relative potencies of cocaine and related drugs for maintaining i.v. self-administration and for increasing rates of schedule-controlled responding, suggesting that the reinforcing and psychomotor-stimulant effects of the drugs are mediated similarly. The potency relations observed in the present study also agree generally with those observed for displacement of specifically bound [3H]cocaine in monkey caudate-putamen suggesting that the reinforcing effects of cocaine involve its actions at specific recognition sites in brain.
Animals↗
Effects of kappa opioids on schedule-controlled behavior of squirrel monkeys.
The behavioral effects of U50,488 [( trans]-3,4-dichloro-N-methyl-N[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetamide), bremazocine, Mr2266 [(-)-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan] and morphine were compared in squirrel monkeys responding under multiple fixed-ratio fixed-interval (FR FI) schedules of food presentation or stimulus-shock termination. Doses of bremazocine (0.001-0.003 mg/kg), U50,488 (0.03-0.1 mg/kg) and Mr2266 (1.0-3.0 mg/kg) that markedly increased overall rates of FI responding maintained by stimulus-shock termination had little effect on or only decreased overall rates of FI responding maintained by food presentation. Each of the kappa opioids decreased FR responding maintained by either consequence. Morphine (0.03-1.7 mg/kg) only decreased responding under all conditions. Pretreatment with Mr2266 (0.1 mg/kg) produced a 10-fold or more rightward shift in the dose-effect functions for morphine under the two multiple schedules and U50,488 under the multiple schedule of food presentation. A 3-fold higher dose of Mr2266 produced an approximately 10-fold rightward shift in the descending portion of the dose-effect functions for U50,488 and bremazocine under the schedule of stimulus-shock termination but did not appreciably alter their rate-increasing effects. Naltrexone (0.1 mg/kg) antagonized the effects of selected doses of morphine or bremazocine on overall rates of responding under the schedule of stimulus-shock termination. In contrast to its effects in combination with morphine, however, naltrexone (0.1-3.0 mg/kg) did not block alterations in patterns of FI responding produced by bremazocine.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗