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  • 1990-1994  (5,445)
  • 1980-1984  (4,023)
  • 1970-1974  (3,703)
  • Organic Chemistry  (11,351)
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  • 101
    Electronic Resource
    Electronic Resource
    A comparison of the effects of the D1 receptor antagonists SCH 23390 and SCH 39166 on suppression of feeding behavior by the D1 agonist SKF38393 (1994)
    Springer
    Psychopharmacology 113 (1994), S. 328-333 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine ; 5-HT2 ; 5-HT1C ; D1 ; SKF 38393 ; SKF 82958 ; SCH 39166 ; SCH 23390 ; Feeding ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypophagic effect of the D1 receptor agonist SKF 38393 is not dose-dependently antagonized by the D1 antagonist SCH 23390. Moreover, the receptor specificity of this interaction remains in question, since SCH 23390 has significant activity at both 5-HT2 and 5-HT1C receptors, and SKF 38393 also interacts with 5-HT1C receptors. To determine the relative significance of these actions, a comparison was made between the anorectic effects in rats of SCH 23390 (0.1–1.0 mg/kg) and the benzonaphthazepine SCH 39166 (0.1–3.0 mg/kg), a D1 antagonist with negligible affinity for 5-HT sites. Both compounds inhibited food-intake dose-dependently, with SCH 23390 being approximately twice as potent as SCH 39166. Behaviorally inactive and active doses of both antagonists were tested in combination with the D1 agonist SKF 38393 (10–56 mg/kg). Neither antagonist was able to produce more than a marginal attenuation of the agonist-induced hypophagia. This demonstrates that previous failures to reverse the behavioral actions of SKF 38393 by SCH 23390 were not due to specific actions of this particular antagonist. Finally, like SCH 23390, SCH 39166 (0.3 mg/kg) was able to attenuate fully the anorectic effects of the D1 agonist SKF 82958 (1.0 and 3.0 mg/kg), demonstrating that neither compound is intrinsically unable to block D1 receptor-mediated hypophagia. The results demonstrate the generality of the D1 antagonist-mediated effect on feeding and call into question the use of SKF 38393 as a D1 agonist in studies of feeding, and perhaps in other contexts as well.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245205
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  • 102
    Electronic Resource
    Electronic Resource
    Prenatal nicotine exposure increased duration of nicotine-induced analgesia in adult rats (1994)
    Springer
    Psychopharmacology 113 (1994), S. 534-538 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Prenatal ; Analgesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245235
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  • 103
    Electronic Resource
    Electronic Resource
    Methamphetamine exposure during early postnatal development in rats: I. Acoustic startle augmentation and spatial learning deficits (1994)
    Springer
    Psychopharmacology 114 (1994), S. 392-401 
    Details
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Rat ; Postnatal ; Acoustic startle ; Spatial learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methamphetamine (MA) induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received less attention. In this experiment the effects of MA exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-MA (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited augmented acoustic startle and impaired performance in a complex multiple-T water maze. Only the early MA exposure group showed a persistent deficit in weight while only the later MA exposure group showed impaired learning in the Morris hidden platform maze. Effects on locomoter activity are reported in the accompanying article. It was concluded that the effects of MA are both long lasting and stage dependent and involve cognitive as well as arousal functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02249328
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  • 104
    Electronic Resource
    Electronic Resource
    Influence of 5-HT3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats (1994)
    Springer
    Psychopharmacology 114 (1994), S. 611-619 
    Details
    ISSN: 1432-2072
    Keywords: Heroin self-administration ; Rat ; 5-HT ; 2-HT3 receptor antagonists ; Ondansetron ; MDL72222 ; Indirect 5-HT agonist ; Dexfenfluramine ; Opioid reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to examine the effects of the 5-HT3 antagonists ondansetron and MDL72222, and the 5-HT releaser and reuptake inhibitor dexfenfluramine, on intravenous heroin self-administration by Wistar rats. Using separate squads of animals, two separate schedules of heroin reinforcement were used; a relatively low dose (0.03 mg/kg per infusion) made available under a FR5 schedule for 1 h each day, and a moderate heroin dose (0.1 mg/kg per infusion) available under a FR1 schedule for 2 h each day. Following the acquisition of stable levels of responding across days, both naloxone pretreatment (0.25 mg/kg SC) and halving the heroin infusion dose produced increases in operant responding for heroin at each concentration. Neither ondansetron (0.01–1 mg/kg SC) nor MDL72222 (0.1–3 mg/kg SC) pretreatment influenced heroin self-administration. Chronic treatment (5 day) of ondansetron (0.01–0.1 mg/kg) was similarly ineffective. However, dexfenfluramine (0.5–2.5 mg/kg IP) consistently reduced heroin self-administration at doses producing only modest decreases in food responding. These findings are in contrast to place conditioning studies, which show that 5-HT3 antagonists but not indirect 5-HT agonists block a morphine-induced place preference. Reasons for such discrepancies remain to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244992
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  • 105
    Electronic Resource
    Electronic Resource
    Effects of (R)-α-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze (1994)
    Springer
    Psychopharmacology 114 (1994), S. 651-656 
    Details
    ISSN: 1432-2072
    Keywords: (R)-α-Methylhistamine ; Scopolamine ; Histamine ; Cognition ; Water maze ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of (R)-α-methylhistamine ((R)-α-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-α-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-α-MeHA and SCOP, (R)-α-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-α-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244997
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  • 106
    Electronic Resource
    Electronic Resource
    Ethological study of the effects of tetrahydroaminoacridine (THA) on social recognition in rats (1994)
    Springer
    Psychopharmacology 114 (1994), S. 644-650 
    Details
    ISSN: 1432-2072
    Keywords: Social recognition ; Cognition ; Social interaction ; Ethological method ; Tetrahydroaminoacridine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two major difficulties confront ethopharmacological investigations on cognitive abilities such as social recognition in drug-treated animals involved in free social interactions. The first concerns the choice of the most relevant behaviours, those reflecting the cognitive abilities attributed to the animals and assessing the specificity of the drug activity, and those reflecting non-specific drug effects. The second refers to the experimenter's awareness that in contrast to physical objects, social stimuli respond to drug-treated subjects and that their own level of responsiveness may influence the changes of drug-treated subjects' social interest. In addition, their contribution may vary according to the different treatments the drug-treated subjects receive. In examining the effects of tetrahydroaminoacridine (THA) at doses of 0.3, 1 and 3 mg/kg on the ability of adult male rats to recognize previously encountered conspecifics, we attempted to take into consideration such difficulties. A detailed behavioural profile of drug-treated rats was reported to separate specific from non-specific effects of THA. In addition, rats were assigned an index of responsibility for contact which takes into account the interactive dimension of each dyad and allows relevant comparisons between different treatments. The doses of THA which were found to decrease the duration of exploration of a familiar juvenile were also found to decrease the number of contacts initiated by the drug-treated subjects. THA induced a relative increase in body care by comparison to saline treatment. However, it had no effect of locomotor activity and rearing of the subjects. These findings enable dissociation of the effects of THA on cognitive versus non-cognitive processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244996
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  • 107
    Electronic Resource
    Electronic Resource
    Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats (1994)
    Springer
    Psychopharmacology 115 (1994), S. 249-253 
    Details
    ISSN: 1432-2072
    Keywords: Penile erection ; Muscimol ; Baclofen ; Bicuculline ; Picrotoxin ; Phaclofen ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01–0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1–0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244779
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  • 108
    Electronic Resource
    Electronic Resource
    Microcatalepsy and disruption of forelimb usage during operant behavior: differences between dopamine D1 (SCH-23390) and D2 (raclopride) antagonists (1994)
    Springer
    Psychopharmacology 115 (1994), S. 24-30 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH-23390 ; Raclopride ; Response duration ; Catalepsy ; Operant behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an experiment designed to distinguish between the behavioral consequences of treatment with SCH-23390, a D1 dopamine receptor blocker, and raclopride, a D2 antagonist, rats were trained to perform a water-reinforced forelimb operant response. Response rate and the duration of each forelimb contact with the operandum were recorded. In addition, the durations of the rat's visits to the reward well were detected by a photobeam which was blocked by the rat's muzzle as it remained at the reward well. In a between-groups dosing design, separate groups of rats (11–13 rats/group) received SCH-23390 (0, 0.01, 0.02, 0.04, 0.08, 0.12 mg/kg, IP, 30 min) or raclopride (0. 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg, IP, 30 min) for 21 consecutive days. Quantitative analyses indicated that for comparable amounts of operant rate reduction, raclopride had a significantly greater tendency than SCH-23390 to increase the duration of operant responses and to increase the maximum muzzle entry duration (i.e., to induce microcatalepsy). The results support the idea that at relatively low doses D2 antagonism is more likely than D1 antagonism to produce effects identified preclinically with extrapyramidal side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244747
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  • 109
    Electronic Resource
    Electronic Resource
    Behavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety (1994)
    Springer
    Psychopharmacology 116 (1994), S. 56-64 
    Details
    ISSN: 1432-2072
    Keywords: Anxiety ; Elevated zero-maze ; Rat ; Diazepam ; Chlordiazepoxide ; mCPP ; 8-OH-DPAT ; Ondansetron ; Head dips ; Stretched attend postures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The elevated “zero-maze” is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125–0.5 mg/kg) and chlordiazepoxide (0.5–2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drugm-chlorophenyl-piperazine (mCPP; 0.25–1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001–0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001–1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel “zero-maze” design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244871
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  • 110
    Electronic Resource
    Electronic Resource
    Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats (1994)
    Springer
    Psychopharmacology 116 (1994), S. 237-241 
    Details
    ISSN: 1432-2072
    Keywords: SR 48692 ; Neurotensin receptor antagonist ; Dopamine ; Apomorphine ; Bromocriptine ; (+) SKF 38393 ; (+) Amphetamine ; Turning ; Yawning ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04 – 0.64 mg/kg orally), antagonizes (50–65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 µg), (+) SKF 38393 (0.1 µg), bromocriptine (0.01 ng) or (+) amphetamine (10 µg) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245067
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  • 111
    Electronic Resource
    Electronic Resource
    Atropine effects on the intermediate stage and paradoxical sleep in rats (1994)
    Springer
    Psychopharmacology 116 (1994), S. 304-308 
    Details
    ISSN: 1432-2072
    Keywords: Intermediate stage of sleep ; Paradoxical sleep ; Spindle ; Theta rhythm ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paradoxical sleep (PS) in the rat, cat and mouse is preceded and sometimes followed by a short-lasting intermediate stage (IS) characterized by high amplitude cortical spindles and low frequency theta rhythm. This stage, which is mimicked by an intercollicular transection, is massively extended at the expense of PS by low doses of barbiturates. Since the pontine cholinergic cell activation of PS is suppressed by barbiturates, we studied whether atropine, an antimuscarinic compound, extends IS at the expense of PS. Atropine sulfate was given at 5, 10 and 20 mg/kg IP. All doses increased dose dependently the occurrence latency of IS and PS. The amount of IS and PS was decreased for several hours, principally by a decrease of the number of phases. At 20 mg/kg the phase mean duration of IS and PS was also decreased. Consequently, IS and PS are similarly supported by muscarinic processes. The theta rhythm frequency was scored during IS and outside PS phasic motor activities (type 2 theta). At all doses it was significantly increased for hours. The theta rhythm frequency was also transiently increased during the hypersynchronization periods of PS (type 1 theta). At 20 mg/kg it was similarly the case for type 1 theta rhythm during waking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245333
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  • 112
    Electronic Resource
    Electronic Resource
    Investigations of fetal development models for prenatal drug exposure and schizophrenia. Prenatald-amphetamine effects upon early and late juvenile behavior in the rat (1994)
    Springer
    Psychopharmacology 116 (1994), S. 226-236 
    Details
    ISSN: 1432-2072
    Keywords: Fetus ; Prenatal drug exposure ; Schizophreniad-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent evidence suggests that mid-pregnancy is a critical period for production of fetal abnormalities that cause behavioral and neuropathological changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11–14 withd-amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period, postnatal days (PND) 20–30, female AM offspring initially showed reductions in rearing, holepoking, and midfield activity. On later trials, and as young adults, AM females showed signs of locomotor hyperactivity despite continued poor foraging efficiency, and were also more sensitive to a 1.0 mg/kgd-amphetamine challenge. AM males showed initially slower and more perseverative responding than controls, but then developed excessive response switching. These changes continued during tests for Retention, Reversal, and Extinction in the Late Juvenile/Early Adult stage (PND 50–90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning preference (right or left), and slower reversal learning than controls. Behavioral data were consistent with aberrations in thalamo-frontal and mesolimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245066
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  • 113
    Electronic Resource
    Electronic Resource
    Chronic haloperidol treatment leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum (1994)
    Springer
    Psychopharmacology 116 (1994), S. 279-284 
    Details
    ISSN: 1432-2072
    Keywords: Adenosine A2 receptor ; Dopamine D2 receptor ; Methylxanthine ; Tardive dyskinesias ; Receptor-receptor interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists. The data showed that: (i) haloperidol pretreatment causes a higher binding of the D2 antagonist [3H] raclopride in striatal membrane preparations due to an increase in the number of D2 receptors without changes in their affinity for the antagonist (increase in Bmax without changes in kd); (ii) GCS 21680 decreases the affinity of dopamine for the D2 receptor, by increasing the equilibrium dissociation constants of high (Kh) and low affinity (K1) dopamine D2 binding sites and increases the proportion of high affinity binding sites (Rh); (iii) a low dose of CGS 21680 (3 nM), which is ineffective in membrane preparations from neostriatum of nontreated animals, is effective in membranes from the striatum of haloperidol-pretreated animals; (iv) the nonselective adenosine antagonist theophylline (20 mg/kg SC) causes a higher motor activation in rats pretreated with haloperidol. The possible relevance of these results for the pathophysiology and treatment of tardive dyskinesias is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245329
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  • 114
    Electronic Resource
    Electronic Resource
    Adrenalectomy increases local cerebral blood flow in the rat hippocampus (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 183-188 
    Details
    ISSN: 1432-2013
    Keywords: Hippocampus ; Corticosterone ; Adrenalectomy ; Local cerebral blood flow ; Diurnal rhythm ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H2 clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374770
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  • 115
    Electronic Resource
    Electronic Resource
    Exercise-induced necrotic muscle damage and enzyme release in the four days following prolonged submaximal running in rats (1994)
    Springer
    Pflügers Archiv 428 (1994), S. 346-351 
    Details
    ISSN: 1432-2013
    Keywords: Skeletal muscle ; Muscle damage ; Treadmill running ; Serum ; Enzymes ; Water content ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Wistar rats were made to run uphill on a treadmill 5.5° incline at 17 m min−1 for 4 h, and killed for muscle and serum sampling 2, 4, 12, 24, 48 or 96 h after the exertion. To estimate the degree of muscle damage,β-glucuronidase activity, total protein concentration, water content and morphology were examined in the red parts of quadriceps femoris (MQF) and soleus (MS) muscles, the distal white part of the rectus femoris muscle (MRF) and the superficial part of triceps brachii muscle (MTB). Simultaneous serum samples were assayed for creatine kinase (CK) activity and carbonic anhydrase III (CA III) concentration. Fibre swelling and interstitial oedema were detected in MS at 4 h and in MQF at 12 h and typical histopathological changes, including inflammation and fibre necrosis, in both muscles 12–96 h post-exertion.β-Glucuronidase activity, a quantitative marker of muscle damage, was increased in MS at 4 h, in MQF at 24 h and in MRF 48 h after the running. No increase occurred in MTB. Water and protein content increased or decreased respectively, faster in MS (2 h post-exercise) than in MQF (12 h) or MRF (12 h). Water content thus contributed to muscle damage by preceding the increase inβ-glucuronidase activity. Serum CK activity was increased 2, 4, and 48 h after the running. Changes in serum CA III concentration were rather similar to those in CK but were not significant. The increase in serum CK was not in concert with the necrotic events in the muscle but occurred considerably earlier (2 h vs. 12–24 h post-exercise). The second peak in CK, 48 h post-exercise (during the necrotic phase), was smaller than the first one. Our results show that serum CK activity is an inaccurate estimate of exercise-induced muscle damage as regards interpretation of the degree and the time course of pathological events in the muscle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00724517
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  • 116
    Electronic Resource
    Electronic Resource
    An interaction between glucose and estrogen in gastric acid secretion in the lateral hypothalamic area of female rats (1994)
    Springer
    Experimental brain research 102 (1994), S. 171-174 
    Details
    ISSN: 1432-1106
    Keywords: Estrogen ; Gastric acid secretion ; Glucose ; Hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastric acid outputs caused by glucose injection into the lateral hypothalamic area (LHA) were examined in insulin hypoglycemia with or without estradiol-17β (EST) administration in bilaterally ovariectomized (OV) female rats. The basal level of acid output was higher in OV rats without EST than in OV rats with EST. When acid response was expressed as the percentage change, glucose injection into the LHA decreased acid output in a dose-dependent fashion in OV rats, while, in OV rats with EST, glucose injection into the LHA also reduced acid output without dose dependency. It was also noted that the threshold concentration of glucose that induced an acid response was lower in OV rats without EST than in OV rats with EST. These findings suggest that glucose-sensitive neurons responsible for gastric acid secretion can be modulated by estrogen at the LHA level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00232450
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    Subthreshold rectification in neostriatal spiny projection neurons (1994)
    Springer
    Experimental brain research 100 (1994), S. 239-249 
    Details
    ISSN: 1432-1106
    Keywords: Neostriatum ; In vitro brain slices Inward rectification ; Subthreshold ion conductances Firing pattern ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intracellular recordings from slice preparations were used to assess the subthreshold electrophysiological behavior of rat neostriatal projection neurons. Both current steps and ramp currents were used to estimate the current-voltage relationship (I–V plot). Inward rectification in the subthreshold range was a characteristic of most neurons. The amount of rectification varied greatly, and it was complex: membrane voltage trajectories in response to ramps were made up by almost piecewise changes in the rate of voltage rise, suggesting that multiple conductances contribute to the subthreshold range. Inward current blockers such as tetrodotoxin (TTX) or Cd2+ decreased inward rectification, whereas outward current blockers such as tetraethylammonium (TEA) or 4-aminopyridine (4-AP) increased inward rectification. However, most inward rectification was due to TEA- and Cs+-sensitive conductances and not to TTX- or Cd2+-sensitive conductances. Cs+-sensitive conductances predominated at more negative membrane potentials, whereas 4-AP-sensitive conductances predominated at just ±10 mV below the firing threshold. In spite of a very slow activation, there was evidence for transient outward currents modulating the response, i.e., 4-AP-sensitivity, and voltage-sensitivity for firing frequency and threshold. TEA-sensitive conductances also contributed toward fixing the firing threshold. These results imply the contribution of various ion conductances on the shaping of the characteristic physiological firing recorded in vivo. Modulation of these responses by transmitters or peptides may help to understand neural processing in the neostriatum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227194
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  • 118
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    Re-initiated growth from mature ventral mesencephalon: an in oculo transplant study of nigrostriatal co-grafts (1994)
    Springer
    Experimental brain research 101 (1994), S. 73-85 
    Details
    ISSN: 1432-1106
    Keywords: Substantia nigra ; Striatum ; Transplant Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of mature dopaminergic neurons derived from ventral mesencephalon to re-initiate growth after making contact with a non-innervated target was studied using the intra-ocular grafting model. Foetal ventral mesencephalic tissue or brain stem including the locus coeruleus area was grafted to the anterior chamber of the eye. Two weeks, 6 weeks or 1 year after the first implantation, foetal striatal tissue was placed in contact with the nigral graft or grafted alone. The size of the transplants was measured through the cornea. The final size of the striatal grafts was significantly larger when placed alone than when co-grafted with 1-year-old or 6-week-old dopaminergic grafts. Striatum grafted together with 2-week-old nigra was larger than when grafted adjacent to mature substantia nigra, but not significantly so. Nerve fibre outgrowth into the iris from the nigral transplants did not increase after maturation, but the re-innervated area of the host iris progressively increased around the locus coeruleus grafts. Ingrowth of tyrosine hydroxylase (TH) immunoreactive nerve fibres into the striatal grafts was studied 6 weeks after the second implantation. TH immunohistochemistry revealed innervation of the striatal piece in all cases, except for the group where striatum alone was grafted. With the short survival time for cografts of 6 weeks, TH-positive nerve fibres innervated a larger volume, had a patchy appearance and the density was higher in striatum grafted to 2 week-old nigral transplants than that seen in striatal transplants grafted to mature nigral grafts. The patchy pattern of TH-immunoreactive nerve terminals was also seen in striatum co-grafted with 6-week-old or 1-year-old nigral transplants. No difference in striatal innervation volume was detected between those latter two groups. When striatum was implanted adjacent to mature ventral mesencephalon and grown together for 6 months — the longer survival time — the same dense TH-positive innervation as seen in striatum co-grafted with immature nigral tissue at the shorter survival time was found. Additionally, the nigral part of the co-grafts showed increased TH-immunoreactive nerve fibre density. In conclusion, dopaminergic neurites from mature ventral mesencephalic transplants can re-initiate growth if placed in contact with non-innervated striatal tissue. The nigral grafts do not progressively re-innervate the host iris, while locus coeruleus grafts do. The intra-ocular grafting model can be used to study the in vivo effects of trophic factors on mature dopaminergc neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00243218
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    Threshold-spacing in motoneurone pools of rat and cat: possible relevance for manner of force gradation (1994)
    Springer
    Experimental brain research 102 (1994), S. 69-74 
    Details
    ISSN: 1432-1106
    Keywords: Motoneurone ; Recruitment ; Force modulation ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the context of an analysis concerning factors of importance for the relative contributions of recruitment and rate gradation of muscle force, the distribution of electrical excitability was analyzed for medial gastrocnemius (MG) motoneurones of rat and cat. The experimental data came from previously collected intracellular measurements in animals anaesthetized with pentobarbitone. Electrical excitability was measured as the threshold (nanoamperes) for single spike generation (rheobase) in rat and for maintained repetitive firing (rhythmic threshold) in cat. Furthermore, the data included measurements of axonal conduction velocity and of contractile properties of the muscle units innervated by the studied motoneurones. The units were categorized into types S (slow-twitch, fatigue-resistant), FR (fast-twitch, fatigue-resistant) and FF (fast-twitch, fatiguable) on the basis of the combined criteria of twitch-speed and sensitivity to fatigue. We confirmed that, in spite of the presence of normal-looking symmetrical distributions of axonal conduction velocity, there was a positive skew in the distribution of electrical excitability (relatively high numbers of cells with low thresholds, few with high ones). Within each unit category (S, FR, FF), we ranked the motoneurones according to their relative electrical excitability and calculated the threshold difference between consecutive cells (“threshold spacing”). In accordance with the skewed distribution of electrical excitability, we found that the mean threshold spacing was ranked in the same way as the mean thresholds, i.e. S〈FR〈FF; the statistical analysis showed that, for cats as well as rats, small threshold-spacing steps were significantly more common for S than for FF motoneurones. In the discussion it is pointed out that the narrow threshold-spacing for S units, as compared to FF units, would tend to decrease the relative amount of recruitment-parallel rate modulation in these cells. Thus, the spacing of recruitment thresholds tends to allow the easily recruited S motoneurones to remain firing at relatively low rates during ongoing recruitment gradation, which would be of potential value in promoting a high degree of endurance for long-lasting postural contractions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00232439
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    Sensorimotor transformation in a spinal motor system (1994)
    Springer
    Experimental brain research 100 (1994), S. 170-174 
    Details
    ISSN: 1432-1106
    Keywords: Withdrawal reflexes ; Motion analysis Nociception ; Pain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To use sensory information from the skin to guide motor behaviour the central nervous system must transform sensory coordinates into movement coordinates. As yet, the basic principles of this crucial neural computation are unclear. One motor system suitable as a model for the study of such transformations is the spinal withdrawal reflex system. The spatial organization of the cutaneous input to these reflexes has been characterized, and we now introduce a novel method of motion analysis permitting a quantitative analysis of the spatial input-output relationship in this motor system. For each muscle studied, a “mirror-image” relationship was found between the spatial distribution of reflex gain for cutaneous input and the pattern of cutaneous unloading ensuing on contraction. Thus, there is an “imprint” of the movement pattern on this motor system permitting effective sensorimotor transformation. This imprint may indicate the presence of a learning process which utilizes the sensory feedback ensuing on muscle contraction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227291
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    Expression of major histocompatibility complex class II antigen on amoeboid microglial cells in early postnatal rat brain following intraperitoneal injections of lipopolysaccharide (1994)
    Springer
    Experimental brain research 100 (1994), S. 287-292 
    Details
    ISSN: 1432-1106
    Keywords: Amoeboid microglia Major histocompatibility complex Type 3 complement receptor ; Endotoxin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats given two single intraperitoneal injections of lipopolysaccharide (LPS) at 1 and 4 days of age and killed at 7 days of age, 11.5–12% of amoeboid microglial cells (AMC) in the supraventricular corpus callosum were induced to express major histocompatibility complex (MHC) class II antigen, as detected with monoclonal antibody OX-6. The MHC class II antigen induced was colocalized with MHC class I antigen and type 3 complement receptors on the same cells. The expression of MHC class II antigen on the plasma membrane of AMC was confirmed in immunoelectron microscopy. Although OX-6-positive AMC often assumed a perivascular position, the majority of them, however, were far removed from the blood vessels. The cytoplasmic processes of the perivascular OX-6-positive AMC appeared to rest directly on the vascular lamina, and in some section profiles they were in contact with a large surface area of the outer wall of small blood vessels. It is concluded from this study that although MHC class II antigen is not constitutively present on AMC, it is, however, inducible under stimulation with LPS. It is, therefore, suggested that the OX-6-positive AMC, especially the perivascular AMC, may have the potentiality to function as antigen-presenting cells in the developing brain when challenged by LPS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227198
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    Lowering of extracellular pH suppresses low-Mg2+-induces seizures in combined entorhinal cortex-hippocampal slices (1994)
    Springer
    Experimental brain research 101 (1994), S. 44-52 
    Details
    ISSN: 1432-1106
    Keywords: Acidosis ; Seizures ; Brain slices ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lowering [Mg2+]o induces epileptiform bursting in hippocampus and entorhinal cortex (EC), presumably by activation of N-methyl-d-aspartate (NMDA) receptors. Since increasing [H+]o has been shown to reduce NMDA receptor activation, we hypothesized that this could contribute to anticonvulsant actions of acidic pH. To test this, we studied the effects of raising extracellular PCO2 (20.6%, pH = 6.7) or lowering extracellular pH (6.7 or 6.2) on low-Mg2+-induced epileptiform discharges. Lowering the pH to 6.7 by either means increased the interval between seizure-like events (SLEs), decreased the maximal amplitude of SLEs, and, if the site of seizure generation was at a distance from the recording site, acidification slowed the rate of seizure propagation. In contrast, the duration of SLEs was unaffected by acidic pH or high PCO2. Raising PCO2 or lowering pH to 6.7 also blocked early (8–10 min) but not late (〉 20 min) phases of status-like discharges. All effects of the extracellular pH changes were fully reversible. Further lowering of extracellular pH to 6.2 completely and reversibly blocked both SLEs and status-like discharges. Our data show that the effects of high PCO2 and low pH on seizures in the EC in vitro may be dose-dependent and consistent with induction by proton blockade of NMDA receptors. Thus, blockade of NMDA currents by protons may be an important component of the anticonvulsant action of extracellular acidosis. The results also suggest that acidosis may be a desirable property for new antiepileptic treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00243215
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    Phosphinic acid derivatives as baclofen agonists and antagonists in the mammalian spinal cord: an in vivo study (1994)
    Springer
    Experimental brain research 101 (1994), S. 59-72 
    Details
    ISSN: 1432-1106
    Keywords: Spinal cord ; Synaptic transmission ; GABAB receptors ; Baclofen agonists and antagonists ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre-and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35 348, 36 742, 46 381, 52 432, 54 626 and 55 845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABAA agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre-and postsynaptic inhibitory effects of 3-aminopropyl-methyl-osphinic acid (CGP 35 024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35 024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABAB receptors. Spinal pre-and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55 845 and 46 381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00243217
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    Synaptic connectivity of serotonin graft efferents in the suprachiasmatic and supraoptic nuclei of the hypothalamus (1994)
    Springer
    Experimental brain research 101 (1994), S. 353-364 
    Details
    ISSN: 1432-1106
    Keywords: Transplantation ; Serotonin neurons ; Hypothalamus ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo-or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227329
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  • 125
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    Ibotenic acid lesions of the striatum reduce drug-induced rotation in the 6-hydroxydopamine-lesioned rat (1994)
    Springer
    Experimental brain research 101 (1994), S. 365-374 
    Details
    ISSN: 1432-1106
    Keywords: 6-Hydroxydopamine ; Ibotenic acid ; Rotation ; Amphetamine ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lesions of the dopaminergic nigrostriatal tract produce a range of motor and sensorimotor deficits. One of the simplest and most reliable is the rotational response of the animal following activation with drugs that stimulate the dopaminergic network, most notably amphetamine and apomorphine. Consequently, the rotation test has been extensively used in assessing the success of treatments designed to restore dopaminergic function, including neural transplants. The present study investigates whether rotation induced by 6-hydroxydopamine lesions of the nigrostriatal bundle in rats is modified by additional lesions in the neostriatum. It was found that apomorphine-induced rotation can be reduced by ibotenic acid lesions of the dopamine-deafferented striatum, and that the extent of the reduction was proportional to the size of the lesions. In contrast, such lesions produced a non-significant reduction in amphetamine-induced rotation, although the correlation between the extent of the reduction and the size of the lesion was again apparent. Since the pattern of change was similar in direction, albeit smaller in magnitude, than the previously reported effects of intrastriatal transplantation in rats with similar nigrostriatal lesions, rotation tests alone do not provide an unequivocal test of graft survival and function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227330
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    Metabolism of a glucuronide conjugate of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats (1994)
    Springer
    Archives of toxicology 69 (1994), S. 14-17 
    Details
    ISSN: 1432-0738
    Keywords: Key words Tobacco-specific nitrosamine ; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone ; [4-(Methylnitrosamino)-1-(3-pyridyl)but-1-yl]- β-O-d-glucosiduronic acid ; Rat ; Urine ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-β-O-d-glucosiduronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke. In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2±3.1% of the total radioactivity; the remaining part of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6±1.7%) and its α-hydroxylation (11.5±2.2%) and N-oxidation (3.6±1.6%) products. The presence of α-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite may be activated in vivo to carcinogenic intermediates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050130
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    Messenger RNA levels of lung extracellular matrix proteins during ozone exposure (1994)
    Springer
    Lung 172 (1994), S. 15-30 
    Details
    ISSN: 1432-1750
    Keywords: Rat ; DNA ; mRNA ; Collagen ; Fibronectin ; c-myc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continuous exposure of rats to ozone has been shown to result in lung epithelial damage, inflammation, and subsequent increases in collagen content. The main goal of this study was to identify the earliest time point of altered extracellular matrix protein gene expression by utilizing Northern blot analyses of rat lungs continuously exposed to 1.0 ppm ozone for 14 days. An early increase of steady-state fibronectin mRNA levels was observed at 2 days of exposure, prior to the time point of increased type I collagen mRNA, which was seen at 4 days. This increased level of type I collagen mRNA preceded measurable changes in total lung collagen content, observed at 7 days. In addition, peak levels of the growth-related proto-oncogene c-myc mRNA could be correlated with maximal increases of lung DNA content, although the initial increase in c-myc mRNA preceded measurable changes of total lung DNA. The use of specific cDNA probes for measuring altered gene expression can be useful for defining the early cellular and molecular events in ozone-induced lung injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00186166
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    High-resolution magnetic resonance imaging of arthritic pathology in the rat knee (1994)
    Springer
    Skeletal radiology 23 (1994), S. 429-437 
    Details
    ISSN: 1432-2161
    Keywords: Arthritis ; Rat ; Knee ; MRI ; X-radiography ; histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract High-resolution magnetic resonance imaging (MRI) has been used to visualise the changes that occur in both soft tissue and bone during antigen-induced, monoarticular arthritis (AIMA) of the rat knee. Extensive optimisation studies were performed in order to minimise the time of the experiments and to maximise both the signal-to-noise ratio and the contrast in the MR images. The study was cross-sectional rather than longitudinal and at each of the 13 time points studied during the progression of the disease, corresponding X-radiographs and histological sections were obtained. Interpretation of the spin echo MR images was aided by the use of chemical shift-selective imaging, magnetisation transfer contrast and relaxation time experiments, as well as by correlation with the histology and X-radiography data. The MR images clearly show invasion of the synovium by an inflammatory pannus which spreads over the articular cartilage and invades the bone, leading to erosion and later remodelling. Two distinct types of bony erosion were observed: focal erosions, especially at the margins of the joint, and subchondral erosions. It is concluded that MRI provides a sensitive, non-invasive method for investigating both early-stage inflammatory changes and late-stage bony changes in the knee joints of the arthritic rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00204603
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    Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex (1994)
    Springer
    Psychopharmacology 113 (1994), S. 487-492 
    Details
    ISSN: 1432-2072
    Keywords: Prefrontal cortex ; Dopamine ; Acoustic startle response ; Prepulse inhibition ; 6-Hydroxydopamine ; Rat ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 × 1 µl per side) of vehicle, a low (3.0 µg/µl) or a high (6.0 µg/µl) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245228
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    Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with the fixed-interval peak procedure (1994)
    Springer
    Psychopharmacology 114 (1994), S. 463-468 
    Details
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Fixed-interval peak procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twelve rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats were then trained for 60 sessions under a discrete-trials fixed-interval schedule (peak procedure). In half the trials, a reinforcer became available 40 s after trial onset, and the trial was terminated upon reinforcer delivery; the remaining trials were 120 s in duration, and reinforcement did not occur in these trials. Performance during the 120-s trials was characterized by increasing response rate during the first 40 s of the trial, declining response rate between 40 s and 80 s, and a secondary increase in response rate during the final 40 s of the trial. The lesioned group showed a broader “spread” of the response rate function than the control group (time between attainment of 70% of the peak response rate and subsequent decline of response rate below this level); however, the peak response rate and the time from trial onset until attainment of the peak response rate did not differ significantly between the groups; the spread/peak-time ratio was significantly greater in the lesioned group than in the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02249337
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    Crossmodal divided attention in rats: effects of chlordiazepoxide and scopolamine (1994)
    Springer
    Psychopharmacology 115 (1994), S. 213-220 
    Details
    ISSN: 1432-2072
    Keywords: Divided attention ; Scopolamine ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract “Divided attention” is a psychological construct that hinges on assumptions about a fixed finite capacity of subjects to simultaneously process multiple sets of information. A model of a crossmodal divided attention task was developed in rats. Initially, rats were trained consecutively in operant auditory and visual conditional discrimination tasks. The final task consisted of two successive blocks of 20 trials per modality (modality certainty), followed by 60 trials comprising a semi-randomized sequence of stimuli of both modalities (auditory or visual) and qualities (flashing/pulsing or constantly turned on; modality uncertainty). In comparison to unimodal blocks of trials, performance in the mixed condition was assumed to reflect the demands on the parallel processing of two sets of stimulus-response rules. While response accuracy remained unchanged, response latencies were generally longer in the bimodal condition. Administration of scopolamine (0.03, 0.06, 0.1 mg/kg) or chlordiazepoxide (1, 3, 5, 8 mg/kg) dose-dependently increased response latencies. The scopolamine-induced increase in response latencies was greater in the mixed condition. Cost-benefit analyses demonstrated that the absolute divided attention costs (in ms) were generally higher for visual than for auditory stimuli. Both drugs produced qualitatively similar effects; however, scopolamine was more potent in increasing the absolute divided attention costs than chlordiazepoxide. These data are discussed in terms of the validity of this animal paradigm, and of hypotheses about the effects of benzodiazepine receptor agonists and muscarinic antagonists on brain information processing capacity.
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    URL: http://dx.doi.org/10.1007/BF02244774
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    Diazepam impairs place learning in naive but not in maze-experienced rats in the Morris water maze (1994)
    Springer
    Psychopharmacology 115 (1994), S. 73-78 
    Details
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Diazepam ; Morris water maze ; Place learning ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244754
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    α2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats (1994)
    Springer
    Psychopharmacology 115 (1994), S. 478-484 
    Details
    ISSN: 1432-2072
    Keywords: Aggression ; α2 Adrenoceptors ; Catecholamines ; ACTH ; Corticosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245571
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    Effects of cocaine microinjections into the nucleus accumbens and medial prefrontal cortex on schedule-induced behaviour: comparison with systemic cocaine administration (1994)
    Springer
    Psychopharmacology 115 (1994), S. 375-382 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Schedule-induced polydipsia ; Drinking ; Locomotor activity ; Nucleus accumbens ; Medial prefrontal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cocaine HCl infusions into either the nucleus accumbens (NACC) or medial prefrontal cortex (PFC) were compared on the performance of schedule-induced polydipsia (SIP) and related behaviours. Food-deprived rats were exposed to a fixed-time 60-s schedule of food delivery in daily 30-min sessions until stable levels of behaviour were obtained (14 days). Rats were then bilaterally infused with cocaine into either the NACC or PFC via chronically indwelling guide cannulae. Each subject received a sequence of five cocaine infusions (0, 12.5, 25, 50, 100 µg) according to a Latin Square design. For comparison, following these intracranial infusions each rat received a sequence of five IP injections of cocaine (0, 2.5, 5, 10, 20 mg/kg) also in a counterbalanced order. NACC and PFC infusions of cocaine and IP cocaine dose-dependently reduced SIP. Cocaine infusions into the NACC, but not the PFC, increased locomotor activity but the characteristic temporal profile of locomotor activity during SIP was retained. IP cocaine also increased locomotor activity in a dose-dependent manner, but the temporal profile of activity was flattened following 20 mg/kg cocaine. NACC and PFC infusions of cocaine had little effect on the total number of panel presses to gain access to the food pellets, but did slightly decrease the high rates of responding immediately prior to the pellet delivery. IP cocaine increased the total number of panel presses at the higher doses, mainly by increasing the low rates of responding. The effects of cocaine infusions into the PFC were behaviourally the most selective, as they reduced SIP without having substantial effects either on locomotor activity or panel pressing. These data therefore implicate a role for the PFC in the performance of SIP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245080
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    CCK-A and CCK-B selective receptor agonists and antagonists modulate olfactory recognition in male rats (1994)
    Springer
    Psychopharmacology 115 (1994), S. 435-440 
    Details
    ISSN: 1432-2072
    Keywords: Behaviour ; Olfactory recognition ; Social investigation ; Neuropeptides ; Cholecystokinin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modulation of learning and memory is one of the physiological roles that the neuropeptide cholecystokinin (CCK-8) may play. We have used a behavioural model of olfactory recognition among rats to test this hypothesis and to explore the relationship between CCK-A and CCK-B receptors and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of investigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were evaluated as the persistence in investigation 30 min and the decrease in investigation 120 min after pharmacological manipulations, respectively. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY-262691) enhanced olfactory recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous evidence of the detrimental effect of the non-peptide CCK-A antagonist devazepide on olfactory recognition, these results confirm and extend the hypothesis that there is a balance between CCK-A-mediated facilitative effects and CCK-B-mediated inhibitory effects on memory retention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245565
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    Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine (1994)
    Springer
    Psychopharmacology 115 (1994), S. 441-446 
    Details
    ISSN: 1432-2072
    Keywords: Chronic mild stress ; Imipramine ; Animal model of depression ; Dopamine ; D1-receptors ; D2-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245566
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    Methamphetamine exposure during early postnatal development in rats: II. Hypoactivity and altered responses to pharmacological challenge (1994)
    Springer
    Psychopharmacology 114 (1994), S. 402-408 
    Details
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Rat ; Postnatal development ; Hypoactivity ; Pharmacological challenge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methamphetamine induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received little attention. In this experiment the effects of methamphetamine exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-methamphetamine (d-MA) (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited reduced locomotor activity. The effect was most evident at 30 days of age and was smaller at 45 and 60 days and only present at these latter ages in males. Only the early MA exposure group showed prolonged suppression of activity in response to a challenge dose of fluoxetine and a persistant deficit in weight while only the later MA exposure group showed attenuated suppression of activity in response to a challenge dose of fluoxetine. Based both on the present data and those in the preceding article, it was concluded that the effects of MA are both long lasting and stage dependent and involve arousal as well as cognitive functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02249329
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    5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task (1994)
    Springer
    Psychopharmacology 116 (1994), S. 135-142 
    Details
    ISSN: 1432-2072
    Keywords: Short term memory ; Delayed matching to position ; 5-HT ; 5-HT1A receptor ; 8-OH DPAT ; Ipsapirone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245055
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    The neurosteroid pregnenolone sulfate blocks NMDA antagonist-induced deficits in a passive avoidance memory task (1994)
    Springer
    Psychopharmacology 116 (1994), S. 201-206 
    Details
    ISSN: 1432-2072
    Keywords: Neurosteroid ; Memory ; Amnesia ; NMDA receptor ; Ataxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84–1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84–840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245063
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    Dissociation between brown adipose tissue thermogenesis and sympathetic activity in rats with high plasma levels of oestradiol (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 40-43 
    Details
    ISSN: 1432-2013
    Keywords: Brown adipose tissue ; Cold-acclimation ; Noradrenaline turnover ; Oestradiol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown previously that high plasma levels of oestradiol inhibit brown adipose tissue thermogenesis. Since rats and mice show a close association between thermogenic activity in and sympathetic discharge to brown fat, we measured the noradrenaline turnover in rats with high plasma levels of oestradiol to establish whether the observed inhibition of thermogenic activity is brought about by a reduction in the sympathetic drive to brown adipocytes. Oestradiol-filled Silastic capsules were implanted subcutaneously in female rats previously acclimated either to thermoneutrality or to cold. Control rats received empty implants. After 15 days treatment, noradrenaline turnover was measured by blocking its synthesis with α-methyl-p-tyrosine. As expected, noradrenaline turnover was higher in cold-acclimated rats than in rats kept at thermoneutrality. The presence of high plasma oestradiol levels did not alter sympathetic activity in any of the treated groups despite reducing thermogenic activity. This result reveals that oestradiol dissociates the thermogenic activity of brown adipose tissue from its sympathetic activation. Such dissociation has never been previously reported in rats, although it seems to be common in Syrian hamsters. However the causative factor in this species is unknown.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374668
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    Respiratory responses to combined hypoxia and hypothermia in rats after posterior hypothalamic lesions (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 371-377 
    Details
    ISSN: 1432-2013
    Keywords: Body temperature ; Respiration ; Electrolytic lesions ; Urethrane anaesthesia ; Hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (T bc) was maintained within the normal range (37–38° C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n=6) or posterior hypothalamus (n=6). Neither lesion altered respiration while rats breathed air at either T bc. At normal T bc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced T bc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00388299
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    Effects of methionine sulphoximine treatment on renal amino acid and ammonia metabolism in rats (1994)
    Springer
    Pflügers Archiv 427 (1994), S. 524-532 
    Details
    ISSN: 1432-2013
    Keywords: Glutamine synthetase ; Kidney ; Intestine ; Glutamine ; Ammonia ; Amino acids ; Metabolism ; Rat ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal glutamine metabolism in relation to ammoniagenesis has been extensively studied during chronic metabolic acidosis, when arterial glutamine levels are reduced. However, little is known about the effects of reduced glutamine delivery on renal glutamine and ammonia metabolism at physiological systemic pH values. Therefore, a model of decreased arterial glutamine concentrations at normal pH values was developed using methionine sulphoximine (MSO). Renal glutamine and ammonia metabolism was measured by determining fluxes and intracellular concentrations after an overnight fast in ether anaesthetized normal rats, MSO-treated rats and their pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids were determined concomitantly. After 2 and 4 days of MSO treatment, arterial glutamine concentrations were reduced to 55%, while arterial ammonia concentrations increased by 70%. Kidney glutamine uptake reduced, but systemic pH was unchanged. Fractional extraction of glutamine remained unchanged, suggesting that also in vivo net uptake of glutamine by the kidney at subnormal levels is related to arterial glutamine concentrations. As a result, at day 2 but not at day 4, the kidney reduced the net release of ammonia into the renal vein and thus reduced net renal ammonia addition to body ammonia pools. Therefore at day 2, the kidney seems to play an important role in adaptation to both hyperammonaemia and hypoglutaminaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374270
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    Analysing ion channels with hidden Markov models (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 328-332 
    Details
    ISSN: 1432-2013
    Keywords: Cortical collecting duct ; K+ channel ; Rat ; Isolated tubule ; Patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ion channel current amplitudes (μ) and open probabilities (P o) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of μ, P o, and mean dwell times (τ) of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e. g. filtering, setting of threshold, fitting processes) are done in one step. Two different K+ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The μ value of the intermediate-conductance K+ channel (i-K+) was 3.9±0.1 pA (SM) and 3.8±0.2 pA (HMM) for 11 observations. The P o value of this channel was 10.2±4.2% (SM) and 10.1±4.0% (HMM). The mean τ values were 5.4±0.6 ms for the open state and 9.6±2.2 ms and 145±21 ms for the closed states (SM) and 7.8±1.1 ms, 7.7±0.9 ms and 148±24 ms (HMM), respectively. For seven small-conductance K+ (s-K+) channels, which were found in the same membrane patches as the i-K+, an accurate analysis of P o and τ was not possible with the SM. The μ value was 1.0±0.1 (SM), 0.9±0.1 (HMM) pA. P o was 16.6±4.6%, the open τ value was 11.1±2.8 ms, and the closed τ value was 34.9±8.5 ms. The HMM allows the analysis of single-channel currents, P o, and mean τ values when different or more than one ion channel(s) are colocalized in one membrane patch. Where analysis with the SM was possible results did not significantly differ from those obtained with the HMM. Thus for this kind of analysis the method of setting a 50% threshold appears justified.
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    URL: http://dx.doi.org/10.1007/BF00374789
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    Oxygen consumption of oestradiol-treated rats (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 351-353 
    Details
    ISSN: 1432-2013
    Keywords: Rat ; Brown adipose tissue ; Noradrenaline responsiveness ; Oxygen consumption ; Cold acclimation ; Body temperature ; Oxidative capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rectal temperature and oxygen consumption (üüO2) were monitored in female rats acclimated either to cold or to thermoneutrality and with and without chronic administration of oestradiol. The hormone is known to inactivate brown adipose tissue (BAT) and to reduce its response to noradrenaline (NA). The role of sympathetic control was studied by administering NA or the adrenergic blocker propranolol. Oestradiol treatment did not affect rectal temperature in the states of acclimation to thermoneutrality and to cold, nor did it change the hypothermic response of cold-exposed rats to temporary food deprivation. In the cold-acclimated rats, both controls and oestradiol-treated animals exhibited similar degrees of metabolic reduction after propranolol administration in the cold and similar degrees of metabolic activation by NA at thermoneutrality. Rats acclimated to thermoneutrality showed a larger metabolic response to NA when treated with oestradiol. The results suggest that oestradiol, while inactivating the BAT response to NA, activates the NA responsiveness of other metabolically active tissues in cold-induced thermogenesis. The observation of a greater oxidative capacity in the kidney and the rectus abdominis muscle of oestradiol-treated, cold-acclimated rats would be in line with this proposal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374793
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    Alterations in the ontogeny of rat pup ultrasonic vocalization produced by prenatal exposure to nitrogen dioxide (1994)
    Springer
    Psychopharmacology 116 (1994), S. 423-427 
    Details
    ISSN: 1432-2072
    Keywords: Nitrogen dioxide ; Prenatal exposure ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to NO2 (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247472
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    Sex-dimorphic psychomotor activation after perinatal exposure to (−)-Δ9-tetrahydrocannabinol. An ontogenic study in wistar rats (1994)
    Springer
    Psychopharmacology 116 (1994), S. 414-422 
    Details
    ISSN: 1432-2072
    Keywords: Rat ; Development ; Δ-9-Tetrahydrocannabinol ; Motor behavior ; Locomotor activity ; Grooming ; Corticosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to Δ9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone. These results confirm our previous finding of a sex-dimorphic behavioral response to perinatal exposure to hashish extracts, and they suggest a role of THC-induced PA activation in the mediation of these actions.
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    URL: http://dx.doi.org/10.1007/BF02247471
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    Ontogeny of behavioral sensitization in the rat: effects of direct and indirect dopamine agonists (1994)
    Springer
    Psychopharmacology 116 (1994), S. 483-490 
    Details
    ISSN: 1432-2072
    Keywords: Behavioral sensitization ; amphetamine ; NPA ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, the abilities of NPA (a direct DA receptor agonist) and amphetamine (an indirect DA receptor agonist) to induce short- and long-term behavioral sensitization were assessed in 11- and 17-day-old rats (age at initial injection). Rats were injected on 4 consecutive days with amphetamine (1.0, 2.5, or 5.0 mg/kg), NPA (1.0 mg/kg), or saline. A final test day occurred either 2 days (experiment 1) or 8 days (experiment 2) later. On the test day, rats given successive agonist injections received a single injection of the same agonist again; whereas rats given successive saline injections received either amphetamine or NPA for the first time. Five minutes after injection, locomotor activity (line-crosses), stereotyped sniffing, and vertical activity were measured during a 30-min testing session. The results showed that 11- and 17-day-old rats exhibited behavioral sensitization when tested with NPA or amphetamine after a 2-day interval. In contrast, neither NPA nor amphetamine was able to sensitize the behaviors of preweanling rats when measured 8 days after initial drug treatments. Therefore, these results show that both direct and indirect DA agonists are able to induce short-term behavioral sensitization in preweanling rats, but that the mechanisms responsible for mediating long-term behavioral sensitization have not yet matured.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247482
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  • 148
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    Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam (1994)
    Springer
    Psychopharmacology 116 (1994), S. 475-482 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Anxiety ; Rat ; Metabolism ; Energy expenditure ; Energy substrate utilisation ; Respiratory quotient ; Midazolam ; FG-7142 ; RO 15-1788 ; Panic ; Hyperventilation ; Sympathetic nervous system ; Benzodiazepine ; Conditioned stimulus ; Respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ=CO2 produced/O2 consumed) and energy expenditure [EE=O2 consumed (364+113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 × 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with footshock (20 × 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247481
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  • 149
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    Kavapyrone enriched extract fromPiper methysticum as modulator of the GABA binding site in different regions of rat brain (1994)
    Springer
    Psychopharmacology 116 (1994), S. 469-474 
    Details
    ISSN: 1432-2072
    Keywords: Kavapyrone ; Piper methysticum ; GABA ; Rat ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plantPiper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 µM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 µM the order of enhancement in Bmax was HIP=AMY〉MED〉FC〉CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247480
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  • 150
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    Excitatory amino acid receptors in the rostral ventrolateral medulla mediate hypertension induced by carotid body chemoreceptor stimulation (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 549-554 
    Details
    ISSN: 1432-1912
    Keywords: Kynurenate ; Excitatory amino acid receptor ; Vasopressin ; Chemoreceptor ; Vasopressin antagonist ; Rostral ventrolateral medulla ; Carotid body ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The rostral ventrolateral medulla (RVLM) is involved in the mediation of cardiovascular responses to peripheral chemoreceptor stimulation. To investigate whether excitatory amino acid inputs in the RVLM are related to the responses to chemoreceptor stimulation, we microinjected kynurenate, an amino acid antagonist, unilaterally into the RVLM and examined its effects on the pressor response to stimulation of carotid body chemoreceptors. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The carotid chemoreceptors were stimulated with isotonic solutions of inorganic phosphate solution. Stimulation of carotid body chemoreceptors produced increases in blood pressure. Kynurenate injected ipsilaterally but not contralaterally into the RVLM markedly inhibited the pressor response to chemoreceptor stimulation. In rats with spinal transection, stimulation of carotid body chemoreceptors also produced increases in blood pressure. The pressor response in rats with spinal transection was inhibited by intravenous injection of a vasopressin antagonist or by kynurenate injected ipsilaterally into the RVLM. Kynurenate injected into the RVLM inhibited the pressor response to NMDA, AMPA and kainate but not to acetylcholine in intact rats. These findings indicate that excitatory amino acid receptors are involved in mediating the pressor response to carotid body chemoreceptor stimulation in the rat RVLM. It appears that the chemoreceptor stimulation produces an increase in vasopressin release and the enhancement of vasopressin release is also mediated by an increase in excitatory amino acid inputs in the RVLM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01258457
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  • 151
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    Halothane anesthesia enhances the effect of dopamine uptake inhibition on interstitial levels of striatal dopamine (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 239-244 
    Details
    ISSN: 1432-1912
    Keywords: Halothane ; Vanoxerine ; GBR 12909 ; d-Amphetamine ; Dopamine uptake ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The anesthetic, isoflurane, has been shown to potentiate the ability of the dopamine (DA)-uptake inhibitor, nomifensine, to increase the brain interstitial dopamine level ([DA]e). Since the effect of the more commenly used anesthetic, halothane, on this system is unknown, we determined [DA]e by microdialysis in the striatum of rats, conscious or anesthetized with halothane, in the presence of the more selective DA uptake inhibitor, vanoxerine (GBR 12909), or the DA releaser, d-amphetamine. Basal [DA]e was not changed by halothane. However, in halothane-anesthetized rats, the vanoxerine (3 mg/kg i.v.)-induced DA response increased severalfold compared to the response in conscious rats. The initial peak response to d-amphetamine (1 mg/kg i.v.) did not change, but the late response (1–3 h after injection) was augmented in anesthetized rats. Halothane is believed to increase firing of DA neurons in the substantia nigra and, hence, to release striatal DA. We hypothesize that [DA]e, is maintained at a normal level during the increased firing by equally increased activity of the DA transporter. However, when the DA transporter is blocked by vanoxerine, the increased DA release is unimpaired and [DA]e rises.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175028
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  • 152
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    Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 393-397 
    Details
    ISSN: 1432-1912
    Keywords: Seizures ; Development ; Rat ; Benzodiazepine ; Inverse agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An inverse benzodiazepine receptor agonist Ro 19-4603, administered intraperitoneally, was found to induce two types of motor seizures, i.e. minimal, predominantly clonic and major, generalized tonic-clonic, in rats at all developmental stages studied (7, 12, 18 and 25 days old). The developmental profile of the two types of seizure was different. Minimal seizures could be induced easily in the two youngest groups, whereas there were no marked differences in the induction of major seizures between the age groups. A lethal outcome was more common in 18- and 25-day-old rats than in younger animals. The convulsant action of the benzodiazepine agonist/inverse agonist Ro 19-4603 shows only quantitative changes during post-natal development in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00178957
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  • 153
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    The AMPA antagonists NBQX and GYKI 52466 do not counteract neuroleptic-induced catalepsy (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 61-65 
    Details
    ISSN: 1432-1912
    Keywords: AMPA receptor ; NBQX ; GYKI 52466 ; Dizocilpine ; Quinpirole ; l-DOPA ; Catalepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The AMPA antagonists NBQX (2.5, 5, 10 mg/kg) and GYKI 52466 (4.8, 8 mg/kg) were investigated in haloperidol (0.5 mg/kg)-induced catalepsy in the rat. The effects of AMPA antagonists administered either alone or in combination with the noncompetitive NMDA antagonist dizocilpine (0.02 mg/kg), with the dopamine D-2 agonist quinpirole (1 mg/kg) or with L-DOPA (50, 100 mg/kg plus benserazide) were tested. NBQX or GYKI 52466 did not exert anticataleptic effects, neither alone nor in combination with dizocilpine, quinpirole or l-DOPA. Thus, in the rat inhibition of AMPA receptors with NBQX or GYKI 52466 does not have effects predictive for an antiparkinsonian potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00178207
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  • 154
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    Expression of the α-subunit of glycoprotein hormones in the pars tuberalis-specific glandular cells in rat, mouse and guinea-pig (1994)
    Springer
    Cell & tissue research 278 (1994), S. 617-624 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Pituitary ; Pars tuberalis ; α-Subunit ; Immunocytochemistry ; In situ hybridization ; Rat ; Mouse ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The nature of the hormone(s) secreted by the pars tuberalis (PT) is still unknown. This pituitary lobe is mainly formed by specific glandular cells that differ in their ultrastructural features from the other adenohypophysial cell types. Data from the literature indicate the presence of thyroid-stimulating hormone immunoreactivity in the PT-specific cells of the rat and the Djungarian hamster but not of other species, including the mouse and guinea-pig. The PT also encloses variable numbers of pars distalis cells, essentially gonadotrophs that are mainly dispersed in its caudal area. We studied the expression of the glycoprotein hormone α-subunit in the PT of the rat, mouse and guinea-pig by in situ hybridization and immunocytochemistry. In situ hybridization, using an oligonucleotide probe complementary to rat cDNA sequence 196–237 revealed the expression of the α-subunit gene throughout the PT of the rat and the mouse; in the guinea-pig, the probe labelled no pituitary cells. Light- and electron-microscopic immunocytochemistry demonstrated α-subunit immunoreactivity in the secretory granules of the PT-specific cells in the three species examined. These cells did not react with a specific antibody against the β-subunit of luteinizing hormone, an antibody that labelled scattered gonadotrophs. The present data suggest that hormone(s) produced by the PT-specific glandular cells are, at least partly, related to glycoprotein hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050253
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  • 155
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    Expression of the α-subunit of glycoprotein hormones in the pars tuberalis-specific glandular cells in rat, mouse and guinea-pig (1994)
    Springer
    Cell & tissue research 278 (1994), S. 617-624 
    Details
    ISSN: 1432-0878
    Keywords: Pituitary ; Pars tuberalis ; α-Subunit ; Immunocytochemistry ; In situ hybridization ; Rat ; Mouse ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The nature of the hormone(s) secreted by the pars tuberalis (PT) is still unknown. This pituitary lobe is mainly formed by specific glandular cells that differ in their ultrastructural features from the other adenohypophysial cell types. Data from the literature indicate the presence of thyroid-stimulating hormone immunoreactivity in the PT-specific cells of the rat and the Djungarian hamster but not of other species, including the mouse and guinea-pig. The PT also encloses variable numbers of pars distalis cells, essentially gonadotrophs that are mainly dispersed in its caudal area. We studied the expression of the glycoprotein hormone α-subunit in the PT of the rat, mouse and guinea-pig by in situ hybridization and immunocytochemistry. In situ hybridization, using an oligonucleotide probe complementary to rat cDNA sequence 196–237 revealed the expression of the α-subunit gene throughout the PT of the rat and the mouse; in the guinea-pig, the probe labelled no pituitary cells. Light-and electron-microscopic immunocytochemistry demonstrated α-subunit immunoreactivity in the secretory granules of the PT-specific cells in the three species examined. These cells did not react with a specific antibody against the β-subunit of luteinizing hormone, an antibody that labelled scattered gonadotrops. The present data suggest that hormone(s) produced by the PT-specific glandular cells are, at least partly, related to glycoprotein hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00331382
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  • 156
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    The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat (1994)
    Springer
    Cell & tissue research 278 (1994), S. 363-378 
    Details
    ISSN: 1432-0878
    Keywords: Key words: snRNPs ; Testis ; Spermatocytes ; Spermatids ; Immunocytochemistry ; Chromatoid body ; Intermitochondrial nuage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The objective of this study was to determine the cellular and subcellular distribution of small nuclear ribonucleoprotein particles (snRNPs) in the adult rat testis in relation to the different cell types at the various stages of the cycle of the seminiferous epithelium. The distribution of snRNPs in the nucleus and cytoplasm of germ cells was quantitated in an attempt to correlate RNA processing with morphological and functional changes occurring during the development of these cells. Light-microscopic immunoperoxidase staining of rat testes with polyclonal anti-Sm and monoclonal anti-Y12 antibodies localized spliceosome snRNPs in the nuclei and cytoplasm of germ cells up to step 10 spermatids. Nuclear staining was intense in Sertoli cells, spermatogonia, spermatocytes, and in the early steps of round spermatid development. Although comparatively weaker, cytoplasmic staining for snRNPs was strongest in mid and late pachytene spermatocytes and early round spermatids. Quantitative electron-microscopic immunogold labeling of Lowicryl embedded testicular sections confirmed the light-microscopic observations but additionally showed that the snRNP content peaked in the cytoplasm of mid-pachytene spermatocytes and in the nuclei of late pachytene spermatocytes. The immunogold label tended to aggregate into distinct loci over the nuclear chromatin. The chromatoid body of spermatids and spermatocytes and the finely granular material in the interstices of mitochondrial aggregates of spermatocytes were found to be additional sites of snRNP localization and were intensely labeled. This colocalization suggests that these dense cytoplasmic structures may be functionally related. Anti-U1 snRNP antibodies applied to frozen sections showed the same LM localization pattern as spliceosome snRNPs. Anti-U3 snRNP antibodies applied to frozen sections stained nucleoli of germ cells where pre-rRNA is spliced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00414179
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  • 157
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    Selective association of nerve fibres immunoreactive for substance P or bombesin with putative cholinergic neurons of the male rat major pelvic ganglion (1994)
    Springer
    Cell & tissue research 278 (1994), S. 589-594 
    Details
    ISSN: 1432-0878
    Keywords: Autonomic ganglia ; Neuropeptides ; Pelvic plexus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The male rat major pelvic ganglion contains both sympathetic and parasympathetic neurons that supply the lower urinary and digestive tracts, and the reproductive organs. The aim of this study was to describe the distribution and identify potential targets of sensory and intestinofugal axons in this ganglion. Two putative markers of these projections were chosen, substance P for primary sensory axons and bombesin for myenteric intestinofugal projections. Varicose substance P-immunoreactive axons were associated only with non-noradrenergic (putative cholinergic) somata, and most commonly with those that contained vasoactive intestinal peptide. Immunoreactivity for substance P was also present in a small group of non-noradrenergic somata, many of which were immunoreactive for enkephalins, neuropeptide Y or vasoactive intestinal peptide. Bombesin immunoreactivity was found only in preterminal and terminal (varicose) axons, the latter of which were exclusively associated with non-noradrenergic somata that contain neuropeptide Y-immunoreactivity. Some varicose axons containing either substance P-or bombesin-immunoreactivity were intermingled with clumps of small, intensely fluorescent cells. These studies indicate that substance P-and bombesin-immunoreactive axons are likely to connect with numerically small, but discrete, populations of pelvic neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00331378
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  • 158
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    Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study (1994)
    Springer
    Cell & tissue research 278 (1994), S. 21-28 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Adrenal cortex ; Renin-angiotensin system ; Steroidogenesis ; Electron microscopy ; Morphometry ; Rat ; transgenic (mRen2) 27
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305774
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  • 159
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    The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat (1994)
    Springer
    Cell & tissue research 278 (1994), S. 363-378 
    Details
    ISSN: 1432-0878
    Keywords: snRNPs ; Testis ; Spermatocytes ; Spermatids ; Immunocytochemistry ; Chromatoid body ; Intermitochondrial nuage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The objective of this study was to determine the cellular and subcellular distribution of small nuclear ribonucleoprotein particles (snRNPs) in the adult rat testis in relation to the different cell types at the various stages of the cycle of the seminiferous epithelium. The distribution of snRNPs in the nucleus and cytoplasm of germ cells was quantitated in an attempt to correlate RNA processing with morphological and functional changes occurring during the development of these cells. Light-microscopic immunoperoxidase staining of rat testes with polyclonal anti-Sm and monoclonal anti-Y12 antibodies localized spliceosome snRNPs in the nuclei and cytoplasm of germ cells up to step 10 spermatids. Nuclear staining was intense in Sertoli cells, spermatogonia, spermatocytes, and in the early steps of round spermatid development. Although comparatively weaker, cytoplasmic staining for snRNPs was strongest in mid and late pachytene spermatocytes and early round spermatids. Quantitative electron-microscopic immunogold labeling of Lowicryl embedded testicular sections confirmed the light-microscopic observations but additionally showed that the snRNP content peaked in the cytoplasm of midpachytene spermatocytes and in the nuclei of late pachytene spermatocytes. The immunogold label tended to aggregate into distinct loci over the nuclear chromatin. The chromatoid body of spermatids and spermatocytes and the finely granular material in the interstices of mitochondrial aggregates of spermatocytes were found to be additional sites of snRNP localization and were intensely labeled. This colocalization suggests that these dense cytoplasmic structures may be functionally related. Anti-U1 snRNP antibodies applied to frozen sections showed the same LM localization pattern as spliceosome snRNPs. Anti-U3 snRNP antibodies applied to frozen sections stained nucleoli of germ cells where pre-rRNA is spliced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00414179
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  • 160
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    Changes in fibre-type composition and myosin heavy-chain IId isoform in rat soleus muscle during recovery period after hindlimb suspension (1994)
    Springer
    European journal of applied physiology 68 (1994), S. 102-106 
    Details
    ISSN: 1439-6327
    Keywords: Hindlimb suspension ; Recovery ; Soleus muscle ; Fibre-type composition ; Myosin heavy-chain IId isoform ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the changes in myosin heavy-chain (HC) isoforms and fibre-type composition in rat soleus muscle using both myosin adenosine triphosphatase staining and sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) analyses during the recovery period after 4 weeks of hindlimb suspension. Although there was no change in type IIc fibres after the suspension, an increase in this type of fibres was observed during the 1- to 4-week recovery period. The increase in type Ilc fibres was considered to be due to a shift from type Ila to IIc fibres. The SDS-PAGE analysis revealed the presence of the HC IId isoform, which was not observed in the control muscle, after a 4-week hindlimb suspension. The HC IId isoform gradually decreased over 3 weeks of recovery and disappeared in the 4th week of recovery after the suspension. These results suggest that the hypogravity conditions induced by hindlimb suspension stimulated the synthesis of the HC IId isoform, whereas an increase in mechanical load to the muscle accelerated the degradation of the HC IId isoform and the synthesis of type Ilc fibres during the recovery period after hindlimb suspension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00599249
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  • 161
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    Muscle glycogen repletion and pre-exercise glycogen content: effect of carbohydrate loading in rats previously fed a high fat diet (1994)
    Springer
    European journal of applied physiology 68 (1994), S. 483-488 
    Details
    ISSN: 1439-6327
    Keywords: Carbohydrate loading ; Glycogen utilization ; Glycogen repletion ; Glycogen synthase ; Muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently reported that rates of muscle glycogen repletion during the early period of recovery were increased by carbohydrate (CHO) loading in rats previously fed a high fat diet. However, the reason for this remained unanswered. The purpose of this study was to examine whether an increase of glycogen utilization due to an elevated pre-exercise glycogen store would enhance rates of glycogen repletion in muscle. Despite an equal degree of glycogen depletion, the rates of glycogen repletion of soleus, red and white gastrocnemius muscles by postexercise administration of glucose (3.0 g · kg−1 body mass) and citrate (0.5 g · kg−1 body mass) were faster in the CHO loaded (3 days) rats than in the nonloaded rats, as a result of elevated pre-exercise glycogen content and consequently the greater glycogen utilization. The higher rate of muscle glycogen repletion may in part be explained by increased postexercise glycogen synthase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00599517
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  • 162
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    Protein synthesis in the hippocampal slice: Transient inhibition by glutamate and lasting inhibition by ischemia (1994)
    Springer
    Metabolic brain disease 9 (1994), S. 235-247 
    Details
    ISSN: 1573-7365
    Keywords: Hippocampus ; Slices ; Protein synthesis ; Ischemia ; Glutamate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Protein synthesis was measured in hippocampal slices which were exposed to glutamate (1 mM or 10 mM) or which were deprived of glucose and oxygen (‘in vitro ischemia’) for 15 min. Glutamate at 1 mM, a concentration estimated to occur duringin vivo ischemia did not affect protein synthesis. Ten mM glutamate inhibited protein synthesis immediately after exposure (50% of control values) and reduced ATP levels to about 30% of the control. After two hours, slices fully recovered their protein synthesis and energy metabolism. The effect of 10 mM glutamate was not receptor-mediated, as NMDA, AMPA, or metabotropic receptor antagonists failed to block the glutamate effect. Immediately after ischemia, protein synthesis was reduced to 30% of control values, and 2 hours later it was still depressed to one-half of control values. Energy charge, however, recovered completely. Ischemic inhibition of protein synthesis was not reversed by glutamate receptor antagonists. The data indicate that inhibition of protein synthesis in hippocampal slices during ischemia is not glutamate-dependent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01991197
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  • 163
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    Experimental oxygen-induced retinal detachment in the newborn Wistar rat (1994)
    Springer
    Documenta ophthalmologica 87 (1994), S. 315-329 
    Details
    ISSN: 1573-2622
    Keywords: Experimental retinal detachment ; Glial fibrillary acidic protein ; Müller cells ; Oxygen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted an extensive histological study of the retinas of newborn rats that had been exposed to hyperoxic conditions. Our aim was to verify whether it is possible, using oxygen alone, to induce retinal detachment, a lesion that is characteristic of the more advanced stages of retinopathy of prematurity (ROP). Eight litters (total number of animals: 64) of newborn, albino Wistar rats were used. Four litters (32 rats) were exposed to 80% oxygen for the first ten days of life. Some of these rats were then removed to room-air environments where they were kept for two, three or four more weeks. The other four litters (32 rats) were maintained for the entire period in room-air. On the 11th, 25th, 32nd and 39th days of life rats from both the exposed and control groups were sacrificed and 5 micron sections of their in toto eyeballs were submitted to histological evaluation and immunohistochemical studies. Folding of the internal retinal layers was observed in some of the animals exposed to hyperoxia, as well as those kept in room air. These folds did not alter the overall thickness of the retina itself and were probably congenital. Retinal folds and microdetachments were seen in many of the retinas from the exposed group of rats. Extensive detachment was observed in one of the rats sacrificed after two weeks of room-air recovery, in two of those recovered for three weeks and in two exposed to four weeks of room air. The sections containing these areas of retinal detachment showed marked increases in glial fibrillary acidic protein (GFAP) in immunocytochemical studies, suggesting that Müller cells might play a role in the pathogenesis of retinal detachment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01203341
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  • 164
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    Microvascular transfers of serratus anterior muscles in rats (1994)
    Springer
    European journal of plastic surgery 17 (1994), S. 1-4 
    Details
    ISSN: 1435-0130
    Keywords: Rat ; Free flaps ; Serratus anterior ; Microvascular surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The serratus anterior muscle in the rat is supplied by the serratus division of thoracodorsal vessels, in a pattern similar to man [2]. The serratus anterior muscles were transferred to the groin area as a free muscle flap in 17 rats and as a free muscle graft in 13 rats. In the free muscle flap group, the serratus anterior muscles of 8 of 10 rats survived; histological examination showed them to be viable and the vascular anastomoses were patent at the 30th day. In the free muscle graft group, all of the muscle grafts became necrotic. As a result, it is concluded that the microvascular transfer of serratus anterior muscles in rats is a useful small animal model for microsurgical laboratory training of clinical free flap transfers and also for performing pharmacological and biochemical studies in transplanted muscle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176491
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  • 165
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    Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 59-69 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: β-Nitrostyrene derivatives of adenosine 5′-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3, 4, and 5 atoms to give compounds of the benzyl, oxyethyl, oxypropyl, and oxybutyl series, respectively (Schemes 1 and 2). Adenosine 5′-esters were prepared in the benzyl and oxypropyl series only. Compared to the compounds in the parent series without spacer (IC50 = 0.7-12 μM), most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (IC50 ≥ 100 μM). The only exceptions were the free acids 19 and 20 with IC50 values of ca. 5 μM. It is noteworthy that esterification of these two hydrogen glutarates with either MeOH or adenosine yielded inactive compounds, which is in contrast to the corresponding substances without spacers.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/hlca.19940770109
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  • 166
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    Synthese und Eigenschaften der Furo- und Thieno-Analogen von PQQ-TriesterTeil einer Präsentation am ‘2nd International Symposium on PQQ and Quinoproteins’, 19.-22. Nov. 1991, Yamaguchi, Japan. (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 100-110 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis and Characterization of the Furo and Thieno Analogues of the Triester of PQQWe report here the synthesis and properties of the furo and thieno analogues of 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9- tricarboxylic acid ( = PQQ), i.e. the furo- and thieno[2,3-f]quinoline-4,5-quinone (FQQ and TQQ, resp.) derivatives B and C, obtained as triesters. The triester of PQQ derivative A is much more stable than the triesters of B or C, and only the triester of A shows strong activity in nonenzymatic catalytic oxidations.
    Additional Material: 1 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19940770113
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  • 167
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    Computational Approach to the Receptor-Bound Conformation of Cyclosporin A (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 171-181 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The conversion of the conformation of cyclosporin A (CsA) observed in CHCl3 to the receptor-bound state is investigated by two molecular-mechanics methods, template forcing and dynamic forcing. The conformations of CsA in CHCl3 and complexed with LiCl in THF as determined by NMR are used as starting structures. The transition starting from the CsA/CHCl3-derived conformation is hindered by steric interactions of two side chains (MeBmt1 and Val5). While starting with the CsA/LiCl-derived conformation, the conversion is facile. It is illustrated that these calculations, which are of artificial character, using only the starting and final structures of the observed conformational transition during the receptor-binding event, allow an insight into the interactions between the substrates and receptor in terms of an induced fit.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770120
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  • 168
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    Electrochemical Study of Phase-Transfer Catalysis Reactions: The Williamson ether synthesis (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 231-242 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The transfer properties of the ionic species involved in the Williamson ether synthesis by phase-transfer catalysis were investigated using electrochemical techniques developed for the study of polarised liquid/liquid interfaces. This approach allows the measurement of the apparent partition coefficients of the transferring species. From these data, it is proposed that the role of the phase-transfer catalyst salt in the reaction mechanism is to establish a Galvani distribution potential difference between the two phases which in turn acts as the driving force for transferring the reactive aqueous ions to the organic phase.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770125
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  • 169
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    Synthesis of (R)- and (S)-5-(Hydroxymethyl)-3-isopropyloxazolidin-2-one, intermediates in the preparation of optically active β-blockers (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 252-256 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The (R)- and (S)-5-(hydroxymethyl)-3-isopropyloxazolidin-2-ones, ((R)- and (S)-2, resp.), pivotal intermediates in the preparation of optically active β-blockers, were synthesized using (R,E)-2-hydroxypent-3-enenitrile (1) as the chiral starting material. In the synthesis of (R)-2, a known cyclization/inversion step was applied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770127
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  • 170
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    Calorimetric Measurements of the Complexation of Cyclosporin A, Ascomycin, Fujimycin, and Rapamycin with Lithium Chloride and with an Immunophilin (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 291-305 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Solutions (2 ml) of small linear and cyclic peptides (4-11), of a peptolide containing nine amino acids and a lactate moiety (12), of the cyclic undecapeptide cyclosporin A (CS, 1), and of the macrolides ascomycin, fujimycin, and rapamycin (13-15) in THF were added to excess LiCl, LiBr, or LiClO4 (up to 3000 equiv. in 40 ml THF) in a calorimeter (calorimetric titration). The enthalpies of interaction measured are in the range of ΔH = -8 to -37 kcal/mol. A similar experiment was carried out with one of the binding proteins of cyclosporin, the human cyclophilin A, to give the thermodynamic parameters for the complexation ΔH = -16, ΔG° = -10 kcal/mol, and ΔS° = -20 cal/mol·deg. at 25° which corresponds to an equilibrium constant K = 2·107 l/mol, in good agreement with the result of independent measurements using different methods. NMR Measurements of the macrolides in (D8)THF containing LiCl show strong down-field shifts of signals of the H-atoms next to C=O and C-OH groups in these molecules.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770129
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  • 171
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    NMR of Terminal Oxygen. Part 13Part 12: [1].. 17O-NMR spectra of C-nitroso compounds, thionitrites and NO+ Ion: Resonance effects in O=N - X compounds and correlation with CD spectra (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 306-316 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 17O-NMR signals of four true C-nitroso compounds 1-4 appear at particularly low field (1550-1265 ppm), whereas the dimers (azodioxy type) resonate at ca. 400 ppm and the ‘isonitroso compounds’ ( = quinone-oximes; 5 and 6) at ca. 250 ppm. S-Nitroso compounds ( = thionitrites; 8 and 9) show shift values of ca. 1300 ppm, not far from C - NO; the NO+ ion is much stronger shielded (474 ppm). The results, together with those for higher-shielded nitroso compounds X - NO (X = RO, R2N, Cl, O-) are discussed in terms of (a) resonance stabilization through n-donation from X(π-bond order, approximated by the known barriers of rotation around the X - N bond) and of (b) electronic excitation energies ΔE. The latter are approximated by long-wave (symmetry-forbidden) UV/VIS absorptions and confirmed, where available, by the maxima of the curves of circular dichroism (CD); the CD curve of thionitrite 9 has been measured. It is found that the δ(17O) values of X - NO depend both on bond order and on ΔE, which could not be separated. The higher shielding of NO+ compared with X - N=O is explained on the basis of anisotropy effects, which differ between sp and sp2 systems.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770130
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  • 172
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    Masthead (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994) 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770101
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  • 173
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    Enantioselective synthesis of (-)-conduramine C1 and aminobromocyclitol derivatives‘Naked Sugars’ as Synthetic Intermediates, Part XXV. Part XXIV, see [1a]; Part XXIII, see [1b]. (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1-9 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (1S,2R,6R,7R)-4-Phenyl-3,10-dioxa-5-azatricyclo[5.2.1.02,6]dec-4-en-9-one ((+)-5) obtained in 6 steps from the Diels-Alder adduct of furan to 1-cyanovinyl (1S)-camphanate ((+)-3) was reduced to the corresponding endo-alcohol (-)-6 the treatment of which with HBr/AcOH provided (-)-(3aS,4S,6R,7S,7aR)-4β-bromo-3aβ,4,5,6,7,7aβ-hexahydro-2-phenyl-1,3-benzoxazole-6β,7α-diyl diacetate ((-)-17). Elimination of HBr with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and acidic hydrolysis furnished (-)-(1R,2S,3R,4R)-4-aminocyclohex-5-ene-1,2,3-triol ( = (-)-conduramine C1;(-)-1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770103
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  • 174
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    Nucleotides Part XLPart XXXIX: [1].. Synthesis and Characterization of Modified 2′-5′ Adenylate Trimers-Potential Antiviral Agents (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 10-22 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2′-5′ Adenylate trimers 41-44 carrying the (tert-butyl)dimethylsilyl (tbds) group at the 3′-OH position of various sugar moieties were synthesized via the phosphoramidite method. The use of the (tert-butyloxy)carbonyl (boc) and 2-(4-nitrophenyl)ethylsulfonyl (npes) groups for 2′-OH protection in neighbourhood to the 3′-O-tbds residue was compared during the synthesis of the target trimers. For other functional positions, the use of the 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) blocking groups were favoured.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/hlca.19940770104
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  • 175
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    Metal complexes of macrocyclic ligands. Part XXXVIIPart XXXVI: [1].. Synthesis of Heteroditopic Bis-macrocycles and Their Potential for Preparing Heterobinuclear Metal Complexes (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 23-35 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new and generally applicable synthetic path for the preparation of heteroditopic bis-macrocycles using tri-N-protected tetraazacycloalkanes as building blocks and bromoacetyl bromide as bridging reagent is described. In the first step, bromoacetyl bromide is used as acylating agent for one of the macrocycles, whereas in the second step it is used as alkylating agent for the second macrocycle, thus giving protected bis-macrocyclic amides (e.g. 6). After reduction of the amide moiety and deprotection, bis-azamacrocycles with an ethylene bridge are obtained (e.g. 8). The corresponding homoditopic bis-macrocycles 16 and 17 are also prepared for comparison purpose. Spectrophotometric studies indicate that bis-macrocycle 8, which consists of a 12- and a 14-membered ring, binds two metal ions with equal affinity, whereas compound 13, in which an unsubstituted (cyclam) and a trimethyl-substituted tetraazacyclotetradecane unit (Me3cyclam) are bridged, shows selective metal-ion binding. The first metal ion is always incorporated into the cyclam unit, whereas the second one binds to the Me3cyclam macrocycle. Thus, by sequential addition of two different metal ions, heterobinuclear complexes can easily be prepared. The electrochemistry of the binuclear Ni2+ complexes, studied by CV and DPV, as well as the EPR spectra of the binuclear Cu2+ complexes clearly indicate metal-metal interactions.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770105
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  • 176
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    Thermoconversion of Caryophyllene- to Farnesene-Type Sesquiterpenes. Short access to the enantiomers of (6RS,7RS)- and (6RS,7SR)-6,7-epoxy-6,7-dihydro-β-farnesenes (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 36-40 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Flash-vacuum thermolysis of the four diastereoisomeric 5,6-epoxy-5,6-dihydro-caryophyllenes 1-4 at 500-550°/0.1-0.7 Torr leads to the hitherto unreported enantiomers of (6RS,7RS)- and (6RS,7SR)-6,7-epoxy-6,7-dihydro-β-farnesenes ((±)-5 and (±)-6, resp.). In particular, (+)-5 is formed in 45% yield (ca. 90% ee) and is, thus, an attractive chiral building block for natural-product synthesis.
    Additional Material: 2 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19940770106
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  • 177
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    Oceanapins A-F, Unique Branched Ceramides Isolated from the Haplosclerid Sponge Oceanapia cf. tenuis of the Coral SeaDedicated to the memory of Margherita Ratti (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 51-58 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of ceramides, called oceanapins A-F (2-7), which are unique for branching at both the sphingosine and fatty-acid chains, have been isolated as pure compounds from the haplosclerid sponge Oceanapia cf. tenuis of the Coral Sea. Following acid hydrolysis, both the fatty-acid and the sphingosine portions were obtained separately, which allowed their unequivocal structural definition. The absolute configuration was secured via protection of C(1′)-OH and Mosher's esterification at C(3′)-OH of the oceanapins.
    Additional Material: 1 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19940770108
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  • 178
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    Single-Crystal Structure of the Solvent-Separated Radical Ion Pair [9,10-diphenylanthracene.⊖][Na⊕(THF)6] and its implication for cation solvationDedicated to Peter Weyerstahl on the occasion of his 60th birthdayPart 26 of ‘Structures of Charge-Perturbed or Sterically Overcrowded Molecules’; Part 25: [1]. (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 41-50 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The one-electron transfer to large π-delocalized hydrocarbons provides an interesting possibility to crystallize solvent-separated ion-pair salts containing optimally solvated cations. Accordingly, the reduction of 9,10-diphenylanthracene in aprotic THF solution at a sodium metal mirror allows to grow dark-blue prismatic crystals of its radical anion and sixfold THF-solvated sodium cation. The structure of the radical anion is very similar to that recently published for the neutral molecule. According to AM1 hypersurface calculations based on the structural data, the phenyl twist angles obviously must be determined by lattice packing, and the negative charge is delocalized predominantly within the anthracene π system. The counter cation [Na⊕(THF)6], reported ordered for the first time, shows nearly octahedral coordination within a rather densily packed solvent shell. Due to the strong repulsions between the solvent molecules, its isodesmically calculated solvation enthalpy is smaller than that of the analogous dimethoxyethane complex [Na⊕(DME)3].
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/hlca.19940770107
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  • 179
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    Radical Cations of Tetrazinodi(heteroarenes): An ESR and ENDOR Study (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 86-91 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 14N- and 1H-Coupling constants, determined by ESR, ENDOR, and general-TRIPLE-resonance spectroscopy, are reported for the radical cations of tetrazinodi(heteroarenes) 1-8. The results comply with the expectation that donor properties of these compounds are mainly due to the electron-rich dihydrotetrazine ring.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770111
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  • 180
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    Antiparallel β-Sheet Conformation in Cyclopeptides Containing a Pseudo-amino Acid with a biphenyl moiety (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 70-85 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The biphenyl-containing pseudo-amino acids 2′-(aminomethyl)biphenyl-2-carboxylic acid (Abc; 1) and 2′-(aminomethyl)biphenyl-2-acetic acid (Aba; 2) are used as rigid spacers in the backbone of the cyclic peptides cyclo (-Abc-Ala-Phe-Gly-)2 (5), cyclo(-Abc-Ala-Val-Gly-)2 (6), cyclo(-Aba-Gly-Phe-Ala-)2 (7), and cyclo(-Aba-Ala-Phe-Gly-)2(8). Three different interconverting diastereoisomers are found in solutions of each of these cyclopeptides due to the atropisomerism of the biphenyl units. NMR Techniques and molecular-dynamics calculations allow to conclude that the major diastereoisomer of 5 (and 6) in (D6)DMSO adopts a β-sheet conformation. It is proposed that the pseudo-amino acid 1 of (R)-chirality forms, with attached L-amino acids, a H-bonding pattern comparable to a β-turn (see D in Fig. 4 and F).
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/hlca.19940770110
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  • 181
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    Vitamin-B12-katalysierte C,C-Bindungsverknüpfung: Synthese von Jasmonaten via sequentielle Radikal-Reaktion (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 92-99 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Vitamin-B12-Catalyzed C, C-Bond Formation: Synthesis of Jasmonates via Sequential Radical ReactionThe Cbl-catalyzed electroreduction of 3-(2′-bromo-1′-ethoxyethoxy)cyclopenten (1a) in presence of 1-cyanovinyl-acetate (8) gave, in a sequential radical reaction (5-exo-trig-cyclization of 1a followed by addition to 8), 1-cyano-2-(2′-ethoxy-hexahydro-2′H-cyclopenta[b] furan-4′-yl)ethyl acetate (10a). This intermediate was transformed to methyl jasmonate (7; four steps) and epituberolide (9; three steps) in 20 and 31% yield, respectively, from cyclopent-2-en-l-ol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770112
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    Die Synthese von Azaisomeren des Triesters von PQQ: 3H-Pyrrolo[3,2-f]-, 1H-Pyrrolo[3,2-h]- und 7H-Pyrrolo[2,3-h]chinolinchinon-Derivate (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 111-120 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Synthesis of Azaisomers of the Triester of PQQ: 3H-Pyrrolo[3,2-f]-, 1H-Pyrrolo[3,2-h]-, and 7H-Pyrrolo[2,3-h]quinolinequinone DerivativesWe describe here the synthesis of the title compounds 3-5, starting from highly substituted aminoindoles. The annelated pyridine rings were built up in each case with dimethyl 4-oxoglutaconate according to Corey's procedure. All three o-quinone derivatives 3-5 are stable compounds, comparable to PQQ-triester. The azaisomers vary in biological activity from practically inactive to strong inhibition of the α-amidating enzyme or the ornithin decarboxylase.
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  • 183
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    A Novel Approach to 2,2-Disubstituted 1,2-Dihydro-4-phenylquinolines (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 608-614 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The reaction of 2-(1-phenylvinyl)aniline and 4-chloro-2-(1-phenylvinyl)aniline with acetophenone derivatives, 1-(naphthalen-1-yl)ethanone and 1-(furan-2-yl)ethanone in toluene at 110-115° with toluene-4-sulfonic acid as a catalyst leads in good-to-excellent yields to the 2,2-disubstituted 1,2-dihydro-4-phenyl-quinolines 1-18 (Scheme 1, Table). The structure of the new racemic 1,2-dihydroquinolines 1-18 is determined by NMR spectroscopy. A reaction mechanism proceeding via a 6π-electrocyclic rearrangement of 2-(1-phenylvinyl)anils 19 as the key step is proposed for the formation of these compounds (Scheme 1). The scope and limitations of the novel methods are discussed (Scheme 2).
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  • 184
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    Facile Synthesis of 2′-Deoxyisoguanosine and Related 2′,3′-Dideoxyribonucleosides (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 622-630 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 2′-deoxyisoguanosine (1) was synthesized by a two-step procedure from 2′-deoxyguanosine (5). Amination of silylated 2′-deoxyguanosine yielded 2-amino-2′-deoxyadenosine (6) which was subjected to selective deamination of the 2-NH2 group resulting in compound 1. Also 2′,3′-dideoxyisoguanosine (2) was prepared employing the photo-substitution of the 2-substituent of 2-chloro-2′,3′-dideoxyadenosine (4). The latter was synthesized by Barton deoxygenation from 2-chloro-2′-deoxyadenosine (3) or via glycosylation of 2,6-dichloropurine (12) with the lactol 13. Compound 1 was less stable at the N-glycosylic bond than 2′-deoxyguanosine (5). The dideoxynucleoside 2 was deaminated by adenosine deaminase affording 2′,3′-dideoxyxanthosine (17).
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  • 185
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    Derivatives of (2R)-N-Glyoxylbornane-10,2-sultam and Their Use as auxiliaries in the diastereoselective spirocyclization of 2-substituted tryptamines7th Communication on ‘Indoles, Indolenines, and Indolines’; 6th communication: [1]. (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 615-621 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A crude hydrate 6 and a crystalline hemiacetal 7 of glyoxylamide 4 were prepared from crotonamide 5 (Scheme 2). Particularly hemiacetal 7, but also 6 and the ‘dimer’ 8 (obtained from 7) may serve as homochiral auxiliaries. The structure of 8 was determined by X-ray analysis. By arenesulfonyl halides, tryptimines 12-14 of 4 were diastereoselectively transformed into spirotricycles 15-17 and 19.
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    URL: http://dx.doi.org/10.1002/hlca.19940770304
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  • 186
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    Synthesis and Conformational Analysis of 2′-Deoxy-2′-(3-methoxybenzamido)adenosine, a rational-designed inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH) (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 631-644 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of 2′-benzamido-2′-deoxyadenosine analogues were synthesized in an effort to find new lead structures for the treatment of sleeping sickness. The 2′-deoxy-2′-(3-methoxybenzamido)adenosine (1h) was proved to be a selective inhibitor of the parasite glyceraldehyde 3-phosphate dehydrogenase which confirms the modeling studies. The solution-state conformation of 2′-(thiophene-2-carboxamido) analogue 1d demonstrates a 2′-endo conformation, an orientation of the thiophene ring under the ribose moiety, and the base part occupying a ‘syn’/‘anti’ equilibrium.
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  • 187
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    Enantioselective Formation of Bicyclic Lactones by Rhodium-Catalyzed Intramolecular CH-insertion reactions (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 645-654 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The decomposition of cyclohexyl diazoacetate (5a) in the presence of the chiral [Rh2{(2S)-mepy}4] catalyst leads to a 3:1 cis/trans mixture of bicyclic lactone 6a with an enantiomeric excess of 95-97% (cis) and 90% (trans). The conformationally rigid tert-butyl derivatives 5b and 5c afford, in the presence of the same catalyst, 6b and 6c, respectively, via insertion into the equatorial C—H bonds exclusively, with ee's of ca. 95%. A remarkable degree of induction (92-95%) results in the lactone 6g upon decomposition of 1-isopropyl-2-methylpropyl diazoacetate (5g). The diazoacetates derived from 1-methylcyclohexanol, cyclopentanol and 1-methylcyclopentanol (5d-f) afford under similar conditions insertion products with higher diastereoselectivity, but significantly lower enantioselectivity. Other dirhodium catalysts are less efficient.
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  • 188
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    A Concise Synthesis of (E)- and (Z)-Neomanoalides (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 661-667 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The first synthesis of (Z)-neomanoalide (4) and an improved synthesis of its (E)-isomer 3 was accomplished in a concise, regiocontrolled manner by exploiting 2-[(tert-butyl)dimethylsiloxy]-4{[(tert-butyl)dimethylsiloxy]-methyl}furan (6) as the key reagent. Lithiation of 6 and subsequent reaction with the (2Z)- or (2E)-isomer of (6E)-3-{[(tert-butyl)dimethylsiloxy]methyl}-7-methyl-9-(2′,6′,6′-trimethylcyclohex-1′-enyl)nona-2,6-dienyl bromide (5), followed by hydrolysis, afforded the corresponding neomanoalide.
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    URL: http://dx.doi.org/10.1002/hlca.19940770309
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  • 189
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    Stable Quinone Methides: Regioselective para-Oxidation of a 2,4-bis[(alkylthio)methyl]phenol and addition reactions to quinonemethides (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 655-660 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 2,4-bis-functionalized phenol 1 is dehydrogenated regioselectivity with potassium ferricyanide, affording the corresponding p-quinonemethide 2. Hydrolysis of 2 affords a mixture of dithioacetal 5a and benzaldehyde 6; 1,6-addition of thiols to 2 gives the dithioacetals 5 of benzaldehyde 6; reaction of 2 with 2,2′-azobis(isobutyronitrile) (= 2,2′-dimethyl-2,2′-azobis(propanenitrile)) leads to 9a, 9b, and 10, addition products of the 1-cyano-1-methylethyl radical. The structures of all products are confirmed mainly by 1H- and 13C-NMR spectroscopy, and the mode of their formation is discussed.
    Additional Material: 2 Tab.
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  • 190
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    Oligosaccharides Related to Tumor-Associate Antigens. Part 2Part 1: [1].. Conformational analysis of the trisaccharide α-L-Fucp-(1→2)-β-D-Galp-(1→3)-β-D-GalpNAc, epitope structure recognized by the MBr1 antibody (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 668-678 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The conformational space of the trisaccharide α-L-Fuc-(1→2)-β- D-Gal-(1→3)-β -D-GalNAc-1-OPr (2) and of its component disaccharide moieties α -L-Fuc-(1→2)-β -D-Gal-1-OMe (3) and β -D-Gal-(1→3)-β- D-GalNAc-1-OPr (4) was investigated with the aid of molecular-mechanics energy minimizations and molecular-dynamics simulations. These calculations suggested the occurrence of two conformations for each compound characterized by different φ and Ψ glycosidic angles. However, 1H-NMR investigation of D2O solutions of 2-4 indicated a sure preference for one of the two conformers with a contribution of the other one ranging from negligible to low.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/hlca.19940770310
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  • 191
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    Synthesis of a New Bivalent Hirudin Analog (hirufos), which includes a stable 4′-phosphono-L-phenylalanine mimic of (L-tyrosine O4-sulfate)-63 (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 679-684 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis on solid phase of a new derivative of the anticoagulant protein hirudin is described (see Scheme and Fig.1, I). The henicosapeptide is a bivalent conjugate of the C-terminus of hirudin and of the active-site-binding tetrapeptide D-Phe-Pro-Arg-Pro linked via a tetraglycine spacer. The peptide, for which the name hirufos was coined, incorporates a stable phosphono derivative of L-phenylalanine which, combined with the other structural modifications, leads to a potent anticoagulant agent. Synthesis was readily achieved by the (9H-fluoren-9-yl)-methoxycarbonyl (Fmoc) strategy followed by acidolytic cleavage from the resin and deprotection, including the liberation of the crucial phosphonic group on L-phenylalanine.
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    URL: http://dx.doi.org/10.1002/hlca.19940770311
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  • 192
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    Organic Reactions in the Solid State: The reactivity of guest molecules in tri-o-thymotide clathrates (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 691-708 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Tri-o-thymotide (TOT) clathrates are enantiomorphous and enantioselective (chiral cages). It was shown that an external molecular reactant can diffuse into the TOT host crystal lattice and reacts with the included molecule (guest) in characteristic ways, differing from those occurring in liquid solutions. Several aspects of the action of hydrogen halides (HCl, HBr) on the chemical behavior of included oxiranes were investigated for solid-gas and solid-liquid (aqueous) systems. Under well established experimental conditions, these reactions gave regiospecifically one target product and were asymmetric. The included substrate underwent first an acid-catalyzed allylic isomerization that is cage-specific and mostly quantitative. In sheer contrast, strong basic conditions were required to promote, in reduced yield, the analogous transformation in solution. The regiospecificity and enantioselectivity of several intra-crystalline conversions allowed the accurate determination of the absolute configuration of several guest molecules. Kinetic measurements were achieved that disclosed some striking features of this new type of heterogeneous reactions. Tentative models for the cage stereoselective mechanisms are briefly discussed.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/hlca.19940770313
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  • 193
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    1:1 Metal Complexes of Bivalent Cobalt, Nickel, Copper, Zink, and Cadmium with the Tripodal Ligand tris[2-(dimethylamino)ethyl]amine: Their stabilities and the X-ray crystal structure of its copper(II) complex sulfate (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 685-690 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The complex formation by Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ with tris[2-(dimethylamino)ethyl]amine (N(CH2CH2NMe2)3, Me6tren) was investigated at 25° and at an ionic strength of 1, using VIS spectroscopy and potentiometric measurements. The stability constants of these complexes are compared with those of tris(2-aminoethyl)amine (N(CH2CH2NH2)3, tren), obtained under the same conditions. The values of the constants for Me6tren are much lower than those for tren, due to the bulky Me substituents. The values of the constants can be correlated with the ability of the individual metal ions to adopt coordination number 5. This appears to be easier for Cu2+ and Co2+ than for Cd2+ and Zn2+ and is very difficult for Ni2+. The 1:1 complexes [ML(H2O)]2+ are monoprotonic acids whose pKs values are similar or lower than those of the corresponding aquametal ions. The X-ray crystal structure of the copper(II) complex [Cu(SO4)(Me6tren)] · 8H2O reveals pentacoordination at the central ion. The UV/VIS spectra of the aqueous solutions of the Co2+, Ni2+, and Cu2+ 1:1 complexes confirm that the same coordination number is present also in these complexes.
    Additional Material: 5 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19940770312
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  • 194
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    The Revised Structure of the Norditerpenoid Alkaloid Peregrine (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1768-1772 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The structure of peregrine (1), a norditerpenoid alkaloid isolated from Delphinium peregrinum var. elongatum BOISS., was revised on the basis of the 1H-COSY, HMQC, HMBC, and ROESY NMR spectra and of the X-ray analysis of its parent alcohol 2. Some of the 13C-NMR resonances of 1 and the related alkaloids peregrine alcohol (2), 14-O-acetylperegrine (3), bicoloridine (4), bicoloridine alcohol (5), 6-O-acetylbicolorine (6), bicolorine (7), and 14-O-acetylbicolorine (8), were also reassigned.
    Additional Material: 4 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19940770708
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  • 195
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    Nucleotides. Part XLIVPart XLIII: [1].. Synthesis, characterization, and biological activity of monomeric and trimeric cordycepin-cholesterol conjugates and inhibition of HIV-1 replication (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1757-1767 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The antivirally active 3′-deoxyadenylyl-(2′-5′)-3′-deoxyadenylyl-(2′-5′)-3′-deoxyadenosine (cordycepin trimer core) was modified at the 2′- or 5′-terminus, by attachment of cholesterol via a carbonate bond (→ 15) or a succinate linker (→ 16 and 27) to improve cell permeability. The corresponding monomeric conjugates 4, 7, and 21 of cordycepin were prepared as model substances to study the applicability of the anticipated protecting groups - the monomethoxytrityl (MeOTr), the (tert-butyl)dimethylsilyl (tbds), and the β -eliminating 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) groups - for the final deblocking steps without harming the ester bonds of the conjugate trimers. The syntheses were performed in solution using phosphoramidite chemistry. The fully protected trimer conjugates 13, 14, and 26 as well as all intermediates were characterized by elemental analyses, UV and 1H-NMR spectra. The deblocked conjugates 15, 16, and 27 were pure according to HPLC and showed the correct compositions by mass spectra. Comparative biological studies indicated that cordycepincholesterol conjugate trimers 16 and 27 were 333- and 1000-fold, respectively, more potent inhibitors of HIV-1-induced syncytia formation than cordycepin trimer core.
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  • 196
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    Metal-Ion-Coordinating Properties of a Viral Inhibitor, a pyrophosphate analogue, and a herbicide metabolite, a glycinate analogue: The solution properties of the potentially five-membered chelates derived from phosphonoformic acid and (aminomethyl)phosphonic acid (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1738-1756 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The pyrophosphoric-acid-analogue phosphonoformic acid (pfa) and the amino-acid-analogue (aminomethyl)phosphonic acid (ampa) both form, in the deprotonated state, i.e., as -OOC-PO32- and H2N—CH2—PO32-, respectively, five-membered chelate rings with metal ions. pfa inhibits both phosphate transport and virus replication, while ampa is a metabolic product of the common herbicide glyphosate ( = N-(phosphonomethyl)glycine). The acidity constants of H2pfa- and H2ampa± as well as the stability constants of the [M(Hpfa)], [M(pfa)]-, [M(Hampa)]+, and [M(ampa)] complexes, where M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Cu(2,2′-bipyridyl)2+, Cu(1,10-phenanthroline)2+, Zn2+, or Cd2+, have been determined by potentiometric pH titrations in aqueous solution at 25° and I = 0.1M (NaNO3). The structures of isomeric complexes and the connected intramolecular equilibria are deduced and evaluated based on the equilibrium constants measured and those calculated via the pKa values of the above mentioned ligands and previously established log K vs. pKa straight-line plots (H. Sigel et al., Helv. Chim. Acta 1992, 75, 2634) for a simple phosphonate-M2+ coordination. pfa forms stronger complexes than ampa with all the above mentioned metal ions, with the single exception of [Cu(ampa)] which is slightly more stable than [Cu(pfa)]-. In neutral solutions, more precisely at pH of ca. 6, pfa complexes of alkaline-earth-metal ions retain one phosphonate-bound proton, [M(Hpfa)], while those of the transition-metal ions chelate with the trianionic ligand, pfa3-. In accord with increasing ligand-basicity, the stability-constant order for all metal-ion complexes is oxalate 〉 pfa 〉 pyrophosphate but, owing to proton competition in pyrophosphate, in neutral solutions metal-ion complexation of pfa3- competes with P2O74-. With ampa alkaline-earth-metal ions interact only with the phosphonate group of even the dianionic ligand (though Mg2+ appears to form a low fraction of a [Mg(ampa)] chelate) while transition-metal ions form chelates which are comparable in stability to those of glycinate.
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  • 197
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    X-Ray Crystal Structure of the 2-Phenyladamant-2-yl Cation (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1773-1780 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The crystal structure of the Sb2F11 salt of the 2-phenyladamant-2-yl cation, 1 · Sb2F11, was determined at 183 K (P21/c, R1 = 0.0652, σ(C—C) = 0.02 Å), because earlier published results indicated a charge delocalization from the cationic C(2) into the σ framework (C—C hyperconjugation) and a bending of the C(2) bridge. In the structure of 1, a displacement of the C(2) bridge by 7.8(12)° from the symmetrical position and C—C bond-length deviations from expectation values were found which are in agreement with preferential C—C hyperconjugation on one face of C(2). The interactions of 1 with two Sb2F11 counterions nearest to C(2) also indicate different behaviour of the two faces of C(2). The benzylic resonance in 1 is confirmed.
    Additional Material: 5 Ill.
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  • 198
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    Facile Preparation of (±)-12-Epiprostaglandins from 7-Oxabicyclo[2.2.1]hept-5-en-2-one via an all-cis-formyllactone related to Corey lactoneA preliminary communication of one part of this work was published [1]. (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1781-1790 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The bicyclic monoselenoacetal 7, easily obtained from (±)-7-oxabicyclo[2.2.1]hept-5-en-2-one (6) via a radical addition-acyl migration sequence, was converted to racemic 12-epiprostaglandins 3 and 4. The key intermediate was the all-cis-formyllactone 2b related to Corey lactone (see 12; Scheme 1). The presence of a (tert-butyl)-dimethylsilyl protective group for the 11-OH substituent (prostaglandin numbering) was found to be crucial in avoidingβ -elimination and epimerization during the Wittig-Horner reaction (Scheme 2). Epimerization at C(12) at the formyllactone stage (see 2b) was also possible and gave the known precursor 1b of naturally occurring prostaglandins and analogs.
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  • 199
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    Stability of Charge-Transfer Complexes of CS2 with PH3 and its derivatives: Ab initio MRSDCI/CASSCF StudyDedicated to Prof. Jan Linderberg, an excellent theoretician and marvelous friend, on the occasion of his 60th birthday (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1810-1816 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: While trialkylamines and dialkyl(phenyl)amines do not react with CS2 in the sense of an addition reaction, the analogous phosphines react smoothly. Attempts to interpret the reaction course on the basis of semiempirical, HF, MP2, and MP4 calculations of energy changes failed completely. To understand why Me3P or Me2PhP react so vigorously (liquid phase, 300 K) with CS2, CASSCF and MRSDCI calculations must be carried out.
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    URL: http://dx.doi.org/10.1002/hlca.19940770712
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  • 200
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    Synthesis and Complexation Properties of a New Class of Receptors based on a cone-configurated tetra-p-(tert-butyl)calix[4]arene and bipyridyl subunits (1994)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 77 (1994), S. 1817-1825 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 0The bipyridyl-armed tetra-p-(tert-butyl)calix[4]arenes 1-5 were synthesized from tetra-p-(tert-butyl)-calix[4]arene A and 6-(bromomethyl)-6′-methyl-2,2′-bipyridine (B) by direct base-strength-driven regioselective O-alkylation or by stepwise procedures. Preliminary complexation studies of the ligands 1-3 with CuI affording the complexes 6-8 are described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19940770713
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