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  • 1985-1989  (3,095)
  • 1987  (3,095)
  • General Chemistry  (1,002)
  • Organic Chemistry  (684)
  • Biochemistry and Biotechnology  (560)
  • Engineering  (448)
  • Engineering General  (448)
  • Rat  (195)
  • Biochemistry  (133)
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Years
  • 1985-1989  (3,095)
Year
Keywords
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 92 (1987), S. 473-477 
    ISSN: 1432-2072
    Keywords: Opiates ; Morphine ; Naloxone ; Place preference ; Saccharin ; Genetic strain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two strains of rats — LC2-Hi and LC2-Lo — selected for high and low self-stimulation rates, respectively, were tested for responses to opiates and to naloxone using conditioned place preference paradigm. In the two experiments which used opiates as UCS, conditioning was carried out in the non-preferred compartment while in the experiment which used naloxone, conditioning was performed in the preferred compartment. The preference changes were determined on the basis of times spent in the compartments before and after conditioning with drugs. LC2-Hi rats showed positive changes in the preference to the initially non-preferred side when morphine or heroin (5 mg/kg and 1 mg/kg, respectively) were used; no such effect was observed with LC2-Lo rats. Both lines exhibited aversive reactions to naloxone by diminishing the time spent in the environment paired with this drug, but again the response of LC2-Hi animals was significantly larger than the response of LC2-Lo rats. Chronic intake of a sweet solution (3 mM saccharin for 4 weeks) tended to amplify the aversive reaction to naloxone in both lines. It may be inferred from the present findings that there exists a common genetic factor, as revealed by the conditioned place preference paradigm, underlying positive reinforcing properties of opiates and aversive effects of naloxone.
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 91 (1987), S. 119-121 
    ISSN: 1432-2072
    Keywords: Successive discrimination ; Chlordiazepoxide ; Naloxone ; Benzodiazepines ; Opiates ; Nonreward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Naloxone reduces the effects of chlordiazepoxide on punishment and on acquisition of differential reinforcement of low rates of response. The present experiments tested whether naloxone also reduces the effects of chlordiazepoxide on a second type of nonreward schedule — successive discrimination. Rats were tested on a variable interval baseline of responding for food with signalled intrusion periods when food was no longer available. Naloxone (3 mg/kg IP) failed to change the effects of chlordiazepoxide (5 mg/kg IP) on either acquisition or performance of this successive discrimination. DRL and successive discrimination differ both in their timing of events and their use of explicit visual stimuli. If these or similar parametric differences account for the present results they considerably weaken conventional accounts of the control of behaviour by reward omission.
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  • 103
    ISSN: 1432-2072
    Keywords: Pituitary-adrenal function ; Behavioral despair ; Clomipramine ; Anti-depressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction between the effects of chronic electrical tail shock and clomipramine (CMI) on exploratory activity, behavioral despair and pituitary-adrenal function was studied in adult male rats. Both CMI and shock administered alone significantly reduced exploratory activity in a novel environment (holeboard). Neither interaction nor additive effects were observed when the two treatments were combined. In contrast, chronic shock increased the immobility in the forced swimming test (behavioral despair) and this effect was completely prevented by concomitant CMI administration. Pituitary-adrenal function was not significantly influenced by any of the treatments. The results indicate that: (a) chronic CMI treatment prevented some but not all behavioral changes caused by chronic shock, and (b) no interaction with basal and stress levels of pituitary-adrenal hormones was observed.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 91 (1987), S. 345-351 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Latent inhibition ; Conditioned suppression ; Animal model of schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioral paradigm in which animals learn to ignore a repeatedly presented stimulus not followed by meaningful consequences. We previously reported that LI was disrupted following the administration of 1.5 mg/kg dl-amphetamine. The present experiments investigated the effects of 6 mg/kg dl-amphetamine administration on LI in a conditioned emotional response (CER) procedure consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, the drug was administered in a 2×2 design, i.e. drug-no drug in pre-exposure and drug-no drug in conditioning. LI was obtained in all conditions. In Experiment 2, animals were given either 5 days of 6 mg/kg amphetamine pretreatment and amphetamine in pre-exposure and conditioning or 7 days of saline. LI was not obtained under amphetamine, but this outcome reflected a state-dependency effect. In Experiment 3, animals received either 5 days of amphetamine pretreatment and amphetamine in pre-exposure, conditioning and test or 8 days of saline. LI was obtained in both the placebo and amphetamine conditions. Experiments 4a and 4b compared the effects of two drug doses, 1.5 (4a) and 6 mg/kg (4b), administered in pre-exposure and conditioning. LI was abolished with the 1.5 mg/kg dose but not with the 6 mg/kg dose.
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  • 105
    ISSN: 1432-2072
    Keywords: SK & F 38393 ; Behavioural assessment ; Stereotypy ; Behavioural check list ; Grooming ; Dopamine ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioural effects of the D-1 dopamine receptor agonist SK & F 38393 were assessed in the intact adult rat using a conventional stereotypy rating scale and a rapid time sampling behavioural check list procedure. This combination technique allowed description of the nature of any behavioural response and quantification of the number of counts of individual behaviours. Using this combined procedure, SK & F 38393 clearly failed to induce typical stereotyped behaviour. However, in the well-habituated animal, SK & F 38393 dose-dependently increased the number of recordings of non-stereotyped sniffing, locomotion and grooming; some occasional rearing was also noted. An unusual pattern of intense grooming behaviour was a characteristic response to this drug. Using the resolved R-and S-enantiomers of SK & F 38393, promotion of sniffing, locomotion, rearing and grooming resided stereoselectively in the R-configuration. Under appropriate experimental conditions, specifically a requirement for prolonged habituation and the use of a rapid sampling behavioural check list to supplement the rating scale, it is possible to demonstrate that SK & F 38393 is behaviourally active in the whole animal.
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  • 106
    ISSN: 1432-2072
    Keywords: DSP4 ; Noradrenaline ; d-Amphetamine ; Operant behaviour ; Variable-interval schedules ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of d-amphetamine (0.1–3.2 mg/kg) on performance in variable-interval 1-min and variable-interval 12-min schedules of positive reinforcement was examined in ten rats treated with the selective noradrenaline neurotoxin DSP4 and 12 control rats. In the control group d-amphetamine had a dose-dependent suppressant effect on response rates maintained under variable-interval 1-min; under variable-interval 12-min, response rates were increased by low doses and suppressed by higher doses of the drug. In the case of both schedules, lower doses of d-amphetamine were more suppressant and higher doses less suppressant in the DSP4-treated group than in the control group. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum (determined by high-performance liquid chromatography) were reduced to approximately 15% of control levels in the DSP4-treated rats. The results indicate that treatment with DSP4 attenuated both the facilitatory and the suppressant effects of d-amphetamine on variable-interval performance. A formal model couched in terms of Herrnstein's (1970) equation is put forward to account for these results. It is suggested that the noradrenergic pathways emanating from the locus caeruleus are involved in both the facilitatory and suppressant effects of d-amphetamine on operant behaviour.
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  • 107
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    Psychopharmacology 92 (1987), S. 215-218 
    ISSN: 1432-2072
    Keywords: Ethanol ; Naloxone ; Locomotor activity ; Open field ; Active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The action of naloxone (0.5 and 2 mg/kg IP) on the behavioural effects of a low (2 g/kg PO) and a high dose (4 g/kg PO) of ethanol was studied in rats. Ethanol at the low dose increased spontaneous motility, enhancing open-field external ambulations and reducing shuttle-box latency. All these effects were antagonized by naloxone. Ethanol at the high dose produced hypomotility, decreasing open-field external ambulations and impairing shuttle-box performance. In this case, naloxone also reduced the ethanol effect, but its action was less consistent. Therefore, although mechanisms other than a specific opioid receptor blockade by naloxone must be considered, an involvement of opioid peptides in the effects of ethanol cannot be discounted.
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  • 108
    ISSN: 1432-2072
    Keywords: Place preference ; Heroin ; β-endorphin ; Naloxone ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of β-endorphin as a possible mediator in the reinforcing properties of opiates was investigated using a conditioned place preference paradigm. Heroin, a synthetic opiate known to have reinforcing properties, produced a strong preference for an environment previously paired with heroin injection at all doses tested (0.25, 0.5, 1.0, 2.0 mg/kg SC). No such place preference was observed following saline injections. Rats also showed dose-dependent place preference for the environment paired with β-endorphin when injected intracerebroventricularly (significant dose was 2.5 μg). At higher doses (5.0 and 10.0 μg) rats showed no preference for the paired environment, but were catatonic. Pretreatment with naloxone (0.04, 0.2, 1.0 mg/kg SC) attenuated the rewarding effect of β-endorphin (2.5 μg) at all doses tested. The lowest dose of naloxone which had no aversive effect when tested alone could also significantly block the positive effect of β-endorphin. The reinforcing dose of β-endorphin (2.5 μg) also produced an increase in locomotor activity, when tested in photocell cages. This suggests that the hyperactivity induced by β-endorphin may contribute to the preference for an environment previously paired with the same drug. The reinforcing effect of β-endorphin is most probably mediated by the mu and/or delta opioid subtype receptor, since β-endorphin has a high affinity for these receptors. These results demonstrate positive reinforcing properties of β-endorphin in the central nervous system.
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  • 109
    ISSN: 1432-2072
    Keywords: Apomorphine ; Conditioned dopaminergic activity ; Stereotyped behaviour ; Dopamine autoreceptors ; Dopamine metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated whether pharmacological effects of the dopamine agonist apomorphine can be conditioned by establishing an association of apomorphine administration with exteroceptive cues. Apomorphine was repeatedly administered and subsequently, the rat was put into a test cage and exposed to an acoustic and an olfactory stimulus (“conditioned rats”). Control animals (“pseudoconditioned” rats) were treated with the same pharmacological schedule of apomorphine not temporally associated with the stimuli. On the test day, both groups were injected with saline and exposed to the stimuli described. The stereotyped behaviour produced by large doses of apomorphine (0.5 or 2.0 mg/kg SC), namely sniffing, licking and gnawing, could be conditioned in a pronounced way. During the conditioning period, a change in the stereotypies was observed with regard to the time-course (earlier occurrence) and to the character of the stereotypies (from sniffing to licking and gnawing), when 0.5 mg/kg apomorphine was used, but not with the dose of 2.0 mg/kg. The conditioned responses showed a relatively uniform distribution during the observation period with some increase towards the end of the observation period. Some signs produced by a low dose of apomorphine (0.07 mg/kg SC), namely hypomotility and ptosis, but not yawning, could also be conditioned, although in a less pronounced way. An intermediate dose of apomorphine (0.18 mg/kg SC) produced both signs observed after large doses and those observed after a small dose, occurring alternatingly. Both types of signs could be conditioned using this dosage. Conditioning did not alter striatal or mesolimbic dopamine turnover. These results suggest that only behavioural signs due to an activation of postsynaptic dopamine receptors, but also some symptoms produced by an activation of dopamine autoreceptors can be conditioned.
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  • 110
    ISSN: 1432-2072
    Keywords: Conflict ; Anxiety ; GABA inhibition ; Epilepsy ; Benzodiazepine antagonist ; Benzodiazepine inverse agonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proconflict and electrocorticographic effects of drugs acting on the benzodiazepine (BDZ)/GABA/chloride-ionophore receptor complex were studied in rats in an attempt to correlate their anxiogenic and epileptogenic activities. Evidence for proconflict activity was assessed by means of an operant conflict procedure based on the simultaneous reward and punishment of a conditioned task, while epileptogenic properties were assessed by monitoring the electrocorticogram (ECoG) of free-moving rats. Pentylenetetrazole and picrotoxin, which act through a site on the chloride channel, and the benzodiazepine (BDZ) inverse agonist FG 7142 showed epileptogenic alterations in the ECoG at doses, respectively, 8, 2 and 3 times higher than those eliciting a significant proconflict effect. For the partial inverse agonist CGS 8216, a ratio of about 60 was found while the BDZ antagonist Ro 15-1788 showed neither epileptogenic nor proconflict activity, except at the highest tested dose for the latter effect (40 mg·kg−1 PO). Inhibition of GABA transmission may mediate both anxiogenic and epileptogenic actions, and a link between these properties may exist as a continuous spectrum of negative intrinsic efficacy at the central BDZ/GABA/chloride-ionophore receptor complex.
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  • 111
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Midazolam ; GABA ; R0 15-1788 ; CGS 8216 ; FG 7142 ; Serotonin ; 8-OH-DPAT ; Methysergide ; Amygdala ; Conflict ; Successive discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interactions between the benzodiazepines (BZs) chlordiazepoxide (CDP) and midazolam (MDZ), the BZ antagonist R0 15-1788, the inverse BZ receptor agonists CGS 8216 and FG 7142, γ-aminobutyrate (GABA), serotonin (5-HT), the 5-HT2 antagonist methysergide and the putative 5-HT agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were investigated using peripheral and intra-amygdaloid treatments. A multiple schedule consisting of rewarded, nonrewarded (Time out: TO) and conflict periods was used to compare in parallel effects on successive discrimination between rewarded and nonrewarded periods and punished responding. The three components were presented in both a fixed order (Experiment 1) and a random order (Experiments 2 and 3). Intra-amygdaloid treatments with GABA and the BZs selectively increased rates of punished responding. CDP given systemically, on the other hand, increased both TO and conflict rates, suggesting an additional impairment of discrimination, which was more marked in the random than the fixed order condition. R0 15-1788, CGS 8216 and FG 7142 given by both routes counteracted the anti-conflict effects of CDP given centrally or systemically. However increases in TO rates induced by IP CDP were antagonized only by IP treatments with these compounds. The two inverse agonists, but not R0 15-1788, also counteracted increases in punished responding which were found after intra-amygdaloid GABA infusions. In Experiments 2 and 3 where baseline rates of pressing in Conflict periods were sufficiently high to detect decreases, CGS 8216 and FG 7142 reduced responding below control level, suggesting a specific anxiogenic activity. Evidence for effects of R0 15-1788 by itself was inconclusive. 5-HT injected into the amygdala also reduced punished responding below control level, whereas methysergide increased it with both central and peripheral treatment. Effects of 8-OH-DPAT varied according to route of administration. With IP treatment Conflict rates were increased, but after amygdaloid infusion both TO and Conflict rates were marginally reduced below control level, with a more consistent depression of punished responding. These results provide evidence that effects of BZs on punished responding are mediated by a GABAergic system which includes the lateral/basolateral amygdala, but which does not participate in BZ-induced disruption of discrimination. They also indicate that the antagonistic effects of CGS 8216 and FG 7142 involve a decrease in GABA transmission, and that these compounds may also be anxiogenic. Finally, the results suggest that 5-HT utilizes the same system for regulating resistance to punishment, but plays no significant part in reward-nonreward successive discrimination, which is impaired after systemic BZs.
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  • 112
    ISSN: 1432-2072
    Keywords: LY165163 ; Stereotypy ; pCPA ; 5-MeODMT ; Apomorphine ; Serotonin ; Dopamine ; 5-HT1A agonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc). LY165163 (1 mg/kg) increased striatal DOPA accumulation in animals treated with the aromatic amino acid decarboxylase inhibitor 3-hydroxy-benzylhydrazine (NSD 1015) (100 mg/kg ip). This increase was also found when the drug was given to animals pretreated with parachlorophenylalanine (pCPA) (150 mg/kg ip daily for 3 days). LY165163 (2 and 4 mg/kg sc) inhibited stereotyped behaviour induced by the dopamine (DA) agonist apomorphine (2 mg/kg sc). LY165163 (2, 4, 10 mg/kg sc) also inhibited stereotyped components of the 5-HT syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 5 mg/kg ip) which previous studies (e.g. Andrews et al. 1982) suggested to require DA (head weaving, reciprocal forepaw treading). Thus, while other 5-HT1A agonists such as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) cause stereotypy, this does not occur with LY165163, probably because the drug blocks DA receptors.
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  • 113
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    Psychopharmacology 93 (1987), S. 113-117 
    ISSN: 1432-2072
    Keywords: Ro 5-4864 ; Clonidine ; B-HT 920 ; Guanfacine ; Benzodiazepines ; CL 218, 872 ; Pentobarbitone ; Yohimbine ; Idazoxan ; Convulsions ; Rat ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The protective effect of various alpha2 adrenoceptor agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 was investigated against Ro 5-4864-induced convulsions in mice and rats. Clonidine and ICI 106270 exhibited a profound anticonvulsant effect while equivalent doses of guanfacine and B-HT 920 were less effective. The anticonvulsant effect of clonidine and ICI 106270 was reversed by pretreatment with yohimbine or idazoxan, indicating the involvement of alpha2 adrenoceptors in their protective effect. Diazepam, clonazepam, CL 218, 872 and pentobarbitone exhibited a different profile of protective action, as these agents protected the animals from apparent mortality as compared to clonidine and ICI 106270 which prolonged the latencies of jerk and convulsion. Modulatory effects of alpha2 adrenoceptors in central GABA function and multiple sites for Ro 5-4864-induced seizures are explained.
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  • 114
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    Springer
    Psychopharmacology 91 (1987), S. 363-368 
    ISSN: 1432-2072
    Keywords: Memory ; Neuropeptides ; Vasopressin ; Oxytocin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult male rats spend a great amount of time investigating novel juveniles. In contrast, rats re-exposed to the same juvenile 30 min after the initial exposure display little investigatory behavior. If the re-exposure occurs 2 h later, the juvenile is thoroughly investigated. These results have been interpreted to mean that rats form a transient memory for a particular juvenile. In the present study, memory was enhanced when the initial exposure to the juvenile was followed by another exposure to the same juvenile (retroactive facilitation) and impaired when exposure to the original juvenile was followed by exposure to another juvenile (retroactive interference). Arginine vasopressin had retroactive facilitating effects on social memory and these effects were blocked by the vasopressor antagonist dPTyr(Me)AVP. Moreover, the antagonist had retroactive interfering effects, since it impaired the recognition of a familiar juvenile. Oxytocin shared the same inhibitory pattern of action. These results suggest that neurohypophyseal peptides may have a prepotent role in modulating the mnemonic processing of chemosensory information associated with social interactions.
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  • 115
    ISSN: 1432-2072
    Keywords: Chronic neonatal antidepressant treatment ; Desipramine ; Zimeldine ; Active (REM) sleep deprivation ; Open field behavior ; Alcohol intake ; Monoamines ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To study the relationship between neonatal antidepressant administration, active (REM) sleep and adult alcohol-related behavior, rat pups were treated daily with 5 mg/kg despramine (DMI) or 25 mg/kg zimeldine SC from the 6th to the 19th postnatal days. Movement sensitive mattress (“SCSB”) measurements showed that zimeldine treatment suppressed active sleep throughout the whole treatment period, but DMI was more effective during the first 8 days than during the last treatment days. At the age of 70 days, the zimeldine-treated rats expressed a selective increase of some components of activity in the open field test, and the DMI rats had a higher defecation score compared to the controls. Furthermore, the zimeldine-rats responded with a decrease in ambulation in the open field to an alcohol dose which generally stimulates locomotion in rats. At the age of 3 months the DMI and zimeldine rats showed increased voluntary intake of 10% (v/v) alcohol. Measurement of brain monoamines revealed that the neonatal treatment with DMI or zimeldine interfered with the normal development and function of the monoamine neuronal systems: the concentrations of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), and their metabolites were altered in several brain regions. The results thus suggest that neonatal treatment with DMI or zimeldine suppresses active sleep and has an influence on later alcohol-related behavior, possibly due to a long-lasting defect in brain monoaminergic transmission.
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  • 116
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Attention ; Discrimination ; Dopamine-Noradrenaline interaction ; Dorsal noradrenergic bundle ; alpha-Flupenthixol ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments examined the effects of lesions of the dorsal noradrenergic bundle (DNAB), induced by 6-hydroxydopamine (6-OHDA), on the behavioural response to systemic and intra-accumbens amphetamine, using a rat analogue of Leonard's 5-choice serial reaction time task for humans. Although the 6-OHDA DNAB lesion produced a profound depletion of cortical noradrenaline (NA) (to around 5% of control levels) it did not impair any aspect of performance on this task. Both systemic and intra-accumbens amphetamine increased behavioural measures of impulsivity of responding, but neither impaired discriminative accuracy in the sham-operated control rats. However, the DNAB lesioned rats did show a discriminative impairment following both low doses of systemic amphetamine, and intra-accumbens amphetamine. The latter effect was antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha-flupenthixol. The DNAB lesion did not alter the effect of amphetamine on any other behavioural measure, including speed and impulsivity of responding. These results suggest that although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens.
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  • 117
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    Pflügers Archiv 408 (1987), S. 438-443 
    ISSN: 1432-2013
    Keywords: Tubuloglomerular feedback ; Rat ; Furosemide ; Proximal tubule ; Micropuncture ; Kidney ; Entrainment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies in rat kidneys have demonstrated that oscillations in the proximal intratubular pressure are a prominent feature of the tubulo-glomerular feedback mechanism (TGF) operating during free flow conditions. The purpose of the present study was to investigate whether a subpopulation of synchronized, interacting nephrons could be detected. In group A nephrons, i.e., nephrons with a high probability of having their afferent arterioles arising from the same interlobular artery, 29 out of 33 pairs of nephrons were found to show synchronized pressure oscillations. In group B nephrons, not expected to have this common origin of their afferent arterioles, only 1 out of 23 pairs was found to be synchronized. The standard deviation of the frequency differences was 0.063 cycles per minute in group A nephron pairs and 0.202 cycles per minute in group B pairs (p〈0.05), showing the greater homogeneity in frequency in group A. Furthermore, nephrons having synchronized pressure oscillations were found to interact with each other. Thus, perturbation of the proximal tubular pressure oscillations in one nephron by loop microperfusion affected the amplitude of the pressure oscillations in the non-perfused nephron; and reactivation of pressure oscillations in one nephron was followed by reactivation of oscillations in the non-perfused nephron. Thus, the present results show that there exists a well defined subpopulation of nephrons, in which the TGF-mediated proximal pressure oscillations are synchronized. This synchronization is a result of interaction between the different nephrons. It is suggested that the interaction is a consequence of “cross-talk” between the TGF signals from the different nephrons concerned, transmitted along the afferent arterioles, and probably also along a part of the interlobular artery.
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  • 118
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    Archives of toxicology 59 (1987), S. 443-447 
    ISSN: 1432-0738
    Keywords: Rat ; Cadmium ; Injection route ; Teratogenesis ; Maternal liver damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i. v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25–2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i. p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.
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  • 119
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    Archives of toxicology 60 (1987), S. 77-80 
    ISSN: 1432-0738
    Keywords: n-Hexane ; Pharmacokinetics ; Man ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of inhaled n-hexane in rat and man were compared. In the rat metabolism was saturable. Up to 300 ppm, the metabolic rate was directly proportional to the concentration in the atmosphere, reaching 47 μmol/(h· kg). Only 17% of n-hexane was exhaled unchanged. Above 300 ppm, the amount of n-hexane in the body rose with increasing atmospheric concentrations from 1.6 up to a limiting value of 9.6, which corresponded to the thermodynamic distribution coefficient of n-hexane between the organism and the atmosphere. Up to 3000 ppm, the rate of metabolism increased to 245 μmol/ (h· kg); only a slow further increase was found up to 7000 ppm (285μmol/(h· kg)). In man the steady-state concentrations of n-hexane were about 1 ppm. The metabolic clearance was 1321/h, and n-hexane accumulated to a factor of 2.3 in the organism. The thermodynamic distribution coefficient was calculated to be 12. Twenty per cent of n-hexane in the body was exhaled unchanged. At low concentrations the rate of metabolism of n-hexane is limited in both species by transport to the enzyme system. Under these conditions the rate of metabolism of n-hexane should not be influenced by xenobiotics which induce the n-hexane metabolizing enzyme system.
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  • 120
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    Archives of toxicology 60 (1987), S. 325-327 
    ISSN: 1432-0738
    Keywords: Bromofenofos ; Dephosphate bromofenofos ; Embryolethality ; Teratogenicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bromofenofos (BF) and dephosphate bromofenofos (DBF) were administered at equimolar doses to rats on day 10 of pregnancy. The dams were killed on day 21, and the fetuses were removed, weighed and examined by routine teratological methods. BF caused a significant increase in fetal resorptions at 58.2 mg/kg. Approximately 69% of the implants were resorbed at this dose level. In rats given DBF equimolar to 58.2 mg/kg BF, the resorption rate was 81.9%. Administration of BF resulted in a dose-dependent decrease in fetal body weights which was significant at 29.1 mg/kg or more. DBF caused a significant decrease in fetal body weights, beginning at 25.1 mg/ kg equimolar to 29.1 mg/kg BF, and the decreased fetal body weights were almost the same between BF and DBF. BF at 58.2 mg/kg induced significant gross and skeletal malformations, with incidences of 35.6 and 27.6%, respectively. In rats given DBF equimolar to 58.2 mg/kg BF, gross and skeletal malformations were seen in 54.5 and 61.5% of the fetuses, respectively. There were similarities in the types of malformations observed between BF and DBF. Both compounds induced no significant internal malformations. It was concluded from these results that the embryolethal and teratogenic effects of BF is due to its metabolite, DBF, which cannot respond to cholinesterase inhibition.
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  • 121
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    Archives of toxicology 59 (1987), S. 341-345 
    ISSN: 1432-0738
    Keywords: Rat ; Lead ; Brain ; Myelin basic protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postnatal exposure of rats to lead has been shown previously to cause CNS hypo-myelination. Since rats intoxicated with lead often show retarded growth, the superimposed malnutrition, which as such can cause hypomyelination, may contribute to myelin deficit. In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1–15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation (Sundström et al. 1983). The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15–200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.
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  • 122
    ISSN: 1432-0738
    Keywords: Drug-metabolizing enzymes ; Liver ; Rat ; Hepatocarcinogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression, inducibility, and regulation of four different cytochrome (cyt.) P-450 isoenzymes (PB1, PB2, MC1, and MC2) NADPH-cytochrome P-450 reductase, the glutathione transferases (GSTs) B and C and microsomal epoxide hydrolase (mEHb) have been studied during nitrosamine-induced hepatocarcinogenesis using immunohistochemical techniques. The investigations revealed basic differences in the expression of the individual drug metabolizing enzymes in the course of neoplastic development. While the two GSTs and mEHb were increased in all preneoplastic and benign neoplastic lesions, the levels of the distinct cyt. P-450 isoenzymes were characteristically different from each other. Following initial changes in the expression of these enzymes in early preneoplastic lesions (i. e., increase of cyt. P-450 PB1 versus slight decrease of the other cyt. P-450 isoenzymes), a continuous reduction of all cyt. P-450 isoenzymes was observed during the further course of hepatocarcinogenesis. In progressed neoplastic nodules, all cyt. P-450-isoenzymes and NADPH cyt. P-450 reductase were decreased to varying extents. Treatment of animals with inducers of the monooxygenase system, such as phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls, led to a rather heterogenous pattern of enzyme alterations in preneoplastic and neoplastic lesions. Following administration of phenobarbital, some islets responded to the same degree as the surrounding tissue, others were less or not at all inducible and a few of the lesions showed a prominent increase in cyt. P-450 PB2 and NADPH-cyt. P-450 reductase levels. The interesting finding that these two enzymes always showed concurrent changes may be indicative of a common regulation. Similar to phenobarbital, an induction of cyt. P-450 isoenzymes within carcinogen-induced lesions was also observed following administration of 3-methyl-cholanthrene or polychlorinated biphenyls. The results demonstrate that drug-metabolizing enzymes are abnormally regulated in carcinogen-induced lesions. The multiplicity of enzyme deviations within individual lesions and especially the enzyme inducibility strongly suggest that the focal enzyme alterations result from genotoxic effects of the carcinogen on regulatory systems of a higher order rather than from mutational events in individual structural genes.
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  • 123
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    Archives of toxicology 60 (1987), S. 319-324 
    ISSN: 1432-0738
    Keywords: Bromofenofos ; Organophosphorus anthelmintic ; Embryolethality ; Teratogenicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bromofenofos, an organophosphorus anthelmintic, was administered by gavage to rats as a single dose (50 mg/kg) on one of days 6 through 14 of pregnancy. The dams were killed on day 21, and the fetuses were removed, weighed and examined by routine teratological methods. A significant increase in fetal resorptions occurred after administration on days 9 through 13, with a maximum on day 10. Approximately 72% of the implants were resorbed after administration on day 10. Fetal body weights were significantly decreased when dams were treated on day 8 or later. The greatest decrease in fetal body weights was observed on day 10, when the fetuses weighed less than the controls by about 44% on the average. The incidence of fetuses with gross, skeletal and internal malformations was significantly increased on days 8 through 10, on days 8 through 11 and on days 8 and 9, respectively. Although various types of malformations were observed, most of them occurred on day 8, when no significant increase in fetal resorptions did occur. Cleft lip, short tail, brachygnathia, anal atresia, absence of genital tubercle, fused pelvic legs and perineal testicles were seen on day 8 as gross malformations. Skeletal malformations mainly affected the vertebrae and ribs. Major internal malformations on day 8 were hydronephrosis, hydroureter, anophthalmia, cleft palate, agenesis of the bladder and renal agenesis. Anophthalmia and/or microphthalmia were observed on days 8 through 10, with the highest incidence on day 9. To further determine the no-effect levels for embryolethal and teratogenic effects, a single dose of 10, 20, 30 or 40 mg/kg was administered by gavage to rats on days 8 or 10 of pregnancy. The no-effect levels of single oral dose for embryolethal and teratogenic effects were considered to be 40 and 30 mg/kg, respectively.
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  • 124
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    Archives of toxicology 61 (1987), S. 21-26 
    ISSN: 1432-0738
    Keywords: m-Xylene inhalation ; Xenobiotic enzymes ; Lung effects and morphology ; Blood concentrations ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were exposed to 0, 75, 150 or 300 ppm (1 ppm=1 cm3/m3=4.35 mg/m3) m-xylene for 24 h and then killed. In the lungs, the cytochrome P-450 decreased to 45, 13 and 20% of the control value with the increasing exposure intensity and the activity of 7-ethoxycoumarin O-deethylase to 70, 27 and 14%, respectively. The activity of epoxide hydrolase increased slightly after exposures both at 150 (1.6-fold) and 300 cm3/m3 (1.4-fold), while the other measured drug-metabolizing enzyme activities showed no consistent changes. The non-protein sulfhydryl group content of the lungs was not affected. The concentrations of m-xylene in blood indicated that the solvent uptake increased in the different exposure groups more than expected, based on atmospheric concentrations alone. Morphologic studies of the lungs with scanning electron microscopy showed no apparent changes after exposure to 300 cm3/m3 or after a high oral dose (2 ml/kg/day, 3 days). Inhalation exposure to m-xylene for 5 weeks (7 h/day, 4 days/week) at a concentration of 300 ppm lowered the contents of cytochrome P-450 in rat lungs to 65% and the activity of 7-ethoxycoumarin O-deethylase to 41% without any other marked effects on the other drug-metabolizing enzymes or on the levels of non-protein sulfhydryl groups. In this study, the selective destruction of cytochrome P-450 in rat lung could be shown both after acute and subacute exposures and at concentrations low enough to warrant occupational concern.
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  • 125
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    Archives of toxicology 60 (1987), S. 394-396 
    ISSN: 1432-0738
    Keywords: Barbiturate poisoning ; Pentobarbitone ; Phenobarbitone ; Gastric emptying ; Gastrointestinal transit ; Peristaltic reflex ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anaesthetic doses of pentobarbitone (50 mg/kg) were found to inhibit gastric emptying and gastrointestinal transit in the rat. Gastric emptying was more profoundly suppressed than gastrointestinal transit. Phenobarbitone (150 mg/kg) had a similar effect. Since pentobarbitone and phenobarbitone also blocked the peristaltic reflex in the isolated small intestine of the guinea-pig, it would appear that the inhibitory effect of anaesthetic doses of barbiturates on gastrointestinal motility is mainly due to a direct action on the digestive tract. Together with the observation that considerable amounts of phenobarbitone were found in the stomach of an intoxicated patient 3 days after drug intake, these results might indicate that gastric lavage should also be considered in the treatment of protracted barbiturate poisoning.
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  • 126
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    Archives of toxicology 59 (1987), S. 328-331 
    ISSN: 1432-0738
    Keywords: Aristolochic acid ; Toxicology ; Acute toxicity ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acute toxic effects of aristolochic acid (AA) were tested in rats and mice of both sexes. Oral or intravenous administration in high doses was followed by death from acute renal failure within 15 days. Histologically, the predominant features were severe necrosis affecting the renal tubules, atrophy of the lymphatic organs and large areas of superficial ulceration in the forestomach, followed by hyperplasia and hyperkeratosis of the squamous epithelium. The LD50 ranged from 56 to 203 mg/kg orally or 38 to 83 mg/kg intravenously, depending on species and sex.
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  • 127
    ISSN: 1432-0738
    Keywords: Silver toxicity ; Cultured macrophages ; Cell death ; Ultrastructure ; Lipid peroxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of silver on cultured mouse peritoneal macrophages were examined by estimation of cell survival and by light and electron microscopy. Additon of silver lactate to the culture medium at final concentrations of 40 and 80 μM resulted in coagulation necrosis and rapid cell death. At lower concentrations cell structure appeared normal. However, the rate of cell death at 20 μM silver lactate was increased as compared to controls. Silver, visualized by physical development/autometallography, was invariably located in lysosomes. The production of malondialdehyde in mouse liver of silver-treated mice as compared to controls was also examined. This lipid peroxidation product had increased to the same amount in animals treated with silver for either 3 days or with only one silver injection 4 h before examination. This study has demonstrated that silver affects viability and structure of cultured macrophages, possibly due to induction of lipid peroxidation, as demonstrated to occur in the liver of silver-exposed mice.
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  • 128
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    Archives of microbiology 148 (1987), S. 150-154 
    ISSN: 1432-072X
    Keywords: Bacteroides ; Vesicles ; Ultrastructure ; Cellulolytic bacteria ; Rumen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In 3-day-old cultures of Bacteroides succinogenes grown on filter paper, no cell division was observed. When grown on cellulosic substrate, bacteria exhibited vesicles clustered within cell wall pockets. In 2 day-old filter paper cultures, cells adhered tightly to the substrate. Twenty to 30% of them were dividing. There were cell wall pockets in about 25% of the bacteria, but no vesicles. Whether they adhered to the cellulosic substrate or not, and irrespective of the age of the bacteria, storage polysaccharides were found in the form of dense granules in the cytoplasm. It would appear that vesicles are not essential for cellulose degradation, but are rather a sign of ageing of the cells.
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  • 129
    ISSN: 1432-2072
    Keywords: Antidepressants ; Ergometrine ; Neuroleptics ; Nucleus accumbens ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assesses the behavioural significance of the (-)sulpiride binding sites in the rat nucleus accumbens that bind antidepressants with high affinity and neuroleptics with low affinity. The effects were measured by intra-accumbens injections of typical and atypical antidepressants or neuroleptics, either given alone or in combination with ergometrine (1 μg/0.5 μl per side) on rat locomotor activity in a familiar environment. In addition, the after-effects of the combined ergometrine-drug treatment upon locomotor activity were analyzed. The antidepressants shared a common profile of effects. Thus, none of the antidepressants significantly altered locomotor activity in naive rats. Moreover, each antidepressant produced after-effects which were similar to those elicited in the acute ergometrine experiments. However, some antidepressants (amitriptyline and zimelidine) potentiated the ergometrine response, while other antidepressants (desipramine, mianserin and clorgyline) attenuated this response. (-)Sulpiride (0.5 μg) decreased the ergometrine response when given together with ergometrine or 48 h earlier. Haloperidol had to be given in a dose that was 20 times higher than that of (-)sulpiride in order to be effective. Clozapine (1–10 μg) failed to alter the ergometrine response when given together with ergometrine. Only (-)sulpiride produced a dose-dependent attenuation of locomotor activity in naive rats. The present data are discussed in terms of the hypothesis that drugs with antidepressive effects mediate their behavioural effects via mesolimbic (-)sulpiride binding sites.
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  • 130
    ISSN: 1432-2072
    Keywords: DRL ; Chlordiazepoxide ; Naloxone ; Benzodiazepines ; Opiates ; Learning ; Nonreward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The opiate antagonist naloxone can completely or partially reverse the effects of the benzodiazepines on appetitive behaviours and conflict tasks involving electric shook. If naloxone changes the anxiolytic action of the benzodiazepines it should, theoretically, be effective in tasks employing nonreward as well as those employing shock. We tested naloxone and chlordiazepoxide on acquisition and performance of a nonreward task, DRL. With both continuous administration during acquisition of DRL, and intermittent administration during stable performance, chlordiazepoxide (5 mg/kg IP) increased burst responding and shifted the peak of the inter-response time (IRT) distribution curve to shorter IRTs. Naloxone (3 mg/kg IP) blocked the effects of chlordiazepoxide on acquisition of DRL. Naloxone (3 mg/kg and 10 mg/kg IP) did not change the effects of chlordiazepoxide on well-learned performance of the DRL schedule. These results show that endogenous opiates could mediate some but not all of the actions of the benzodiazepines. They also suggest that state-dependent and “truly anxiolytic” effects of the benzodiazepines (McNaughton 1985) may have different pharmacological substrates.
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  • 131
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; Tail-flick ; Classical conditioning ; Rat ; Antinociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats, ethanol increases the latency of the tail-flick reflex to radiant heat. Three experiments examined the contribution of classical conditioning to the acquisition of tolerance to this antinociception. Experiment 1 showed that the antinociception produced by ethanol was dose dependent. The results of Experiment 2 demonstrated that rats exposed to a series of ethanol injections paired with a distinctive environment developed tolerance to this antinociception. In Experiment 3, tolerance was more pronounced in animals that had been exposed to ethanol and tested in the distinctive environment than in animals that had received ethanol in a nondistinctive environment. In contrast to previous reports in the literature, these results show that animals need not practice the tail-flick reflex while intoxicated in order to develop tolerance. Additionally, the data suggest that classical conditioning may contribute to tolerance to the antinociceptive effects of ethanol.
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  • 132
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    Psychopharmacology 93 (1987), S. 19-24 
    ISSN: 1432-2072
    Keywords: Imidazole ; Imidazole derivatives ; Lisuride ; Sexual behaviour ; Aggressiveness ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult male rats were treated intraperitoneally (IP) with imidazole (IMID), distilled water or saline prior to administration of lisuride either IP or intracerebroventricularly (ICV) at doses too low by themselves to elicit the behavioural signs of mounting and aggressiveness, typically induced by higher doses of this drug. Pretreatment with distilled water or saline, or the procedure of injection alone, stimulated mounting in some of the animals. At a certain range of doses IMID induced a marked increase in both mounting and aggressive posturing in the same animals, while at higher doses mounting ceased, violent aggressive behaviour appeared and some of the rats died. Seven IMID derivatives were used on the lisuride-test: N-methylimidazole, 2-methylimidazole, 4-methylimidazole, N-acetylimidazole, 4-imidazoleacetic acid, clonidine and cimetidine. Only 4-imidazoleacetic acid was completely ineffective with respect to controls. All the other drugs enhanced aggressive behaviour to varying degrees but proved to be less potent than IMID in inducing mounting, and clonidine reduced mounting at all the doses tested.
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  • 133
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    Psychopharmacology 91 (1987), S. 139-146 
    ISSN: 1432-2072
    Keywords: Autoreceptors ; Bromocriptine ; CQ 32-084 ; Dopamine ; Exploratory behaviour ; Mesulergine ; Multivariate statistics ; Pergolide ; 3-PPP ; Rat ; Sulpiride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of six putative dopamine receptor agonists on exploratory behaviour in rats were assessed: pergolide, (+)- and (-)-3-PPP, bromocriptine, mesulergine and CQ 32-084. Behaviour was automatically recorded in a holeboard apparatus and the data were analysed by the novel multivariate statistical method of partial least squares. All six substances suppressed exploratory behaviour at low doses. Pergolide and (+)-3-PPP-induced stereotyped behaviour at higher doses. The suppression of exploration induced by pergolide was completely antagonised by sulpiride, partly antagonised by metoclopramide and weakly affected by haloperidol pretreatment. The effects of a low dose of (+)-3-PPP, bromocriptine or CQ 32-084, but not (-)-3-PPP or mesulergine, were antagonised by sulpiride. These findings support the hypotheses that pergolide, (+)-3-PPP, bromocriptine and CQ 32-084 inhibit exploration via stimulation of dopamine receptors. The present data do not substantiate the hypothesis that the suppression of exploration induced by (-)-3-PPP is mediated by stimulation of dopamine autoreceptors. A detailed analysis of the dose response curves for pergolide and (+)-3-PPP indicates that the latter compound may have effects in addition to those of a dopamine receptor agonist.
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  • 134
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    Psychopharmacology 91 (1987), S. 209-212 
    ISSN: 1432-2072
    Keywords: Intracerebral drug application ; Memory ; N. raphé magnus ; Clorgyline ; Pargyline ; Deprenyl ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 μl/min, 1–2 μl) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n=10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 μg per rat with intracerebral (n. raphé magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 μg C and 10 μg P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 μg P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D).
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  • 135
    ISSN: 1432-2072
    Keywords: Striatum ; Limbic ; Catalepsy ; GABA ; Muscimol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To establish the role of the GABA-ergic mechanism within the striatal-pallidal complex in hindlimb disturbances, forelimb disturbances and catalepsy and the relationship between these phenomena, the effects of the locally injected GABA agonist muscimol (0.5 μl per side) were investigated in rats using several specific tests of catalepsy. The time required for retracting free-hanging hindlimbs was dose-dependently prolonged by 2–10 ng muscimol. The time required for releasing a rod that was clasped between the forelegs of otherwise free-hanging rats was dose-dependently prolonged by 5–10 ng muscimol. Likewise, the time required for retracting the free-hanging forelimbs was dose-dependently prolonged over the same dose range. Finally, the time during which standing rats kept their forelimbs on a block of 9 cm height (the dependent variable used in “classic” tests of catalepsy) was only prolonged at the highest dose (10 ng) of muscimol. The effects of the latter dose, which lasted at least 30 min, were inhibited by the GABA antagonist bicuculline (50 ng) for a minimum period of 5 min. The present data show that the GABA-ergic mechanisms within the striatal-pallidal complex are involved in hindlimb disturbances, forelimb disturbances and catalepsy, and that catalepsy requires a stronger dysfunctioning of these GABA-ergic mechanisms than do disturbances in hindlimbs and forelimbs.
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  • 136
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    Psychopharmacology 92 (1987), S. 96-99 
    ISSN: 1432-2072
    Keywords: 5-HT ; l-5-HTP ; Anxiolytic ; Anxiogenic ; Drinking ; Conflict ; Vogel test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of l-5-HTP (25–400 mg/kg IP) following inhibition of the peripheral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg IP) was investigated in a test modified from Vogel's drinking conflict model. At 50 mg/kg an anti-conflict action was detected, while higher doses (100–400 mg/kg) decreased punished responding. A lower dose (25 mg/kg) had no effect. Non-specific effects — such as alterations in muscle tone, in motivation to drink or in the sensitivity to electrical shock — could not explain the anxiolytic- and anxiogenic-like actions of 50 and 100 mg/kg, respectively. The bi-phasic effect of l-5-HTP is discussed in terms of different subpopulations of central serotoninergic receptors, possibly exerting opposing influences on conflict responding. The study emphasises the importance of 5-HT mechanisms in anxiety, and the possibility of finding novel anxiolytics among drugs selectively affecting central 5-HT neurotransmission.
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  • 137
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    Psychopharmacology 93 (1987), S. 243-249 
    ISSN: 1432-2072
    Keywords: Vasopressin ; Desglycinamide-vasopressin ; Amphetamine ; Matching to position ; Memory ; Arousal ; Signal detection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of peripherally injected arginine vasopressin (AVP: 0–25 μg/kg), its desglycinamide analogue (DGAVP: 0–25 μg/kg), which is practically devoid of pressor activity, and d-amphetamine (AMP: 0–1.25 mg/kg) were studied using a delayed (0–32 s) matching to position task (Dunnett 1985). A limited hold for responding (20 s) was in operation. This task enables an accurate assessment of forgetting in rats. AVP reliably improved per cent correct performance, and this effect was substantiated by accuracy indices derived from signal detection theory (TSD). DGAVP, however, was inactive, suggesting that the parent peptide's pressor properties were responsible for its beneficial effects. AMP disrupted performance in a dose-related manner, and was the only substance to alter a TSD bias index (responsivity index, RI), indicating a degree of response repetition at the highest dose. These results are consistent with some earlier reports, and suggest that AVP may enhance memory by peripheral action, while AMP disrupts performance. Closer inspection of the data, however, suggested that the peptide reduced general responsiveness. A new index to measure bias (Sahgal 1987) suggested that AVP-treated subjects restricted their sample and choice responses to one side of the operant chamber, thereby achieving a spuriously high detection rate with few errors of commission (incorrect responses). It is concluded that AVP does not, after all, improve performance: on the contrary it has detrimental effects, and produces errors of omission (failure to respond).
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  • 138
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Simultaneous discrimination ; Control by S+ and S− ; General transfer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained in a Y-maze on a two-choice simultaneous black-white discrimination with either black or white as S+. Animals were then transferred to one of three discrimination tasks. In task 1 (New S−), a new stimulus, either vertical or horizontal stripes, was substituted for the original S−. In task 2 (New S+), a new stimulus, either vertical or horizontal stripes as in task 1, was substituted for the original S+. In task 3 (New S+/S−) animals were trained on horizontal-vertical discrimination. The pre-trial administration of 1 mg/kg d-amphetamine facilitated the acquisition of the original black-white discrimination with both black as S+ and white as S+. Likewise, the drug improved performance in all three transfer conditions. However, the course of learning in the three transfer tasks was different in the placebo- and amphetamine-treated animals. Amphetamine-treated animals were disrupted more by a change in S+ than by a change in S−, whereas the opposite pattern was evident in the placebo controls. When both discriminative stimuli were changed, placebo animals exhibited pronounced decrement in performance, whereas amphetamine animals exhibited excellent learning. The implications of these findings for the effects of amphetamine on discrimination learning are discussed.
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  • 139
    ISSN: 1432-2072
    Keywords: Trimethyltin ; Hippocampus ; Learning and memory ; Autoshaping ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The organometal neurotoxin trimethyltin (TMT), induces impaired learning and memory for various tasks. However, administration is also associated with other “non-specific” behavioral changes which may be responsible for effects on conditioned behaviors. To determine if TMT treatment causes a specific learning impairment, three experiments were done using variations of a delay of reinforcement autoshaping task in which rats learn to associate the presentation and retraction of a lever with the delivery of a food pellet reinforcer. No significant effects of TMT treatment were found with a short (4 s) delay of reinforcement, indicating that rats were motivated and had the sensorimotor capacity for learning. When the delay was increased to 6 s, 3.0 or 6.0 mg TMT/kg produced dose-related reductions in behaviors directed towards the lever. Performance of a group given 7.5 mg TMT/kg, while still impaired relative to controls, appeared to be better than the performance of groups given lower doses. This paradoxical effect was investigated with a latent inhibition paradigm, in which rats were pre-exposed to the Skinner boxes for several sessions without delivery of food reinforcement. Control rats showed retardation of autoshaping when food reinforcement was subsequently introduced. Rats given 7.5 mg TMT/kg exhibited elevated levels of lever responding during pre-exposure and autoshaping sessions. The results indicate that 7.5 mg TMT/kg produces learning impairments which are confounded by hyperreactivity to the environment and an inability to suppress behavior toward irrelevant stimuli. In contrast, low doses of TMT cause learning impairments which are not confounded by hyperreactivity, and may prove to be useful models for studying specific associational dysfunctions.
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  • 140
    ISSN: 1432-2072
    Keywords: Yawning ; Apomorphine ; 6-Hydroxydopamine ; Autoreceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apomorphine-induced yawning was studied in male rats with bilateral 6-hydroxydopamine lesions of the substantia nigra. Apomorphine 10, 20 and 50 μg/kg SC induced dose-dependent yawning in unoperated controls and animals with sham lesions. In the lesioned animals (in which the mean striatal dopamine depletion was 67%), the maximum yawning response rate was greatly attenuated with no evidence that the dose response curve was shifted in either direction. Furthermore, blockade of yawning in the lesioned animals was not simply due to suppression by other stereotyped behaviours, since there was no evidence of increased sniffing or chewing in these animals. These data provide further support for the hypothesis that apomorphine-induced yawning is mediated by dopamine autoreceptors and requires intact nigrostriatal projections.
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  • 141
    ISSN: 1432-2072
    Keywords: Animal model ; Catalepsy ; Neuroleptics ; Paw test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) and atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non-neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects.
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  • 142
    ISSN: 1432-2072
    Keywords: 5-HT1A receptors ; Anxiolytics ; Interactions ; Feeding ; Rat ; 5-HT autoreceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were examined. Gepirone dose-dependently increased feeding 2 and 4 h after injection, the magnitude of the response being larger than previously observed with any other 5-HT1A receptor ligand. Previous studies have suggested that buspirone and ipsapirone can block some of the behavioural effects of 8-OH-DPAT. However, gepirone, buspirone and ipsapirone did not inhibit feeding induced by 8-OH-DPAT. These results indicate that gepirone is a very efficacious appetite stimulant in rats and suggest that gepirone, buspirone and ipsapirone act as 5-HT autoreceptor agonists in the feeding model.
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  • 143
    ISSN: 1432-2072
    Keywords: Animal model of depression ; DMI ; Stress ; Saccharin ; Sucrose ; Saline ; Preference ; Anhedonia ; Corticosterone ; Glucose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats exposed chronically (5–9 weeks) to a variety of mild unpredictable stressors showed a reduced consumption of and preference for saccharin or sucrose solutions. Preference deficits took at least 2 weeks to develop and were maintained for more than 2 weeks after termination of the stress regime. Sucrose preference was unaffected by 1 week of treatment with the tricyclic antidepressant DMI but returned to normal after 2–4 weeks of DMI treatment. DMI did not alter sucrose preference in unstressed animals. No significant changes were seen in saline preference either during stress or following drug treatment. DMI reduced blood corticosterone and glucose levels, but stress did not significantly alter either measure. The results are discussed in terms of an animal model of endogenous depression.
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  • 144
    ISSN: 1432-2072
    Keywords: Noradrenaline ; Dorsal noradrenergic bundle ; 6-Hydroxydopamine ; Operant behaviour ; Herrnstein's equation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible role of the dorsal noradrenergic bundle (DNAB) in the maintenance of operant behaviour by positive reinforcement was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Twelve rats received bilateral injections of 6-hydroxydopamine (4 μg/2 μl) into the DNAB; ten rats received sham injections. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement affording reinforcement frequencies of 8–350 reinforcers per hour. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The values of both R max (the parameter of the equation expressing the theoretical maximum response rate) and K H (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) were significantly higher in the DNAB-lesioned group than in the sham-lesioned group. At the end of the behavioural experiment the rats were sacrificed for determination of catecholamine levels in the brain by high-performance liquid chromatography. The levels of noradrenaline in the neocortex and hippocampus of the DNAB-lesioned rats were approximately 10% of those of the sham-lesioned rats. The results indicate that destruction of the DNAB reduced the “value” of the reinforcer without impairing the animals' capacity to respond.
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  • 145
    ISSN: 1432-2072
    Keywords: Dopamine (DA) ; D-1 DA receptor agonist (SK&F 38393) ; D-2 DA autoreceptor agonist (B-HT 920) ; Combination ; Postsynaptic DA receptor-induced stereotyped behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postsynaptic dopaminergic behavioural effects of D-2 agonists can be promoted by concomitant D-1 receptor activation. The present experiment explored whether such effects could be elicited by the putative autoreceptor-selective D-2 agonist B-HT 920, when combined with the D-1 agonist SK&F 38393. Except for occasional jerks induced by B-HT 920, neither agonist caused significant dopaminergic stimulation when given separately, whereas combined treatment with SK&F 38393 and B-HT 920 induced clear-cut motor activation — particularly focused stereotyped licking and sniffing — in reserpine/AMT-pretreated rats. Both the D-1 antagonist SCH 23390 and the D-2 antagonist spiperone abolished these effects, while the SK&F/B-HT-induced stimulation was not significantly affected by the alpha2-blocker idazoxan. It appears that classical postsynaptic DA receptor-stimulatory properties of B-HT 920 can indeed be demonstrated, provided that sufficient D-1 receptor tone prevails.
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  • 146
    ISSN: 1432-2013
    Keywords: Cortical collecting tubule ; Rat ; ADH ; Principal cells ; Intercalated cells ; Barium ; Amiloride ; Ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanism of ion transport across principal cells of rat cortical collecting tubules (CCT) and its regulation by vasopressin (ADH) has been studied in the isolated perfused tubule. To amplify the response to ADH rats were treated with 5 mg I. M. desoxycorticosterone 4–9 days prior to the experiments. Addition of 2·10−10 mol·1−1 ADH increased the transepithelial voltage from −5.1 ±0.7 mV to −16.1±1.4 mV (n=37) and decreased the transepithelial resistance from 51±4 Ω cm2 to 39±2 Ω cm2 (n=33). Optical and functional differentiation of impalements of principal and intercalated cells was made and only data of principal cells are presented. ADH depolarized the apical membrane from 79±1 mV to 66±2 mV (n=26) and decreased the fractional resistance of the apical membrane from 0.76±0.04 to 0.70±0.04 (n=13). These ADH effects were prevented by 10−5 or 10−4 mol·1−1 luminal amiloride which hyperpolarized the apical membrane when added in the presence or absence of ADH. Apical and basolateral membranes were dominated by large K+ conductances and addition of 3 mmol·1−1 barium to bath or lumen perfusates increased transepithelial resistance almost two-fold, whereas luminal amiloride increased the transepithelial resistance only by 26–35%. Ouabain (0.5 mmol·1−1, bath) depolarized the basolateral membrane and decreased its K+ conductance. These effects were prevented by the simultaneous presence of apical amiloride suggesting that the only route of Na+ entry into the principal cells occurred via the amiloride sensitive Na+ conductance. We conclude that ADH stimulates Na+ reabsorption and K+ secretion in the rat CCT primarily by increasing the Na+ conductance in the apical cell membrane.
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  • 147
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    Pflügers Archiv 409 (1987), S. 492-498 
    ISSN: 1432-2013
    Keywords: Rat ; Micropuncture ; Sodium ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Micropuncture and clearance studies were performed on rats with chronic metabolic acidosis to evaluate the segmental handling of magnesium. Fractional magnesium excretion was 12.6±2.3% in acidemic rats (blood pH 7.17+0.2) compared to 5.1±1.3% of normal animals (blood pH 7.36±0.05). Ultrafilterable magnesium concentrations were similar in both normal and acidotic animals, 0.51±0.02 and 0.48±0.03 mM, respectively. Elevation of urinary magnesium excretion was due to diminished reabsorption in the loop of Henle and segments beyond the distal sampling site. Acute correction of the systemic acidosis with NaHCO3 infusions partially corrected the renal magnesium levels as fractional magnesium excretion fell from 12.6% to 3.1+0.75%. This was associated with enhanced reabsorption of magnesium in the loop. To determine if acidosis may compromise the renal conservation of magnesium, acidotic rats were subsequently placed on magnesium-restricted diets. Normal and acidotic animals adapted appropriately and to a similar extent when challenged by short-term magnesium-restricted diets. Accordingly, elevation of dietary acid intake and systemic acidosis leads to renal magnesium wasting which is due in part to diminished reabsorption in the loop of Henle. However, chronic acidosis does not compromise the renal adaptive response to dietary magnesium restriction.
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  • 148
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    Pflügers Archiv 409 (1987), S. 220-222 
    ISSN: 1432-2013
    Keywords: Rat ; isolated perfused kidney ; isolated perfused liver ; combination of
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interaction between hepatic and renal metabolism is found in many endocrine systems. We therefore developed a new experimental model, combining the isolated perfused rat kidney and rat liver. Krebs-Henseleit buffer with bovine serum albumin 67 g·1−1 and amino acids was recirculated to both organs through two rolling pumps, four 8 μm Millipore filters and two specially designed membrane lungs. The kidney was cannulated by a modification of the technique described by Nishiitsutsuji-Uwo 1967 and the liver was cannulated by a modification of the technique described by Hems 1966. Kidney function: Perfusion pressure 12.4±1.1 kPa (93±8 mmHg), flow 28±6 ml·min−1·g−1, FRNa 94.0±2.9%, GFR 491±191 μl·min−1·g−1, urine production 48±34 μl·min−1·g−1, FEK 60±36%. Liver function: Flow 25 ml·min−1 (fixed), portal vein pressure 12±3 cm H2O, bile flow 0.18±0.13 ml·h−1, oxygen consumption 2.0±0.2 μmol·min−1·g−1. Only minor differences were found between single perfusions (N=25) and combined perfusions (N=6). We conclude that it is possible to combine the isolated perfused rat kidney and rat liver without impairment of the function of either.
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  • 149
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    Pflügers Archiv 409 (1987), S. 194-199 
    ISSN: 1432-2013
    Keywords: Sodium transport ; Amiloride ; Colon ; Rat ; Ontogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate developmental changes in colonic sodium transport, the sensitivity of the transepithelial potential and short-circuit current to amiloride was investigated. The amiloride-sensitive short-circuit current (I sc Na ), which represents the electrogenic sodium transport through Na+ channels, rose significantly from day 5, reached a peak on day 10, and entirely disappeared after weaning. The maximum rate of electrogenic, amiloride-sensitive sodium transport was 12.0 μEq/cm2 · h. TheI sc Na was suppressed by adrenalectomy and/or premature weaning but not by a mineralocorticoid antagonist, spironolactone. On the contrary, treatments which increase aldosterone levels in vivo (low-sodium diet, furosemide-induced natriuresis, high dietary intake of potassium) stimulated theI sc Na . The effect of adrenalectomy increased during postnatal development. The sensitivity ofI sc Na to aldosterone was highest at the end of the weaning period. High-sodium diet, which causes a decrease in circulating aldosterone, was associated with a partial inhibition ofI sc Na (P〈0.016). These data suggest that the distal colon of neonatal rats can transport sodium via an electrogenic, amiloride-sensitive mechanism and that adrenocortical hormones exert the main regulatory control of this pathway.
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  • 150
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    Pflügers Archiv 409 (1987), S. 507-511 
    ISSN: 1432-2013
    Keywords: Vestibulo-ocular reflex ; Rat ; Serotonin ; Agonists and antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of intraventricular injection of serotonin (5-HT) and its agonists and antagonists on the amplitude of the vestibulo-ocular reflex were studied in chronic implanted rats. 5-HT (10−5 M) triggers an increase of the amplitude of the reflex which lasts 30 min. Similar results are obtained when N,N-dimethyl-5-methoxytryptamine (10−3 M) is introduced into the ventricular cannula. The increasing effects observed both with 5-HT and N,N-dimethyl-5-methyoxy-tryptamine are abolished by methiothepin, a potent antagonist of 5-HT receptors. Injection of indirect agonists like pargyline, a monoamine oxidase inhibitor, or fluoxetine, a potent inhibibitor of 5-HT reuptake, is followed by an increase of the amplitude of the vestibulo-ocular reflex. These results indicate that 5-HT can modulate the activity of the vestibulo-ocular pathway and muscular tone of extraocular muscles. Location and involvement of various modulating 5-HT sites are discussed.
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  • 151
    ISSN: 1432-1459
    Keywords: Myoadenylate deaminase ; Histochemistry ; Biochemistry ; Neuromuscular diseases ; Exertional myalgia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A histochemical assay was routinely performed of myoadenylate deaminase (MAD) in muscle biopsy specimens. MAD was absent in 13 cases, i.e. 2.9% of the specimens. In 10 cases the deficiency was confirmed biochemically. The diagnoses in the 13 patients were: polyneuropathy (n=5), infantile spinal muscular atrophy (n=3), congenital myopathy with type 2 fibre atrophy, facioscapulohumeral myopathy, polymyositis, myotonic dystrophy and hyperornithinaemia with gyrate atrophy of the retina. In contrast, 35 unrelated patients presenting with exercise-related muscle cramps or pains showed normal histochemical MAD activity. The biopsy specimens in all of these patients were essentially normal and in none of them was the diagnosis of a neuromuscular disease made. The results failed to confirm the association of MAD deficiency with aches, cramps and pains or exertional myalgia.
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  • 152
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    Pflügers Archiv 408 (1987), S. 543-551 
    ISSN: 1432-2013
    Keywords: Fibre types ; Fibre transformation ; Enzymes of energy metabolism ; Slow and fast skeletal muscle ; Rat ; Age ; Endurance training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of age and endurance training on muscle fibre characteristics were studied in a slow (m. soleus, MS) and in a fast (m. rectus femoris, MRF) skeletal muscle. Wistar rats at ages of 1, 2, 4, 10, and 24 months were used as experimental animals. The trained rats were put to run on a motor-driven treadmill 5 d/wk beginning from the age of 1 month. The body weights of the animals increased continuously throughout their lives. The muscle weights increased up to the age of 10 months, after which they tended to decrease. The trained adult rats had lower body weights as well as lower muscle weights than the untrained adult rats. The amount of the intramuscular lipid decreased with age, especially during the first months of life. The activity of isocitrate dehydrogenase (ICDH) decreased during the growth period in both muscles and remained more or less constant thereafter, whereas the activity of phosphofructokinase decreased with age only in MS. In MS, the trained animals tended to have higher ICDH activities than the untrained animals. The cross-sectional area of the different fibre types in both muscles increased up to the age of 10 months. The major fibre types, type I in MS and type IIB in MRF, were smaller for trained than untrained rats. The percentage number of the slower fibre types of both muscles — type I in MS and types I and IIA in MRF —increased with advancing age. The muscles of the trained animals contained higher percentages of the slower fibre types than those of the untrained rats. The present paper indirectly supports the opinion that not only the metabolic but also the contractile properties of different muscle cell types can be changed by age and long-term endurance-type physical training.
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  • 153
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    Naunyn-Schmiedeberg's archives of pharmacology 335 (1987), S. 255-260 
    ISSN: 1432-1912
    Keywords: Tyramine ; Neuropeptide Y ; Calcium-independence ; Desipramine ; Norepinephrine ; Vas deferens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of tyramine on the isolated vas deferens of rats was investigated. Tyramine induced a dose-dependent contraction which was blocked by phentolamine and disappeared in adrenergic denervated tissues. In the presence of an antiserum to neuropeptide Y (NPY), the contraction induced by concentrations of tyramine greater than 10 μM was markedly increased. In addition to inducing the release of 3H-norepinephrine (NE), tyramine evoked a concentration-dependent efflux of NPY-like immunoreactivity (NPYLI) from synaptosomal preparations. This action was not modified either by the removal of calcium ion from the medium or by the pretreatment with tetrodotoxin (0.5 μM). Desipramine suppressed the NPY-LI release induced by tyramine apparently by the inhibition of the uptake of tyramine is suggested by the significant positive correlation between the reduction of 4C-tyramine uptake and the inhibition of NPY-LI release induced by desipramine (r = 0.946). Therefore, we suggest that tyramine does induce the release of NPY from rat vas deferens, in addition to effecting NE secretion.
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  • 154
    ISSN: 1432-1912
    Keywords: (±)-Baclofen ; Micturition reflexes ; Rat ; Pelvic ganglia ; GABA B receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effect of (±)-baclofen on micturition reflexes was investigated in urethane-anaesthetized rats. A ‘low’ dose of (±)-baclofen (0.5 mg/kg i.v.) barely affected the early phase of the transurethral cystometrogram (CMG) which involves activation of a spinal vesico-vesical excitatory reflex. 2. At a higher dose (2.5 mg/kg i.v.) (±)-baclofen suppressed both the spinal and supraspinal components of the bladder response to transurethral saline filling. 3. When the bladder was filled by the transvesical route a series of regular voiding cycles was obtained which are due to activation of a supraspinal vesico-vesical excitatory reflex. In this model, voiding efficiency of the rat bladder was markedly reduced even after a low dose of (±)-baclofen (0.5 mg/kg) and almost suppressed at 2.5 mg/kg. 4. (±)-Baclofen reduction of voiding efficiency was mainly ascribable to an inhibitory effect on the expulsive phase of the voiding cycle which, in rats, depends critically upon the activation of a reflex which induces a twitch-like contraction of urethral/periurethral skeletal muscles. 5. (±)-Baclofen produced a small inhibition of the pinching-induced somatovesical excitatory reflex. (±)-Baclofen (2.5 mg/kg i.v.) produced also a marked but transient inhibition of bladder contractions induced by preganglionic nerve stimulation. However the time course of this effect was markedly shorter as compared to the long lasting suppression of voiding cycle observed with this same dose of the drug. 6. (−)-Baclofen, which is more potent than (±)-baclofen as a GABA B receptor agonist, affected bladder response to transurethral or transvesical filling in a manner similar to that observed with the racemate, but at lower doses (0.1–0.5 mg/kg i.v.). 7. These findings indicate that: a) (±)-baclofen affects markedly various types of reflexes concerned with micturition; b) a central site seems the main determinant of its action; c) at a low dose level inhibition of the reflex activation of urethral/periurethral skeletal muscles rather than the detrusor is a main target for (±)-baclofen action and d) GABA B receptors may modulate excitatory neurotransmission in rat pelvic ganglia.
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  • 155
    ISSN: 1432-2307
    Keywords: Human heart ; Papillary muscle ; Myocardial hypertrophy ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural study using various electron microscopical techniques has been conducted on biopsy material from the hypertrophied papillary muscle of the human heart. About 75% of the myocardial cells were classified as hypertrophic with diameters ranging from 15 εm to 53 εm. The increased cell diameter appeared to be the result of an elevated amount of mitochondria and contractile material. The hypertrophied myocytes displayed a general ultrastructural organization in many ways similar to that of the normal sized myocytes. However, the former cells were characterized by focal deposits of excess laminar coat material and abnormal Z-band patterns as well as of multiple intercalated discs. The preferential sites for the production of new sarcomere elements appeared to be in the subsarcolemmal and intercalated disc regions. Adjacent myocardial cells were interconnected by collagen bundles, and, by an elaborate collagen-fibril-microthread-granule lattice. The surface folds were linked to each other by surface cables, which probably constituted a separate category of extracellular material of unknown function. Intramembranous particles were abundant in the sarcolemma proper but scarce in the membranes of the sarcoplasmic vesicles. Such particles were also observed in the lipofuscin granular membrane and in the membranes surrounding the lipid droplets. A framework of transverse cytoskeletal filaments interconnected the Z-bands of adjacent myofibrils and anchored the contractile material to the sarcolemma as well as to the nucleus. A large and lobulated nucleus containing well developed nucleoli together with an abundance of sarcoplasmic free and membrane-attached ribosomes, were interpreted as morphological signs of enhanced synthetic activity in the hypertrophied cell. Degenerative phenomena on the other hand were confined to lysosomal degeneration of worn-out cell constituents that were manifested by the numerous lysosomes and aggregates of lipofuscin granules. Abnormal Z-band patterns as seen in the present material were interpreted as an initial stage in the formation of new contractile elements.
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  • 156
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    Virchows Archiv 411 (1987), S. 267-273 
    ISSN: 1432-2307
    Keywords: Corticotropic adenoma ; Ultrastructure ; Pituitary oncocytoma ; Choroid Plexus carcinoma ; Mitochondrial morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The report documents a silent, oncocytic, ACTH-producing ectopic anterior pituitary tumour in a 6-year-old boy. The invasive intrahemispheric neoplasm had no connection with the pituitary gland, the sella turcica or the sphenoid sinuses. The apparent similarities existing between this tumour, some choroid plexus carcinomas and steroid-producing neoplasms are discussed.
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  • 157
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    Virchows Archiv 411 (1987), S. 283-291 
    ISSN: 1432-2307
    Keywords: Tumor invasion ; Ultrastructure ; Desmoplasia ; Squamous cell carcinoma ; Lung parenchyma ; Basal lamina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using ultrastructural methods we studied the interaction of tumour cells and lung parenchyma in deep areas (i.e., more than about 3 mm from the tumour surface) of 50 bronchogenic squamous cell carcinomas. The tumour periphery, studied previously, had shown organized associations of tumour cells and lung epithelial cells and a surprising lack of invasion of non-epithelial tissue compartments. The deeper areas, where the tumour cells and the lung parenchyma had been in contact for longer periods, consisted of irregular groups of tumour cells and desmoplastic stroma which was very similar to granulation tissue. The deeper areas also contained many intact lung epithelial cells, arranged in compressed and distorted alveolar structures. Where non-neoplastic epithelial cells and tumour cells had direct contact, they formed common junctional complexes and basal laminae. In part of the tumours, the cells were largely devoid of a basal lamina. However, in most instances a continuous basal lamina surrounded every tumour cell group studied, even when these formed irregular strands or seemed to be completely isolated.
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  • 158
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    Theoretical and applied genetics 74 (1987), S. 177-187 
    ISSN: 1432-2242
    Keywords: Barley ; Grain development ; Mutants ; Ultrastructure ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Eleven Na-azide induced barley shrunken endosperm mutants expressing xenia (sex) were characterized genetically and histologically. All mutants have reduced kernel size with kernel weights ranging from 11 to 57% of the wild type. With one exception, the mutant phenotypes are ascribable to single recessive mutant alleles, giving rise to a ratio of 3∶1 of normal and shrunken kernels on heterozygous plants. One mutant (B10), also monofactorially inherited, shows a gene dosage dependent pattern of expression in the endosperm. Among the 8 mutants tested for allelism, no allelic mutant genes were discovered. By means of translocation mapping, the mutant gene of B10 was localized to the short arm of chromosome 7, and that of B9 to the short arm of chromosome 1. Based on microscopy studies, the mutant kernel phenotypes fall into three classes, viz. mutants with both endosperm and embryo affected and with a non-viable embryo, mutants with both endosperm and embryo affected and with a viable embryo giving rise to plants with a clearly mutant phenotype, and finally mutants with only the endosperm affected and with a normal embryo giving rise to plants with normal phenotype. The mutant collection covers mutations in genes participating in all of the developmental phases of the endosperm, i.e. the passage from syncytial to the cellular endosperm, total lack of aleurone cell formation and disturbance in the pattern of aleurone cell formation. In the starchy endosperm, varying degrees of cell differentiation occur, ranging from slight deviations from wild type to complete loss of starchy endosperm traits. In the embryo, blocks in the major developmental phases are represented in the mutant collection, including arrest at the proembryo stage, continued cell divisions but no differentiation, and embryos deviating only slightly from the wild type.
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  • 159
    ISSN: 1432-0878
    Keywords: Cholecalcin (vitamin D-dependent calcium-binding protein) ; mRNA ; Uterus ; In situ hybridisation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The molecular cloning of a cDNA fragment synthesised from rat duodenal mRNA coding for cholecalcin (calbindin), a 9000 Mr vitamin D-induced calcium-binding protein (CaBP), has been previously described. DNA/RNA hybridisation assays have been used to examine CaBP mRNA production in the uterine horns and duodena of pregnant (21 day) rats using the cloned CaBP cDNA. Northern hybridisation studies showed that the 32P cDNA sequence hybridised to a single 500–600 nucleotide species in both the uterus and the duodenum, thus demonstrating identical CaBP mRNA processing in both tissues. Dot blot hybridisation studies showed that the CaBP mRNA concentration was greatest in the duodenum while that of the uterine horns was about 10% of the duodenal level. The observed differences in CaBP mRNA levels correlate well with the in vivo CaBP concentrations. In situ hybridisation histochemistry using 3H cDNA revealed that CaBP mRNA visualised by silver grains was found in all the parts of the endometrium and the myometrium. However, CaBP mRNA was more concentrated in the outer and inner muscular fibres and in the luminal cells of the endometrium than in the stroma cells. These results demonstrate that the CaBP gene is expressed in specific cells of the rat uterus.
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  • 160
    ISSN: 1432-0878
    Keywords: Subcommissural organ ; Innervation ; Neu rophysins ; Mesotocin ; Immunocytochemistry ; Ultrastructure ; Snake, Natrix maura
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The subcommissural organ (SCO) of the snake Natrix maura was studied by use of the immunoperoxidase procedure. Primary antisera against bovine neurophysins (Nps I + II, OXY-Np), oxytocin (OXY), mesotocin (MST), arginine-vasotocin (AVT), somatostatin (SOM), β-endorphin (END) and bovine Reissner's fiber were used. A conventional ultrastructural study, with special emphasis on the nerve fibers present in the SCO, was also performed. Nerve fibers containing immunoreactive OXY-Np and MST were seen to reach the SCO. The staining of adjacent sections with the anti-Reissner's fiber serum showed that the OXY-Np- and MST-immunoreactive fibers were distributed among the cell bodies and processes of the ependymal secretory cells. No fibers containing immunoreactive OXY, AVT, SOM or END were found in the SCO. The ultrastructural analysis revealed in the SCO the presence of nerve fibers filled with electron-dense granules, 170–210 nm in diameter. Although a direct apposition between these fibers and the SCO cells was frequently seen, no synaptic differentiations were identified. Structures identical to the Herring bodies (found in the neurohypophysis) were seen in the SCO.
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  • 161
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Aminoglutethimide ; Corticosterone ; Morphometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of a 7-day administration of aminoglutethimide (AG) on the adrenal zona fasciculata were examined in “normal” and dexamethasone/ACTH-treated rats. There was a 70–74% decrease in the concentration of corticosterone in blood, but no conspicuous qualitative changes suggesting cell degeneration occurred. Morphometry showed that AG induced a significant hypertrophy of the zona fasciculata and its parenchymal cells only in “normal” animals, which was due to an increase in the volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum. This response to AG was considered to be non-specific and mediated by the enhanced secretion of ACTH following the decrease in the blood level of corticosterone. AG administration significantly increased the volume of the lipid-droplet compartment and the number of intramitochondrial lipid-like inclusions in both groups of animals. These changes were interpreted as the morphological counterpart of the AG-induced block of cholesterol utilization in steroid synthesis.
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  • 162
    ISSN: 1432-0878
    Keywords: Astrocytes ; Ependymal cells ; Circumventricular organs ; Tight junctions ; Orthogonal arrays of particles ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ependymal cells in the ventricular wall and in several circumventricular organs of the rat were compared by means of freeze-fracturing. In principle, tight junctions and orthogonal arrays of particles (OAP) do not coexist in the cells bordering the ventricular wall: (1) Ordinary ependymal cells of the rat possess OAP and are devoid of tight junctions. (2) Epithelial cells of the rat choroid plexus are connected by tight junctions; OAP are lacking here. In some cases, however, tight junctions and OAP coexist in the same cell. In the boundary zone between choroid plexus and ependyma of the rat, the density of OAP is very low, whereas the tight junctions are well developed. In the subfornical and the subcommissural organ (SCO) of the rat both structures are poorly developed; in the SCO they occur segregated in different membranous areas. An overview of the literature confirms that tight junctions and OAP mostly exclude each other. The possibility that in astrocytes and ependymal cells tight junctions may have been replaced by OAP during phylogeny is briefly discussed.
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  • 163
    ISSN: 1432-0878
    Keywords: Teeth ; Dental pulp ; Periodontium ; Neurofilament protein ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of nerve fibers in molars, periodontal ligament and gingiva of the rat shows a complex pattern. Decalcified material including the alveolar bone was sectioned in three different planes and stained by means of immunohistochemistry for detection of the neurofilament protein (NFP); the immunoreactive neural elements were clearly visualized in three-dimensional analyses. NFP-positive nerve fibers formed a subodontoblastic plexus in the roof area of the dental pulp; some of them entered the predentin and dentin directly through the dentinal tubules. This penetration was found mainly in the pulp horn, and was limited to a distance of about 100 μm from the pulpo-dentinal junction. In the periodontal ligament, NFP-positive nerve fibers were found densely distributed in the lower half of the alveolar socket. Two types of nerve terminals were recognized in the periodontal ligament: free nerve endings with tree-like ramifications, and expanded nerve terminals showing button- or glove-like shapes. The former tapered among the periodontal fibers, some even reaching the cementoblastic layer. The latter were located, frequently in groups, within the ligament restricted to the lower third of the alveolar socket. A well-developed plexus of NFP-positive nerves was revealed in the lamina propria of the free gingiva, the innervation being denser toward the epithelium of the gingival crevice. The characteristic distribution of NFP-immunoreactive nerve fibers revealed in this study is discussed in relation to region-specific sensations in the teeth and surrounding tissues.
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  • 164
    ISSN: 1432-0878
    Keywords: Epididymis ; Ductus deferens ; Myosin ; Actin ; Fibronectin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The postnatal maturation of regions of the epididymis and intragonadal segment of the deferens duct was studied in the rat by light-and transmission electron microscopy. Maturation of the genital duct starts in the distal cauda epididymidis and ductus deferens after one week of life, and one week later, in the more cranial segments of the epididymis. Epithelial principal cells and peritubular contractile cells are structurally mature 35 days after birth. The synchronous changes of these cells indicate that the same factors control their postnatal maturation. The epithelial principal cells obtain an endocytotic apparatus and long stereocilia, whereas peritubular cells acquire contractile features. These changes are associated with a progressive increase in the immunoreaction for smooth muscle actin in both cell types. Smooth muscle myosin is detected in the apical region of the epithelial cells and the peritubular cell cytoplasm by day one of postnatal development. The differentiation of contractile cells in the wall is accompanied by progressive organization of the pericellular matrix into a continuous basement membrane. Although fibronectin is visible at birth, it is gradually removed from the tubule wall.
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  • 165
    ISSN: 1432-0878
    Keywords: Cardiac muscle cells ; Extracellular matrix ; Collagen fibers and filaments ; Immunohistochemistry ; Rat ; Hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The morphology, composition, and function of struts that interconnect the lateral surfaces of cardiomyocytes were examined in the hearts of rats and hamsters. Methods included brightfield and fluorescent light microscopy, secondary and backscatter scanning electron microscopy, and transmission electron microscopy in conjunction with silver stain, cationic dye, and antibody to type-I collagen. These studies reveal a twisted, beaded appearance and a complex substructure of collagen fibrils embedded in a ground substance that has a positive reaction with cationic dye. A hierarchy of patterns of branching and attachment was seen among intercellular struts ranging in diameter from 0.1 μm to several urn. The hypothesis that struts tether not only the surfaces but the contractile lattices of laterally adjacent myocytes is supported by the following: (a) the attachments of struts to the collagen weave of the sarcolemma, often lateral to the level of Z bands, (b) the presence of collagen type I in a composite material arrangement, (c) the relative dispositions and configurational changes of struts and myocyte surfaces in various physiological states and induced, non-physiological perturbations of cardiac muscle, (d) the corrugated sarcolemmas with infoldings near Z bands, and (e) the continuity of intracellular filaments from Z bands to the inner aspect of the sarcolemma in relaxed and contracted myocytes. Implications of struts acting as tethers and sites for storage of energy in the motions of myocytes during the cardiac cycle are discussed.
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  • 166
    ISSN: 1432-0878
    Keywords: GABA-treatment ; Superior cervical ganglion ; Synaptic plasticity ; Morphometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The superior cervical ganglion (SCG) of adult rats was exposed to γ-aminobutyric acid (GABA) by means of long-term microapplication. Serial sections were cut from GABA-treated and control ganglia, and subsequently the fine structure of individual synapses was investigated. The quantitative analysis of structural parameters of studied synapses showed that significant changes consisting of (1) a reduction in size of presynaptic axon terminals, (2) a decrease in the number of synaptic vesicles, and (3) a diminution in the extent of the postsynaptic membrane thickening at the dendritic side developed as an effect of GABA-treatment. These results provide morphological evidence that long-term application of GABA to the SCG exerts a combination of effects on both presynaptic and postsynaptic elements. It is suggested that the structural changes observed in the fine structure of individual synapses within the SCG may play an integral role in the development of the synaptogenetic action of GABA.
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  • 167
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    Cell & tissue research 249 (1987), S. 325-329 
    ISSN: 1432-0878
    Keywords: Renin release ; Epithelioid cells ; Osmosensitivity of renin release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Superfusion with hypoosmotic solutions stimulates renin release from rat epithelioid cells adherent to isolated glomeruli. This stimulatory effect may be related to the observed swelling of the secretory granules; the swelling may markedly increase the probability of pre-exocytotic fusions between the granule and cell membranes, and consequently increase the frequency of exocytotic events.
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  • 168
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    Cell & tissue research 249 (1987), S. 421-425 
    ISSN: 1432-0878
    Keywords: Cholinergic synapses ; Ultrastructure ; Exocytosis ; Non-synaptic release ; Neuropeptides ; Carassius auratus ; Rana pipiens ; Wistar white rat ; Hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Nerve terminals forming typical synapses with adrenal chromaffin tissues have been examined in the goldfish, frog (Rana pipiens), hamster and rat. Presumptive secretory inclusions present in the terminals are of two distinct types. Electron-lucent synaptic vesicles 30–50 nm in diameter are densely clustered adjacent to membrane thickenings and presumably discharge their contents into the synaptic clefts. Secretory granules (i.e. large dense-cored vesicles) 60–100 nm in diameter are more abundant in other parts of the terminals. Sites of granule exocytosis have been observed in each of the animals investigated. They are usually encountered within apparently undifferentiated areas of plasmalemma and only rarely occur within synaptic thickenings. Granule exocytosis from within synaptic terminals and chromaffin gland cells is most readily observed in specimens exposed, prior to fixation, to saline solutions containing both tannic acid, and 4-aminopyridine and/or elevated levels of K+. These findings show that the pattern of secretory discharge, involving both synaptic and non-synaptic release, which is widespread in invertebrate central nervous systems, is also characteristic of vertebrate, peripheral cholinergic terminals.
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  • 169
    ISSN: 1432-0878
    Keywords: Exocrine pancreas ; Secretion granules ; Effect of feeding ; Carbachol ; Stereology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The size, number and volume per cell of secretion granules in rat exocrine pancreas have been measured using stereological techniques. The changes which occur as a result of feeding starved animals (90 min) or stimulating lobular fragments in vitro with carbachol are documented. In fasted animals mean acinar cell volume was estimated as 1670 μm3 and the cells contained an average of around 450 secretion granules with a corrected mean diameter of 0.70 μm. They occupied around 7% of cell volume. After feeding mean cell volume was about 1300 μm3 and the cells contained an average of about 190 granules per cell with a mean diameter of 0.58 μm. They occupied 3% of cell volume. A shift in the size frequency distribution of granule diameters occurred as a result of feeding. In vitro experiments in which lobules were induced to secrete with carbachol (10μM, 3 h, 37° C) had a similar effect. Mean cell volume was reduced from around 1760 μm3 to 1360 μm3, mean granule number from around 420 per cell to 180 per cell and the volume density of granules was reduced from about 8% to 3% of cell volume. There was no significant change in mean granule diameter or shift in the size-frequency distribution of granule diameters. Incubation of tissues with cycloheximide (1 mM, 3 h, 37° C) did not prevent secretion by carbachol but it prevented replacement of granules. As a consequence, depletion by carbachol was greater in the presence of cycloheximide, the granules being reduced to around 110 per cell and to only 2.5% of cell volume. We conclude that feeding causes a preferential loss of larger granules and that during secretion replacement of granules occurs. Some of these granules are smaller than those evident in the glands of starved animals.
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  • 170
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    Cell & tissue research 249 (1987), S. 437-442 
    ISSN: 1432-0878
    Keywords: Angiotensin II ; Glomerulus ; Salmo gairdneri ; Seawater-adaptation ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effect of angiotensin infusion on the glomerular ultrastructure of freshwater- and seawater-adapted rainbow trout, Salmo gairdneri, has been examined by scanning and transmission electron microscopy. Adaptation of trout to seawater resulted in epithelial podocyte flattening, primary process broadening and apparent loss of foot processes in almost all glomeruli, features which were uncommon in freshwater-adapted trout. Similar changes were induced by infusion of freshwater-adapted animals with angiotensin, suggesting that the renin-angiotensin system plays a role in the modification of glomerular epithelial ultrastructure. Adaptation of trout to seawater also reduced glomerular diameter, but infusion of freshwater-adapted animals with angiotensin did not mirror this effect. Infusion of angiotensin into seawater-adapted animals increased the overall thickness of glomerular basement membrane by increasing the lamina rara interna and lamina densa. This did not occur when freshwater-adapted fish were either infused with angiotensin or adapted to seawater. These findings suggest that other humoral systems are involved in the control of glomerular diameter and basement membrane thickness as part of an integrated response to increased environmental salinity.
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  • 171
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    Cell & tissue research 249 (1987), S. 443-449 
    ISSN: 1432-0878
    Keywords: Different strains ; Adrenal cortex ; Zonation ; Cellular composition ; Sex differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The zonation and cellular composition of the adrenal cortex of intact mature male and female rats of different strains (Chbb Thomm, CFY) and three strains of Wistar rats (W1, W2 and W3) at the age of 84–90 days were compared using morphometry. Both absolute and relative adrenal gland weights were higher in female than male rats. Rats of W3 and Chbb Thomm strains had the largest adrenals. These differences depended upon the higher volume of the zona fasciculata (ZF) and zona reticularis (ZR) in the W3 and Chbb Thomm strains than in the remaining animals. Females had larger adrenocortical zones than corresponding males. The average volume of the ZF cell ranged in males from 1589 μm3 (W1 strain) to 2111 μm3 (Chbb Thomm) and in females from 2249 μm3 (W1 strain) to 2894 μm3 (W3 strain). The average nuclear volume of the ZF cells was higher in female rats whereas there were no strain-and sex-differences in the size of zona glomerulosa (ZG) and ZR cells. The total number of parenchymal cells per pair of adrenals varied markedly among the studied strains, with the highest number in W3 and Chbb Thomm females. W3, Chbb Thomm and CFY females had larger number of parenchymal cells than males; the reverse was true for W1 strain whereas no differences were found among W2 male and female rats.
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  • 172
    ISSN: 1432-0878
    Keywords: Leydig cells ; Ethane dimethanesulphonate ; Ultrastructure ; Degeneration ; Resistance ; Rodents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The morphological response of the testis of rats, guinea pigs, Syrian hamsters and mice to treatment with the cytotoxin ethane dimethanesulphonate was examined using light and electron microscopy. One to two days after a single administration of ethane dimethanesulphonate to adult rats, guinea pigs, and hamsters, the Leydig cells showed marked ultrastructural alterations suggestive of degeneration and cell death. The former alterations included karyopyknosis, cytoplasmic vesiculation and accumulation of lipid inclusions and large lipofuscin bodies. Fragments of necrotic Leydig cells were often engulfed by the interstitial tissue macrophages. The morphology of the seminiferous epithelium of these three species was unchanged from the morphology observed in vehicle-injected control animals. In contrast, multiple injections of ethane dimethanesulphonate given to mice produced no ultrastructural alterations to Leydig cells yet the seminiferous epithelium exhibited disruption of spermatogenesis. Although the Leydig cells of the mouse appear resistant to ethane dimethanesulphonate, this agent exerts a selective cytotoxic action upon Leydig cells of the rat, guinea pig and hamster thus identifying ethane dimethanesulphonate as a useful chemical for future endocrine and physiological studies of testicular function in three common laboratory species.
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  • 173
    ISSN: 1432-0878
    Keywords: Macula densa ; Intercellular spaces ; Ultrastructure ; Frusemide ; Tubulo-glomerular feedback ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In situ drip-fixation of superficial glomeruli and tubules in the rat kidney verified the results obtained from high pressure perfusion fixation studies indicating that distinct spaces normally exist between the cells of the macula densa. Following treatment with frusemide these intercellular spaces between the macula densa cells became closed in both drip-fixed and perfusion-fixed kidneys. These findings suggest that the variability of extracellular compartmentation found in the macula densa is unlikely to be an artifact but most likely represents changes in the in vivo status of the macula densa.
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  • 174
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Liver ; Nucleolus ; 4-amino-pyrazolo(3,4-d)pyrimidine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The nucleolar ultrastructural changes produced in adrenal zona fasciculata cells and hepatocytes of rats by 4-aminopyrazolo(3,4-d) pyrimidine (4-APP), an inhibitor of the lipoprotein synthesis, are described. Male rats were injected intraperitoneally for three consecutive days with 4-APP in sodium phosphate buffer (50 mg/Kg/day). On the 4th day, the animals were sacrificed and their adrenals and liver were processed for EM. The nucleoli of the adrenal zona fasciculata cells showed nucleolar fragmentation with loss of their normal reticular appearance, separation of fibrillar and granular components, extensive vacuolization and evidence of fibrillar centers. The hepatocyte nucleoli also exhibited fragmentation. These changes seem to be the morphological counterpart of alterations in rRNA synthesis and processing, since 4-APP inhibits “de novo” purine synthesis and thus interferes with its incorporation into RNA and DNA.
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  • 175
    ISSN: 1432-0878
    Keywords: Brain ; Immunohistochemistry ; Natural killer cells ; Monocytes ; Granulocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This study reports a specific cross-reactivity of the three anti-human-hematopoetic-cell monoclonal antibodies, anti-Leu-7 (HNK-1), anti-Leu-11a (NKP-15), and anti-Leu-M1 (MMA), with different epitopes in the brain of the adult rat. The distribution of these epitopes in rat brain is determined by means of immunohistochemistry in paraffin-embedded frontal serial sections. The reaction pattern of anti-Leu-11a monoclonal antibody is very similar to that of polyclonal antibodies against the myelin basic protein. Both antisera give a specific reaction with myelinated fibers. Immunoreaction products with the anti-Leu-7 monoclonal antibody are found as diffuse, mostly punctiform material in the neuropil and even more evident as small granules coating the cell surface of many neurons. In the white matter anti-Leu-7 reveals a moderate reactivity, which occurs predominantly as spots and fine-stranded material within the myelinated fiber tracts. Anti-Leu-M1 immunoreactivity is present between myelinated fiber bundles of the white matter, where it has a reticulate appearance, and as fine-granulated material within the grey matter of the cortex and the nuclei. The characteristic feature in the grey matter is that of irregularly shaped immunopositive plaques, which are often located around small blood vessels. The cytoplasm of glial and neuronal cells appeared negative with this MAB. The exact topographical distribution of the Leu-7 and Leu-M1 epitopes throughout the rat brain is described. The present hypotheses concerning the nature of this shared antigenicity between hematopoetic cells and nervous tissue are discussed.
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  • 176
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    Cell & tissue research 250 (1987), S. 29-33 
    ISSN: 1432-0878
    Keywords: Pituitary gland, pars anterior ; Cysts ; Transplantation ; Differentiation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Hemipituitary glands from 30 rats were isotransplanted under renal capsules. At 1, 2, 4, 7 and 20 days after transplantation, the grafts were examined by light and electron microscopy. Two days after transplantation, the central area of graft showed necrosis; however, the peripheral area, where marginal cells of Rathke's cleft were ingesting the remnants of necrotic glandular cells, survived. Four days after transplantation, mitotic figures of marginal cells were observed. Seven days after transplantation, the damaged area of the graft disappeared, and Rathke's cleft was completely lined by marginal cells. Remnants of necrotic glandular cells were not seen in intercellular spaces or in the cytoplasm of marginal cells. Cystlike structures formed in the grafts; some were connected to Rathke's cleft by narrow cavities. The cavity-lining cells of the cysts were agranular and similar to those that lined Rathke's cleft. At 20 days after transplantation, granular cavity-lining cells appeared. It is suggested that marginal cells of immature rats can differentiate into granular cells.
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  • 177
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    Cell & tissue research 250 (1987), S. 21-27 
    ISSN: 1432-0878
    Keywords: Glomus cell ; Acetylcholinesterase ; Catecholamines ; Carotid body ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The localization of acetylcholinesterase (AChE) was investigated at the cellular and subcellular levels in dissociated cell cultures of the carotid body of the neonatal rat, prepared by the methods of Fishman and Schaffner (1984). In the presence of iso-OMPA, which blocks non-specific cholinesterase, staining was confined almost exclusively to glomus-cell clusters and occasional isolated cells. These clusters grow as discrete islands scattered throughout the culture and display typical catecholamine (CA) fluorescence as in vivo. AChE staining was abolished or reduced by the cholinesterase inhibitors eserine (30–100 μM), or (the poorly lipid soluble) echothiophate (8 (μM). Processing of the same culture sequentially for the demonstration of both AChE and CA revealed that glomus-cell clusters and individual glomus cells were consistently positive for both. In electron micrographs AChE reaction product was associated intracellularly with the nuclear envelope and cytoplasm of glomus cells (identified by their characteristic dense cored granules), as well as extracellularly with the boundaries of contiguous glomus cells. Significantly, reaction product occurred in some glomus cell profiles that had both dense-cored and clear (cholinergic-like) vesicles. These findings are discussed in the context of a possible dual (adrenergic/cholinergic) function status of glomus cells in the rat's carotid body.
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  • 178
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    Cell & tissue research 250 (1987), S. 181-184 
    ISSN: 1432-0878
    Keywords: Prolactin cell ; Secretory granule ; Glycoconjugate ; Lectin ; Concanavalin A ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Prolactin granules in the anterior pituitary glands of male rats contain densely stained materials at the periphery of the matrix. These occur in both small spherical and large polymorphic types of granules. The presence of densely stained materials around secretory granules may be a useful criterion for identification of prolactin cells since the dense structure was observed in 95% of these cells after conventional staining by uranyl acetate and lead citrate. The localization of glycoconjugates in the prolactin granules was examined by applying concanavalin A (Con A) on the ultrathin sections. HRP-Con A or ferritinconjugated Con A bound specifically to the densely stained materials in the peripheral region of the prolactin granule matrix, indicating that this densely stained matrix contains glycoconjugates; the significance thereof is discussed with reference to the concentration and packaging of secretory product.
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  • 179
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    Cell & tissue research 247 (1987), S. 441-444 
    ISSN: 1432-0878
    Keywords: Growth hormone-releasing factor (GRF) ; Neuropeptide immunocytochemistry ; Trigeminal ganglion ; Spinal ganglion ; Development, ontogenetic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Growth hormone-releasing factor (GRF)-like immunoreactivity has been demonstrated in the trigeminal and spinal ganglia of fetal, young and adult rats by use of peroxidase-antiperoxidase immunohistochemistry. GRF-like-immunoreactive cells first appear during the second half of embryonic life, as early as day 17. In untreated animals the GRF-immunoreactive elements form approximately 1% of all ganglion cells in the trigeminal and spinal ganglia; their numbers do not change significantly during development. The granular immunoreaction product is confined to perikarya, especially to the perinuclear region. Nerve fibers displaying GRF-like immunoreactivity were found neither in the ganglia, nor in the corresponding central and peripheral areas of termination. The possible role of GRF in sensory ganglia is discussed.
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  • 180
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    Cell & tissue research 247 (1987), S. 465-468 
    ISSN: 1432-0878
    Keywords: Adenylate cyclase ; Cytochemistry ; Gastrulation ; Ultrastructure ; Chick embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Adenylate cyclase activity was localized in various tissues of the early chick embryo using an ultrastructural histochemical technique. Reaction product was deposited on the lateral plasma membrane of all cells, but with a preferential localization at the apical terminal complex in the epiblast. There was no activity associated with the free surfaces of these or other cells in the embryo. Intracellular deposits were found in all cells associated with the endoplasmic reticulum, nuclear envelope and Golgi bodies. In the last organelle, the deposit was sometimes observed to be distributed through the stack in a non-uniform way, with the heaviest deposits occurring at the forming face. No clear difference could be detected between the cytochemical activity associated with cells in various regions of the embryo, or with embryos at different stages of early development.
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  • 181
    ISSN: 1432-0878
    Keywords: Gonadotropic cells ; LHRH analogue ; Pimo-zide ; Ultrastructure ; Goldfish ; Carassius auratus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effect of pimozide and an LHRH-analogue (LHRH-A) on gonadotropic cells of the goldfish pituitary gland were described qualitatively and quantitatively. A scale of four categories was devised to reflect various ultrastructural appearances of the cells. Experimental animals were divided into a control group, a group injected with LHRH-A alone, pimozide alone, and groups receiving these two substances in combination. Fish injected with the single substance were killed 12 h after injection while the groups receiving the combined treatments were killed at 4, 12 and 48 h. Serum levels of gonadotropin measured by radioimmunoassay were used to indicate whether an increase in hormone release had occurred. An immunocytochemical technique, the protein A-gold procedure, assured that the cells studied were gonadotropes. The control group showed variation in the profiles of gonadotropic cells. The single treatment groups showed some increase in secretory inclusions. At 4 h after injection the combined treatment caused a significant increase in hormone granules; at 12 and 48 h there was a gradual decrease in content of secretory products, and an increase in vacuolization. The results indicate that the combined pimozide and LHRH-A treatment stimulated gonadotropin production as well as release.
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  • 182
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    Cell & tissue research 247 (1987), S. 565-572 
    ISSN: 1432-0878
    Keywords: Synapses ; Perforated synapses ; Synaptic plasticity ; Serial section reconstructions ; Synaptic curvature ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The morphology of perforated synapses in the molecular layer of rat parietal cortex has been studied in 28-day-old animals. Of the perforated synapses analyzed, 92% were axospinous and of these all had asymmetrical contacts. A spinule was present in 20% of them, and 63% had a negative curvature (concave with respect to the presynaptic terminal) overall. Up to 95% of perforated synapses had one or more negatively-curved segments. The perforated synapses studied were characterized by postsynaptic densities (PSD) with a mean length of 581 nm, compared with 233 nm for non-perforated synapses. A study of over 100 serially sectioned synapses demonstrated that, in perforated synapses, the PSD and perforations often had a highly irregular shape and arrangement, the site of the perforation frequently projected into the presynaptic terminal, and coated evaginations of membrane, or coated vesicles, were sometimes found at the site of a perforation or towards the periphery of perforated PSDs. Preliminary reconstructions of perforated synapses suggest that, for descriptive purposes, three types can be recognized. Criteria are formulated for determining, on the basis of a study of single sections, which non-perforated profiles belong to perforated synapses.
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  • 183
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    Cell & tissue research 248 (1987), S. 49-54 
    ISSN: 1432-0878
    Keywords: Enterochromaffin cells ; Serotonin ; Duodenum ; Immunocytochemistry ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Enterochromaffin cells of the rat duodenum have been studied immunocytochemically by use of a specific antiserum to serotonin. At the light-microscopic level serotonin immunoreactivity was observed in enterochromaffin cells located in the epithelium of the duodenal mucosa. Most of the serotonin-immunoreactive material was localized to the basal portion of the enterochromaffin cells, but small amounts of immunoreactive material were regularly observed in the apical portion. At the electron-microscopic level serotonin immunoreactivity in enterochromaffin cells was found to be concentrated over the dense cores of the cytoplasmic granules. The majority of these granules was located in the basal cytoplasm of the enterochromaffin cells, but serotonin-immunoreactive granules were also observed in the apical cytoplasm immediately beneath the microvilli. These observations indicate that duodenal enterochromaffin cells are bipolar and that they secrete serotonin both basally, to the circulation, and apically, to the gut lumen. Rat duodenal enterochromaffin cells thus appear to have an exocrine as well as an endocrine function.
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  • 184
    ISSN: 1432-0878
    Keywords: TRH ; Insulin ; Pancreas ; Streptozotocin ; Regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Streptozotocin treatment at birth induces, in the pancreas of rats, first depletion of insulin and thyrotropin-releasing hormone and then early regeneration ofβ cells and insulin, but not TRH. This study was undertaken to investigate whether the reduction in pancreatic TRH content can be associated with changes in the intensity and the distribution of TRH-immunoreactivity, and to follow the pattern of regeneration ofβ cells through insulin- and TRH-immunoreactivity. In control animals, strong TRH-immunoreactivity was seen in insulin-containing cells on days 1–4 after birth. At day 7, the TRH-immunoreactivity was already decreased. In contrast, insulin-immunoreactivity was present throughout the neonatal period. A sparse population of cells near ducts also contained both TRH- and insulin-immunoreactivity at 1–2 days age. In streptozotocin-treated animals, TRH-immunoreactivity is found only in a few scattered insulin-containing cells in altered islets on days 1–4. Near the ducts, there were new insulin-containing cells which did not contain TRH. From day 7 regeneration of endocrine cells was characterized by new, typical islets, but these contained insulin-, but not TRH-immunoreactivity. These findings suggest a differential control of the biosynthesis of insulin and TRH within the pancreas.
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  • 185
    ISSN: 1432-0878
    Keywords: Neuromuscular synapse ; Lectin histochemistry ; Dolichusbiflorus agglutinin ; Synaptogenesis ; Denervation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The binding of agglutinin fromDolichus biflorus (DBA) and other lectins (Concanavalin A, agglutinin from wheat germ and lectin fromBandeiraea simplicifolid) to synaptic and extrasynaptic portions of the basal lamina of muscle fibers, was studied with histochemical methods. In rat muscle, DBA-binding is specifically detected at the basal lamina of neuromuscular junction. However, long-term (6 months) denervated end-plate in adult rat muscle failed to bind DBA. During normal development, synaptic DBA receptors appear later than acetylcholine receptors or acetylcholinesterase at the rat neuromuscular junction. Generalized DBA-binding to motor end-plates is first visualized in 3-day-old rats, but section of sciatic nerve in 1-day-old rats prevents the appearence of synaptic DBA-binding on the leg end-plates. It is suggested, therefore, that the synaptic DBA receptors could be related to the postnatal stabilization of rat neuromuscular synapses.
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  • 186
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    Cell & tissue research 248 (1987), S. 699-702 
    ISSN: 1432-0878
    Keywords: Albumin ; Ovarian follicles ; Granulosa cells ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The purpose of this study was to investigate whether albumin (Alb) can be detected in ovarian rat granulosa cells. Using immunocytochemistry and morphometrics, the percentages of Alb-positive follicles (follicle-index), of Alb-positive granulosa cells (granulosa-index), and of strongly reacting follicles (intensity-index) were evaluated in intact and regressing follicles of different diameter groups during different stages of the estrous cycle. In intact follicles, the follicle- and the granulosa-index increased from small-sized to large-sized follicles. Although the follicle-index did not change in any group during the stages of the estrous cycle, the granulosa-index was higher during proestrus than during the other stages. Intact follicles showed a stronger immunoreactivity than regressing follicles throughout the stages of the estrous cycle. Thus, Alb may be a requirement for the control of follicle growth in fertile rats. This Alb function may be attributable to Alb binding to specific cell-membrane components followed by the intracellular uptake of Alb-bound substances.
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  • 187
    ISSN: 1432-0878
    Keywords: Endolymphatic sac ; Calcium carbonate ; Otoconia ; Ultrastructure ; Frog (Hyla arborea japonica)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The endolymphatic sac of the tree frog and its crystals were observed by light- and electron microscopy. Scanning electron microscopy revealed that the crystals have a faceted body and two pointed ends. Light- and transmission electron microscopy revealed that the endolymphatic sac is composed of many small chambers. In their lumina, numerous “ghosts” of crystals that resulted from decalcification were observed. The ghosts were demarcated by a linear dense material or embedded in a flocculent substance. The epithelium of the endolymphatic sac is simple squamous or cuboidal and peculiar cytoplasmic granules are found in most cells. The granules are surrounded by a limiting membrane and have varying electron density. Some granules contain a core and/or tubular structures. Vacuoles containing large ghosts are also found in the epithelial cells. These ghosts were quite similar to those in the lumen and sometimes coexist with cell debris. The fine structure of the endolymphatic sac and its crystals is discussed.
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  • 188
    ISSN: 1432-0878
    Keywords: Epididymis ; Immunogold technique ; Ultrastructure ; Protein secretion ; Antagglutinin ; Boar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Antagglutinin, a specific protein synthesized by the boar epididymis, was localized by an ultrastructural immunogold-labeling procedure in the principal cells of the three regions of the caput epididymidis, most notably at the sites of synthesis and secretion. The intensity of the reaction was variable in the three epididymal zones. Labeling was of low intensity in the proximal and middle caput, except in the granules of the latter. These granular “storage sites” did not correspond to typical secretory granules but appeared to be intracellular sites of degradation of this protein. In the distal caput, which was devoid of these granules, intense secretory activity for antagglutinin was detected. Few gold particles were localized in the RER profiles but labeling was detected in the Golgi zone, in numerous dense vesicles, in structures distributed between the Golgi zone and the apex of the cell, and in the epididymal lumen. This study has enabled us to visualize immunocytochemically antagglutinin along its intracellular secretory pathway, i.e. at the site of its synthesis, during its passage via the Golgi zone, and its intracellular transport to the lumen.
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  • 189
    ISSN: 1432-0878
    Keywords: Androgen ; Estrogen ; Pituitary ; Autoradiography ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Castrated male and female rats pretreated with dihydrotestosterone (DHT) were injected i.v. with 3H-estradiol (E2). Nuclear uptake and retention of 3H-E2 was measured in each of five cell types of the anterior pituitary gland using a combined quantitative autoradiographic and immunocytochemical procedure. In non-pretreated groups, each cell type bound a characteristic amount of ligand but no sex differences were apparent. DHT pretreatment, however, caused a significant decrease in 3H-E2 retention by gonadotrophs in both males and females. The treatment also caused a decrease in binding by lactotrophs and somatotrophs, but only in the females. No other cell types were altered. Thus, androgen appears to modulate E2 binding and retention by pituitary cells in both a cell-type and sexdependent manner. Our results also indicate that the inhibitory effects of androgens on E2 binding by the pituitary gland is more complex than can be explained by simple competition for the estrogen receptor.
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  • 190
    ISSN: 1432-0878
    Keywords: Lectin histochemistry ; Transport epithelia Immunolocalization: (Na++K+)-ATPase, carbonic anhydrase ; Kidney collecting ducts ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To identify precisely the structural and functional cell type in the collecting duct of the rat kidney expressing binding sites for Dolichos biflorus agglutinin (DBA), we stained serial paraffin sections of kidney with horseradish peroxidase-labeled DBA and with immunocytochemical methods for localizing (Na++K+)-ATPase and carbonic anhydrase II (CA II), enzymes found preferentially in principal and intercalated cells, respectively. Most principal cells expressing a strong basolateral staining for (Na+ + K+)-ATPase showed binding sites for DBA at their luminal surfaces. However, a minority of cells rich in CA II and showing morphologic characteristics of intercalated cells also expressed DBA binding sites at their luminal surface and apical cytoplasm. These data suggest that DBA cytochemistrycan provide a useful tool for studying the functional polarity of the main cell types of the collecting duct of the rat kidney.
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  • 191
    ISSN: 1432-0878
    Keywords: Immuno-electron microscopy ; Triple-immunogold-labeling ; CRF axon terminal ; Median eminence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructural appearances of axonal terminals containing corticoliberin (CRF) were examined in the rat median eminence prepared by a freeze-drying procedure. Immunolabeling was performed by using 5-, 8-, or 15-nm gold-antibody complexes for CRF, arginine vasopressin (VP) and methionine-enkephalin-octapeptide (Enk-8), singly or in combination. In intact animals, the CRF-containing secretory granules were only slightly labeled with goldanti-VP or -Enk-8. In adrenalectomized rats, granules within single axons appeared to be labeled with all the immunogold complexes. This intragranular colocalization of the three antigens was confirmed by using three neighboring sections of the same axon terminals which were stained separately with each one of the antibodies and visualized with the avidin-biotin-peroxidase complex method. The granules labeled for CRF had decreased 9 days after adrenalectomy but had increased again by day 21, while those labeled for VP steadily increased after adrenalectomy. However, this did not correspond with the appearances of cell bodies in the paraventricular nucleus; the cell bodies labeled for both CRF and VP steadily increased in number and in stainability. By contrast, Enk-8 immunoreactivity in the axonal terminals and cell bodies was not affected by adrenalectomy. These findings suggest that although the three peptides could be released simultaneously from the axonal terminals, VP may play some special role in the expression of CRF activity.
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  • 192
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    Cell & tissue research 249 (1987), S. 577-586 
    ISSN: 1432-0878
    Keywords: Parotid gland ; Duct cells ; Ferritin ; Endocytosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ability of the intralobular ducts of the rat parotid gland to take up protein from the lumen was examined after retrograde infusion of native and cationized ferritin. At high concentrations (3–10 mg/ml), cells of both intercalated- and striated ducts avidly internalized the tracers. No differences were noted in the mode of uptake or fate of native or cationized ferritin. Large, apical ferritin-containing vacuoles up to 5 μm in size were present in cells of the intercalated ducts after infusion for 15 min. Small, smooth-surfaced spherical or flattened vesicles and tubules containing ferritin were also observed, often in association with the large vacuoles. Ferritin uptake increased with increasing infusion time, up to 1 h. Uptake by the striated ducts was less consistent than by the intercalated ducts, and occurred mainly in small vesicles and tubules. Secondary lysosomes became labeled with ferritin in both cell types. Ferritin was not observed in the Golgi saccules, nor was it discharged from the cells at the basolateral surfaces. At low concentrations (0.3–1 mg/ml), uptake was reduced, especially by cells of intercalated ducts, and differences were noted in the behavior of the two tracers. Cationized ferritin was internalized mainly into vesicles and tubules of cells of striated ducts; little uptake of native ferritin occurred at low concentrations. These results demonstrate that the ductal cells of the salivary glands are capable of luminal endocytosis of foreign proteins. They also suggest that in addition to modifying the primary saliva by electrolyte reabsorption and secretion, and secretion of various glycoproteins, the ductal cells are able to reabsorb proteins secreted by the acinar cells.
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  • 193
    ISSN: 1432-0878
    Keywords: γ-Aminobutyric acid (GABA) ; Autoradiography ; Development, ontogenetic ; Duodenum ; Uptake sites ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The localization of high-affinity uptake sites for 3Hγ-aminobutyric acid (3H-GABA) was investigated in the rat duodenum during ontogenesis and also at the adult stage (from 15.5 days of fetal life up to 105 days post natum) by means of low- and high-resolution autoradiography. At all stages studied, specific endocrine cell types of the epithelium were labelled and an intense uptake was detected in the nervous tissue, especially in glial cells but also in scarce neurones. When the incubation medium was supplemented with β-alanine (1 mM), a blocker of the glial uptake for GABA, the labelling persisted only in endocrine cells and in few neurones. The intensity and the frequency of the labelling decreased at later periods compared to the earlier developmental stages. The GABA content of the duodenum as measured by a new ion-exchange column chromatography-HPLC-coupled method was higher in the early postnatal period compared to later stages. These observations suggest that GABA, in addition to being a neurotransmitter, may play an important role during development of the duodenum.
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  • 194
    ISSN: 1432-0878
    Keywords: 7B2 polypeptide ; Gastro-intestinal tract ; Endocrine cells ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunoreactivity to the polypeptide designated “7B2” recently isolated from human and porcine pituitary glands, appears to be consistently confined to neuroendocrine and endocrine cells in various tissues. In rat gut, immunoreactive 7B2 was found in endocrine-paracrine cells. Highly labeled cells were found in the antrum of the stomach and, cells with lower concentrations, in the fundus, duodenum, jejunum and ileum. Except for a few cells which were simultaneously positive for 5-hydroxytryptamine, and a few others showing Grimelius's reaction, “7B2” cells do not exhibit argentaffin and/or argyrophil character. The 7B2 polypeptide seems to be distributed amongst several different types of endocrine cells in the gut.
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  • 195
    ISSN: 1432-0878
    Keywords: Organum vasculosum laminae terminalis (OVLT) ; Capillaries ; Horseradish peroxidase ; Leptomeninges ; Blood-blood barrier ; Blood-cerebrospinal fluid barrier ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using intravenously injected horseradish peroxidase (HRP) as tracer, we demonstrate, that — in contrast to other neurohemal regions — the organum vasculosum laminae terminalis (OVLT) is composed of two functionally different divisions. Both parts of the OVLT are endowed with fenestrated capillaries which, however, obviously differ in their permeability for HRP. In one of these portions the neurohemal region remains unlabeled under the experimental conditions used, while the other portion, in analogy to the majority of neurohemal regions, is labeled by the tracer. The functionally different divisions of the OVLT are separated from one another by tanycytic processes and meningeal cells establishing a barrier between the two hemal compartments. The meningeal elements penetrate the organ in the form of an uninterrupted layer; they are continuous with the pia mater and produce large amounts of basal lamina-like material. Furthermore, they provide the delineation of the OVLT against the outer cerebrospinal fluid-containing compartment, a structural feature that is characteristic of both divisions of the OVLT and corresponds to the arrangement of meninges in all other portions of the brain where a blood vessel penetrates its surface.
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  • 196
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    Cell & tissue research 250 (1987), S. 641-648 
    ISSN: 1432-0878
    Keywords: Kidney ; Interstitial cells ; Lysosomes ; Sulfated glycosaminoglycans ; Tilorone ; Mucopolysaccharidosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This investigation provides histochemical evidence for lysosomal storage of sulfated glycosaminoglycans (GAGs) in the interstitial cells of the renal cortex and in macrophage-like cells of the renal medullary zones of rats chronically treated with the drug tilorone. This compound is known to interfere with lysosomal degradation of sulfated GAGs; therefore cells that develop GAG-storage can be assumed to be involved in the turnover of GAGs. In view of this consideration, the most remarkable and still unexplained finding was that the intrinsic interstitial cells in the papilla, which is known to be particularly rich in sulfated GAGs, did not show the cytological symptoms of lysosomal GAG-storage. The present findings may stimulate further studies focused on the cellular sites of turnover of the sulfated GAGs present in the renal medullary interstitium.
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  • 197
    ISSN: 1432-0878
    Keywords: Myocyte subpopulations ; Hypertension ; Cell volume ; Doubling time ; Tetraploid cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Smooth muscle cells obtained from three distinct segments of the thoracic aorta of both Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR) taken at different stages of development were studied in terms of their volume, DNA content in single cell suspensions, and doubling time in primary cultures. The proliferative activity and mean cell volume of myocytes from WKY rats increase along the thoracic aorta in a gradient from the aortic arch to the diaphragm. The slope of this gradient is increased in SHR because of an extension of the area that contains myocytes with low proliferative activity in primary cell culture and large cell volumes in suspension. Tetraploid myocytes are found in both strains and their proportions are larger in SHR than in WKY, specifically after the onset of hypertension. However, they appear to be evenly distributed along the thoracic aorta with a size distribution that is included in that of the diploid cells from the same area. It is suggested that changes in the structural properties of the aortic-cell compartment, associated with maturation and hypertension, reflect quantitative changes in the relative proportions of several myocyte subpopulations within the aorta of the rat.
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  • 198
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    Cell & tissue research 247 (1987), S. 215-225 
    ISSN: 1432-0878
    Keywords: Kidney ; Endoplasmic reticulum ; Ultrastructure ; Membrane transport ; Metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The spatial organization of endoplasmic reticulum (ER) was examined in all segments of rat nephron. Tissues were fixed with glutaraldehyde, impregnated “en bloc” with osmium tetroxide, prepared for and examined by standard (80–100 kV) and high voltage (1 mEV) transmission electron microscopy. In all proximal tubule cells, ER forms a continuous and extensive network of canaliculi and abundant fenestrated saccules which surround mitochondria and cytoplasmic bodies; the cage-like structure of the fenestrated saccules was most evident around the spherical mitochondria of the S3 segment. In the cells of the distal straight and convoluted tubules, the network consists mostly of canaliculi with rare non-fenestrated saccules. The ER network of canaliculi is particularly rich in intercalated cells, in contrast with its rudimentary appearance in the adjacent principal cells of the collecting tubule. In fact, in these cells there are few isolated ER cisternae and they are rarely impregnated. The nuclear envelope is well impregnated in most cells throughout the various segments. Segmental variations in ER organization and its relative abundance are most likely related to the well, established functional heterogeneity of the nephron segments. Moreover, the extensive and unique organization among mitochondria, ER and the basolateral membrane suggests that these three organelles function as a unit which is related to active electrolyte transport. In addition, because of its transepithelial organization, ER may well constitute a transcellular pathway for molecules.
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  • 199
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    Cell & tissue research 247 (1987), S. 241-247 
    ISSN: 1432-0878
    Keywords: Somatomedin C ; Insulin-like growth factor I (IGF-I) ; Axoplasmic transport ; Sciatic nerve ; Schwann cell ; Trophic influence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Somatomedin C (Sm-C; insulin-like growth factor I; IGF-I) is a polypeptide (Mr 7649), often dependent on growth hormone (GH), with trophic effects on several different tissues. Monospecific IGF-I antisera were used to investigate its localization in the sciatic nerve and corresponding nerve cells, as well as its possible axoplasmic transport in the adult rat. IGF-I-like immunoreactivity was demonstrated in anterior horn motor nerve cells in the spinal cord and in spinal- and autonomic ganglion nerve cells. Faint IGF-I immunoreactivity was under normal conditions observed in axons of the sciatic nerve and in the Schwann cells. Using crush technique, accumulation of IGF-I immunoreactivity was seen in dilated axons within 2 h, both proximal and distal to the crush. However, only a small fraction of the anterogradely transported IGF-I immunoreactive material could be demonstrated to be transported in retrograde direction. Colchicine injected proximal to a crush prevented accumulation of IGF-I immunoreactivity proximal to the crush, but not distal to it. IGF-I-immunoreactive material is synthesized in the cell bodies of peripheral sensory and motor nerve cells. It is transported at rapid rates in the axoplasm of the sciatic nerve of adult rats both in anterograde and retrograde directions. We propose that axonally transported IGF-I may be released and exert trophic influence on innervated cells, tissues and organs.
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  • 200
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    Cell & tissue research 247 (1987), S. 259-265 
    ISSN: 1432-0878
    Keywords: Epidermis ; Acidophilic cell ; Histochemistry ; Ultrastructure ; Salmo trutta ; Salvelinus alpinus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Sacciform cells containing an acidophilic, proteinaceous secretion, were identified in the epidermis of the brown trout and Arctic char. This cell type increased in number during the chronic stages of infestation by the ectoparasitic flagellate, Ichthyobodo sp., in immature brown trout, and decreased during sexual maturation in male brown trout and char. It is suggested that the salmonid sacciform cell produces a secretion which protects the fish against infestation or damage by skin parasites.
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