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  • 1985-1989  (305)
  • 1870-1879
  • 1985  (305)
  • Rat  (203)
  • Ultrastructure  (112)
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 58 (1985), S. 183-189 
    ISSN: 1432-1106
    Keywords: Olivocerebellar projection ; Axonal branching ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Axonal branching in the olivocerebellar projection was investigated using the retrograde fluorescent double-labelling method. Combinations of true blue and diamidino yellow injections (50 nl) were made in the cerebellar cortex of anaesthetized rats to investigate branching within single longitudinal zones and branching between such zones. The topographical arrangement of the projection was similar to that previously described, but additionally it was found that lateral parts of the inferior olive project more rostrally within a longitudinal zone and medial parts project more caudally in the same zone. Double-labelled olivary neurones, with axons branching rostrally and caudally within a single zone, were found to lie in an intermediate position between the two groups of single-labelled neurones. No such double-labelled neurones occurred when branching between zones was investigated. The correlation between these anatomical findings and earlier physiological work is discussed.
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  • 102
    ISSN: 1432-1106
    Keywords: Antidromic activation ; Latency variation ; Axonal excitability ; Paraventricular nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Magnocellular neurosecretory cells were antidromically identified in the hypothalamic paraventricular nucleus (PVN) of urethane-anesthetized, ovariectomized female rats following electrical stimulation of the neurohypophysis. Seventy-one cells with a tonic pattern of spontaneous discharge were distinguished and used to examine the relationships between the measures of antidromic spike latency, activation threshold and discharge rate. The discharge rate was artificially modulated by either microiontophoresis of glutamate or antidromic stimulation of the neurohypophysis. In all the PVN cells with tonic activity, the latency lengthened and the threshold increased as a function of the discharge rate. Activation of individual cells by microiontophoresis of glutamate was effective, as was simultaneous activation of many PVN cells by antidromic stimulus. Similar relationships between the discharge rate and the parameters of antidromic activation were seen in 3 cells, when their rates varied spontaneously over a wide range without manipulation. These data suggest that the excitability of axons of presumed oxytocinergic cells in the PVN-neurohypophyseal system are influenced by their prior activity, probably through metabolic changes in individual axons.
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  • 103
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    Experimental brain research 60 (1985), S. 318-322 
    ISSN: 1432-1106
    Keywords: Gustation ; Taste ; Electric taste ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cathodal OFF response in electric taste, the production of a taste sensation at the break of a microampere cathodal current passed through the tongue, was studied electrophysiologically in the rat chorda tympani nerve. Previous work in electric taste has centered on ON responses to both anodal and cathodal currents. The cathodal OFF response, like ON responses, increased with increasing current intensity until a saturated response level was achieved. Unlike previously reported ON responses, the OFF response did not show a sensitivity to the ionic composition of the fluid bathing the tongue making this the first electrophysiological report of ion insensitivity in electric taste. The cathodal OFF response was sensitive to the duration of the current pulse preceding it. Longer pulses produced larger OFF responses, until with very long pulses (seconds) a saturated response level was achieved. The half maximal response occurred at 12.5 ms. These results have been interpreted to mean that the cathodal OFF response has an origin other than the microvillus membrane, the site most often implied for ON responses, due largely to its ion insensitivity. A probable location may reside with ion channels transversing the basal membrane which are transiently excited at the break of the current resulting in excitation at the receptor-afferent synapse.
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  • 104
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    Experimental brain research 60 (1985), S. 501-508 
    ISSN: 1432-1106
    Keywords: Medial terminal accessory optic nucleus ; Rat ; Rabbit and cat ; Neuron morphology ; Dendritic architecture ; Golgi impregnation methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neurons of the medial terminal nucleus (MTN) of the accessory optic system (AOS) have been studied in the rat, rabbit and cat in Golgi-Cox and Golgi-Kopsch impregnated brain sections. The present anatomical findings permit a division of the MTN of these species into dorsal and ventral components (MTNd, MTNv), in agreement with other investigations. The MTNd contains predominantly linear-bipolar and linear-multipolar shaped neurons with cell bodies that measure in the range of 25–50 μm. These neurons have 2 to 4 primary dendrites which, along with their smaller dendritic branches, are oriented in the plane of the long axis of the MTN (i.e. from ventromedial to dorsolateral). These linear-bipolar and linear-multipolar cells represent 70–80% of the neurons of the MTNd as seen in the Golgi impregnated sections. The remaining 20–30% of the MTNd neurons are nearly all multipolar in shape with somata measuring in the range of 15–25 μm. An occasional multipolar neuron is larger, has a soma that measures around 30–60 μm and has dendrites which extend outward from the cell body to cover large areas of the MTNd. There was considerable extension of the dendrites of MTNd neurons into the MTNv; however, the dendrites of MTNd neurons were not observed extending into the adjacent substantia nigra (SN) or ventral tegmental area (VTA) of Tsai (1925). Conversely, the dendrites of neurons in the neighboring SN and VTA course along the borders of the MTN but only occasionally extend into the MTN. The neuron population of the MTNv consists almost entirely of small-multipolar shaped cells with somata measuring from 15–25 μm and dendritic trees resembling those described for multipolar cells of the MTNd. A small number of neurons of the ventral division are medium-multipolar in shape with cell bodies that measure approximately 30–60 μm. Typically, these cells have several dendrites which extend ventrally within the MTNv and one or more dendrites that extend either across the MTNv or dorsally into the MTNd. Only a few linear-bipolar and linear-multipolar neurons were observed in the MTNv. The present findings are discussed in relation to anatomical, physiological, and histochemical studies on the MTN.
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  • 105
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    Experimental brain research 60 (1985), S. 564-575 
    ISSN: 1432-1106
    Keywords: Dorsal lateral geniculate nucleus ; Lateroposterior thalamic nucleus ; Superior colliculus ; Microphthalmia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tecto-thalamic projections in the hereditary bilaterally microphthalmic rat were studied by means of WGA-HRP injection into the dorsal lateral geniculate nucleus (LGNd) and the lateroposterior thalamic nucleus (LP). Histological study in the mutant rats showed that whereas LGNd and superficial layers of the superior colliculus (SC) suffered from a remarkable reduction in size, LP had no histological changes as compared to the normal animals. Unilateral injection of the tracer into the microphthalmic LGNd showed that WGA-HRP positive neurons were present mostly in the ipsilateral str. griseum superficiale (SGS) of the SC. However, the number of labeled SGS neurons of the microphthalmic animals was about 3% of the normal. Although cell bodies of the normal tecto-LGNd neurons in the SGS were spindle-form in shape and issued one or two proximal dendrites from each pole, the microphthalmic tecto-LGNd neurons showed an irregular contour and their dendrites were not so intensively labeled. Unilateral injections of WGA-HRP into the LP revealed that the tecto-LP neurons were mainly distributed in the ipsilateral str. opticum of the colliculus. (SO) in both normal and microphthalmic animals. However, the number of labeled SO cells in the microphthalmic rat was about one-half of the normal. Furthermore, the size of labeled tecto-LP neurons was smaller than that of the normal ones, and they showed irregular round to oval cell bodies with equivocally labeled dendrites, in contrast to the normal tecto-LP neurons with polygonal cell bodies extending three or more dendrites in a radial fashion. These results indicate that there exist the tecto-LGNd and -LP projection neurons in the microphthalmic rat and that their laminally segregated projection is fundamentally preserved. However, the number of the tecto-thalamic projection neurons, especially of the tecto-LGNd cells, was markedly diminished in the mutant tectum compared to normals.
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  • 106
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    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 354-357 
    ISSN: 1432-1912
    Keywords: Autoradiography ; β-Adrenoceptor subtypes ; Kidney ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present autoradiographical study examines the distribution of the two β-adrenoceptor subtypes in sections of rat and guinea-pig kidney. The radioligand [125Iodo]-(-)-cyanopindolol was used for the labelling of β-adrenoceptors and the selective β-adrenoceptor blocking agents ICI 89-406 (β1-antagonist) and ICI 118-551 (β2-antagonist) were utilized to differentiate both subclasses unequivocally. β-Adrenoceptors in rat kidney were found to be almost exclusively β1. They were located mainly on glomeruli and to a lesser extent on the straight part of the distal tubules and on the cortical portion of the collecting ducts. Some β2-adrenoceptors were localized around the corticomedullary junction. Grain localization in the autoradiograms was absent in the inner medulla and papilla. Glomeruli and distal tubules of the guinea-pig kidney also possess only β1-adrenoceptors, but, in contrast to the rat, extremely high concentrations of β2-adrenoceptors were associated with the straight part of the proximal tubules in the cortex and possibly with the cortical portion of the collecting duct. Labelling was not detected on the proximal convoluted tubule in either species.
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  • 107
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    Naunyn-Schmiedeberg's archives of pharmacology 331 (1985), S. 225-234 
    ISSN: 1432-1912
    Keywords: γ-Aminobutyric acid (GABA) ; Noradrenaline turnover ; Locus coeruleus ; Impulse flow ; GABA mimetics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to explore the nature of the facilitatory GABAergic control of cerebral noradrenergic neurons, we have studied the effect of a variety of GABA mimetics (given systemically or injected locally into brain areas containing noradrenergic cell bodies or terminals) on several indices of noradrenaline turnover in the rat brain. Systemic administration of both direct and indirect acting GABA mimetics enhanced; 1) the pargyline induced accumulation of normetanephrine in the hypothalamus; 2) total DOPEG levels in a number of brain regions innervated by noradrenergic neurons; 3) both DOPAC and MOPEG levels in noradrenergic cell body areas (A1, A2 and A6). These effects are probably mediated by GABAA receptors as specific GABAA or mixed GABAA/GABAB agonists but not the GABAB agonist baclofen enhanced noradrenaline turnover. Interruption of noradrenergic impulse flow (by local injection of tetrodotoxin or by hemitransection) blocked the ability of progabide to increase DOPEG concentrations in the hypothalamus and cerebral cortex. Similarly, the coadministration of clonidine with progabide antagonized the progabide-induced increase in hypothalamic total DOPEG levels. Co-administration of yohimbine with progabide provoked an additive effect on hypothalamic DOPEG levels at moderate but not at high doses of yohimbine. Thus, the acceleration of noradrenaline turnover induced by GABA mimetics appears to depend on ongoing activity in noradrenergic neurons and occurs via an increase in neuronal discharges. Local injection of muscimol into the nucleus accumbens or hypothalamus failed to affect DOPEG levels in these structures; similarly, local injection of muscimol into the locus coeruleus failed to modify DOPEG levels in corresponding noradrenergic projection areas. These data indicate that the GABAergic influence is not exerted via GABA receptors located on noradrenergic cell bodies or nerve endings. Furthermore, since systemically administered progabide still increased hypothalamic DOPEG levels after ibotenate-induced destruction of the hypothalamic neuronal cell bodies, a presynaptic modulation of noradrenergic neurons by local GABAergic interneurons is excluded. Chemical desctruction of serotoninergic pathways or enhancement of 5-HT transmission by quipazine failed to alter the ability of progabide to increase cerebral DOPEG levels. Moreover, seopolamine or naloxone also failed to affect the progabide-induced increase in cerebral DOPEG levels. These results exclude the implication of serotoninergic, cholinergic and opioid systems in the mediation of the facilitatory influence of GABA on noradrenergic neurons. It is concluded that the facilitatory GABAergic influence on cerebral noradrenergic transmission is probably indirect and mediated via GABAergic synapses involved in transsynaptic neuronal circuits (the nature of which remains to be defined) regulating noradrenergic cell activity.
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  • 108
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    Psychopharmacology 87 (1985), S. 292-297 
    ISSN: 1432-2072
    Keywords: Brain syndrome ; Cerebral ventricles ; Intraventricular injection ; Rat ; Psychosis ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new experimental brain syndrome involving localized periventricular damage induced by intracerebroventricular injections of lysophosphatidyl choline has been developed in adult rats. The acute periventricular injury syndrome is characterized by transient weight loss, decreased emotionality, extreme postural indifference (catalepsy), inappropriate aggressive responses, impaired grooming, cerebral ventricular enlargement, and periventricular damage to both cells and fiber sheaths. This syndrome appears to simulate several features of schizophrenia, and it may prove useful in the study of psychotic disorders in man.
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  • 109
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    Psychopharmacology 86 (1985), S. 147-152 
    ISSN: 1432-2072
    Keywords: Benzodizepines ; Indalpine ; Zimelidine ; Serotonergic neurons ; Waiting capacity ; Impulse control ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated whether benzodiazepines reduce the capacity of animals to wait for food reward. Rats trained in a T-maze were allowed to choose between two magnitudes of reward: immediate, but small (two pellets) vs delayed, but large (eight pellets). The rats learned within ten sessions to select (80–100%) the arm leading to the largest reward. Separate groups of rats were then confined for 15, 30 or 60 s in the arm associated with the largest reward before gaining access to the spacially contiguous goal-box. The choice of the other arm was not followed by a period of waiting. Under these conditions, the frequency with which the small-reward arm was chosen increased linearly as a function of the duration of the waiting period. Diazepam (2–4 mg/kg IP) dose-dependently increased the number of times the small-reward arm was chosen during the sessions for which the waiting period was fixed at 15 or 30 s. Nitrazepam (2 mg/kg IP), chlordiazepoxide (16 mg/kg IP) and clobazam (16 mg/kg IP) had similar effects. The action of diazepam was counteracted by simultaneous administration of flumazepil (Ro 15-1788, 8 mg/kg PO). In the absence of confinement, these benzodiazepines, diazepam (4 mg/kg) excepted, did not modify selection of the large-reward arm. Conversely, the serotonin uptake blockers indalpine (2–4 mg/kg IP) and zimelidine (8–16 mg/kg IP) dose-dependently increased preference for the arm leading to the delayed (25 s) but large reward. These results suggest that benzodiazepines, perhaps by increasing impulsivity, render the animals less prone than controls to tolerate delayed access to reward. It is hypothesized that serotonergic neurons play a crucial role in impulse control and in the benzodiazepines-induced shift towards the immediate reward.
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  • 110
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    Psychopharmacology 86 (1985), S. 318-323 
    ISSN: 1432-2072
    Keywords: dl-Amphetamine ; Continuous reinforcement ; Partial reinforcement ; Resistance to extinction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of amphetamine administration on the partial reinforcement extinction effect (PREE) at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested inextinction. dl-Amphetamine 1.5 mg/kg was administered in a 2×2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction. In contrast, amphetamine administered in acquisition abolished the PREE irrespective of drug treatment in extinction. In addition, amphetamine administered in extinction alone increased resistance to extinction in PRF animals.
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  • 111
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    Psychopharmacology 86 (1985), S. 68-76 
    ISSN: 1432-2072
    Keywords: Maternal aggression ; Female aggression ; Offense ; Defense ; Ethopharmacology ; Fluprazine ; Chlordiazepoxide ; Serenics ; Benzodiazepines ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although maternal agression in rats is confined to a restricted post-partum period, the high and stable aggression level and the constancy of its behavioural structure make it an attractive experimental procedure for studying the behavioural effects of psychotropic drugs. Female rats were tested against naive male intruder rats for 5 or 10 min on post-partum days 3–9, during which aggression is stable. Chlordiazepoxide (CDP; 5, 10 and 20 mg/kg, orally) had a biphasic effect on aggression; it increased aggression considerably at 5 and (to a lesser extent) at 10 mg/kg. At 20 mg/kg aggression returned to control level. CDP shortened the latency to the first attack at 5 mg/kg, but not at higher dosages. CDP enhanced aggression, particularly in the first 2 min of an encounter. It did not change the structure of the aggressive behaviour, but did induce a dosedependent increase in feeding. Fluprazine (Flu; 5, 10 and 20 mg/kg IP), a specific antiaggressive (serenic) drug, induced a dose-dependent decrease in aggression and exerted its largest effect in the first 2 min of an encounter. In accordance with the reduced aggression, latencies to the first attack increased. Maternal aggression in rats represents an extension to other (male) aggression paradigms in psychopharmacology. First, it has no male counterpart. Secondly, the hormonal mechanisms underlying this behaviour differ from those of male aggression. Thirdly, the morphology of maternal aggression is different from that shown in male models of agonistic behaviour (e.g. resident-intruder). These features make maternal aggression an attractive paradigm for pharmacological studies of female behaviour.
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  • 112
    ISSN: 1432-2072
    Keywords: 5-HT ; p-Chloroamphetamine ; Zimeldine ; p-Chlorophenylalanine ; Active avoidance ; Acquisition ; Nociception ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p-Chloramphetamine (PCA, 0.63–5 mg/kg IP) injected 30–60 min before testing produced a dose-related impairment of avoidance acquisition, prolonged reaction time in the hot-plate test and increased locomotor activity. Pretreatment with the selective serotonin (5-HT) uptake inhibitor zimeldine (10 mg/kg IP) blocked these behavioural effects. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2×10 mg/kg IP) or inhibition of tryptophan hydroxylase by p-chlorophenylalanine (300 mg/kg IP) also blocked the behavioural effects of PCA. There was a complete blockade of the PCA-induced avoidance deficit following pretreatment with metergoline, a central 5-HT receptor blocking agent. On the other hand, metergoline failed to block the hot-plate analgesia and the increased locomotion caused by PCA. Depletion of brain NA and DA by the tyrosine hydroxylase inhibitor H44/68 did not counteract the PCA effect on avoidance or hot-plate performance, but reduced the locomotor stimulating effect. The selective NA neurotoxin DSP4 (50 mg/kg IP) or the opiate antagonist naloxone (1 mg/kg) failed to affect the PCA-induced modulations of the behaviours studied. In addition, PCA administration in doses that caused avoidance deficits, did not result in motor impairment as assessed by the tread mill test. The above results support the hypothesis that the PCA-induced impairment of active avoidance acquisition does not involve changes in nociception or altered locomotor activity. It is concluded that behavioural processes related to serotonergic neurotransmission can be independently modified, suggesting differences in the underlying 5-HT mechanisms.
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  • 113
    ISSN: 1432-2072
    Keywords: Conditioned place preference ; Aversions ; Naloxone ; Morphine ; U50-488 ; β-endorphin ; Dynorphin ; Arcuate nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examines the influence of destruction of the medio-basal arcuate hypothalamus (MBH), the primary site of synthesis of central pools of β-endorphin (β-EP), upon the aversive properties of naloxone in a conditioned place preference paradigm. Bilateral radiofrequency lesions of the MBH resulted in a pronounced fall in levels of immunoreactive β-EP in the brain. Lesioned rats, in contrast to non-operated animals, showed a clear reduction in the conditioned place aversion produced by naloxone. However, they showed no loss of the conditioned preference produced by the mu-selective opioid receptor agonist, morphine, or the conditioned aversion produced by the kappaselective agonist, U50-488. In contrast to the effect of the lesions, suppression of circulating β-EP by dexamethasone treatment failed to influence conditioning produced by naloxone. Thus, the data indicate that the aversive properties of naloxone are attenuated by disruption of central (but not peripheral) β-EP activity. We suggest that these properties of naloxone reflect an antagonism of β-EP activity in the brain. In addition, the data indicate that differing mechanisms underlie the aversive actions of naloxone as compared to U50-488.
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  • 114
    ISSN: 1432-2072
    Keywords: GABAergic hypothesis of anxiolytic action ; Muscimol ; Baclofen ; Chlordiazepoxide ; Picrotoxin ; Bicuculline ; Spontaneous alternation ; Response to stimulus change ; Exploration ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two methods were used to test rats' responses to novelty in the T-maze: (1) a test of spontaneous alternation allowing separate measurement of place and body turn alternation; and (2) a test of entry into an arm of changed brightness (“response to stimulus change”). Chlordiazepoxide reduced spontaneous alternation by specifically weakening body turn alternation and eliminated the response to stimulus change. These findings are similar to those previously reported for the barbiturate sodium amylobarbitone. The same pattern of change in the two tests was seen after a low dose of the GABAA agonist muscimol (0.00125 mg/kg); when the dose of muscimol was raised (0.01 and 0.25 mg/kg), place alternation was also reduced. Picrotoxin but not bicuculline (both GABAA blockers) reversed the effects of muscimol and partially those of chlordiazepoxide on the response to stimulus change; in the spontaneous alternation test picrotoxin only marginally affected the response to 0.25 mg/kg muscimol and actually enhanced the effect of 0.000125 mg/kg. The GABAB agonist baclofen (1 mg/kg) acted in the test of response to stimulus change like chlordiazepoxide and muscimol; however, when baclofen was combined with muscimol, the two drugs tended to show mutual blocking. These results are generally consistent with the hypothesis that GABAergic mechanisms play a role in anxiolytic behavioural activity, but many details are difficult to explain.
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  • 115
    ISSN: 1432-2072
    Keywords: Delayed alternation ; Spatial memory ; Cortex ; Dopamine ; Noradrenaline ; 5-Hydroxytryptamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventeen male Sprague-Dawley rats were trained to eight to nine correct responses on a delayed spatial alternation test performed on alternate days in a T-maze. Locomotor activity in an observation box was scored on 2 consecutive days. The animals were killed 2 weeks after the end of behavioural testing and dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5HT), the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5HT metabolite, 5-hydroxyindoleacetic acid (5HIAA) determined in cortex, hippocampus, striatum and hypothalamus. Cortical concentrations of both DA and NA correlated negatively and significantly with the number of errors made in learning the alternation task, though the latter correlation was less striking and became negligible after the correlation between DA and NA was partialled out. Concentrations of DA and NA in the other regions did not correlate significantly with errors. None of the other neurochemical variables correlated significantly with either errors or locomotor activity, except for hypothalamic HVA concentration which showed a marginally significant correlation with locomotor activity. The above results, together with effects of brain lesions reported by other authors, strongly indicate that cortical catecholamines facilitate learning in the normal non-drug-treated rat.
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  • 116
    ISSN: 1432-2072
    Keywords: Dopamine ; D-1 and D-2 receptors ; SCH 23390 ; RU24213 ; Stereotypy ; 5-Hydroxytryptamine ; Ro22-2586 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the putative selective dopamine D-1 antagonist benzazepine SCH 23390 and of the selective dopamine D-2 antagonist Ro22-2586 on stereotypy induced by the selective D-2 agonist RU24213 were compared. RU24213 (0.5–15 mg/kg) dose-dependently induced stereotyped behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40–200 μg/kg Ro22-2586, but surprisingly blocked by 40–200 μg/kg SCH 23390. The selectivities of these compounds for dopamine receptor subtypes were verified in terms of their relative abilities to displace the in vitro binding of 3H-piflutixol to striatal D-1 receptors and of 3H-spiperone to D-2 receptors. As SCH 23390 fails to influence D-2 mediated prolactin secretion or emesis in vivo, there appears to be no significant formation of an active metabolite of SCH 23390 with D-2 antagonist activity. Because SCH 23390 has some affinity for 5-hydroxytryptamine receptors, any effect on the serotonergic behavioural syndrome induced by 10 mg/kg 5-methoxy-N,N-dimethyltryptamine was also studied. The serotonergic responses of hind limb abduction, reciprocal forepaw treading and Straub tail were unaltered after 40–200 μg/kg SCH 23390, indicating no significant 5-HT blockade or non-specific depressant action at these doses which might influence the expression of stereotypy. Thus, these data are consistent with blockade of tonic D-1 dopaminergic activity that may influence the expression of behaviours initiated byD-2 dopaminergic stimulation.
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  • 117
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    Psychopharmacology 87 (1985), S. 328-333 
    ISSN: 1432-2072
    Keywords: Khat ; Cathinone ; Amphetamine ; Conditioned taste aversion ; Adipsia ; Toxicity ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The potency of dl-cathinone (the active constituent of the Khat plant) was compared with that of d-amphetamine in the conditioned taste aversion (C. T. A.) procedure and in a test of drug-induced adipsia in rats. Both drugs induced C.T.A., the potency ratio being 1∶17 (amphetamine was more potent). Both drugs induced adipsia in deprived rats given access to water for 120 min. The potency ratio in this procedure was 1∶4. Potency in the C.T.A. procedure did not therefore correlate with potency in inducing adipsia; consequently drug-induced C.T.A. cannot be attributed to conditioned adipsia. In the adipsia test the drugs had similar durations of action, thus factors related to duration of drug action (cf Cappell and Le Blanc 1977) cannot account for the surprisingly low potency of cathinone in the C.T.A. procedure. These data, obtained with stimulant drugs with similar structures and similar actions in a variety of conventional in vivo and in vitro pharmacological tests, illustrate the unpredictable nature of drug actions in the C.T.A. procedure. The low potency of cathinone in inducing C.T.A. could not be predicted from knowledge of the potency of this compound in tests of adipsia (as shown here) or (as reported elsewhere) in tests of anorexia, locomotor stimulation, stereotypy, suppression of operant responding, drug discrimination, release and inhibition of reuptake of dopamine and noradrenaline, lethality and actions on the cardiovascular system. All of these studies have reported potency ratios considerably lower than 1∶17, which were nevertheless similar to the 1∶4 ratio observed in the adipsia test. It is suggested that the weak potency of cathinone in the C.T.A. procedure may be related to its comparatively potent reinforcing actions in the self-administration procedure.
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  • 118
    ISSN: 1432-2072
    Keywords: EEG ; Pentylenetetrazol ; Antiepileptic drugs ; Cluster analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristics of the PTZ-induced EEG paroxysms. Most compounds had moderate to potent anti-PTZ effects, as shown by the changes in the EEG temporal parameters. However, these effects depended on the drugs and doses. Cluster analysis showed that drugs and doses which evoked similar changes were closely related and were included in separate clusters with respect to one another. In particular, the present results showed that benzodiazepines and antiepileptics cluster differently in their effects. Thus, this model could be a useful tool for assessing new antiepileptic drugs.
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  • 119
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    Psychopharmacology 87 (1985), S. 351-356 
    ISSN: 1432-2072
    Keywords: Apomorphine ; Haloperidol ; Thioridazine ; Central drug administration ; Dopamine ; Feeding behaviour ; Microstructural analysis ; Eating rate ; Eating time ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anorectic effects of apomorphine were studied in a microstructural analysis paradigm. Low doses of apomorphine (〈0.1 mg/kg SC) reduced food intake, by reducting both the rate of eating and eating time. The neuroleptics haloperidol and thioridazine blocked the effect of apomorphine on eating time, but not on eating rate. Anorectic effects elicited by apomorphine administration to the ventral tegmental area and, to a lesser extent, the substantia nigra were mediated by a selective reduction of eating time. Effects of apomorphine on eating time appear to result from an action at presynaptic dopamine receptors; the mechanism of the effect of apomorphine on eating rate is unclear.
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  • 120
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    Psychopharmacology 87 (1985), S. 357-363 
    ISSN: 1432-2072
    Keywords: Delayed matching ; Short-term memory ; Cholinergic systems ; Nucleus basalis ; Fimbria-fornix ; Scopolamine ; Physostigmine ; Methamphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To provide a more specific test of memory impairments following lesions to central cholinergic systems, rats were trained on an operant delayed matching task. Ibotenic acid lesions of the nucleus basalis produced a disruption of performance at all delay intervals (a parallel downward shift in the delay-performance curve). By contrast, fimbriafornix transections had no effects at short delays, but produced a progressively greater impairment as the delays lengthened (an increased downward slope of the delay-performance curve). Scopolamine produced a dose-dependent disruption of performance, apparent at the shortest delays but greater at longer delays, that was similar to the two lesion deficits combined, whereas physostigmine induced a mild but significant enhancement of performance. The results support the hypothesis that disruption of hippocampal circuitries, including cholinergic afferents via the fimbria-fornix, produces short-term or working memory impairments, whereas disruption of the cortical cholinergic system implicates more stable long-term aspects of task performance. Peripherally administered cholinergic drugs produce both types of effect and thus may influence both systems.
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  • 121
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    Psychopharmacology 87 (1985), S. 368-370 
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Drug discrimination ; Rat ; SKF 38393 ; SKF 82526
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats (N=11) were trained to discriminate SKF 38393 (8.0 mg/kg, IP), a D1 dopamine receptor agonist, from saline in a two-lever, food-reinforced (FR 30) drug discrimination paradigm. The discrimination was acquired by nine rats within an average of 77±6 (SEM) sessions. Subsequently, various doses of SKF 38393 as well as SKF 82526, a potent, selective D1 agonist that does not readily penetrate the blood-brain barrier, were injected prior to test sessions. SKF 38393 (2–16 mg/kg) produced a dose-related increase in the percent of responses that occurred on the drug lever during test sessions. On the other hand, SKF 82526 (0.125 and 1.0 mg/kg) induced no drugappropriate responding. This experiment establishes that SKF 38393 can serve as a discriminative stimulus in rats. Furthermore, the observation that SKF 82526 did not substitute for SKF 38393 in this paradigm makes it unlikely that this effect involves a peripheral site of action. The results suggest the existence of a functional, behaviorally relevant D1 dopamine receptor in the CNS of rats.
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  • 122
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    Psychopharmacology 87 (1985), S. 425-429 
    ISSN: 1432-2072
    Keywords: Morphine ; Clonidine ; l-Nantradol ; Tolerance ; Shock avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interruption of a photobeam by rats was maintained under a continuous shock avoidance schedule, and moderate response rates were maintained at low shock frequencies. Responding decreased, and shock frequency increased, in a dose-dependent manner after acute injections of the narcotic morphine, the antihypertensive l-nantradol clonidine, and the cannabinoid l-nantradol. Clonidine and l-nantradol were about 100 times more potent than morphine for decreasing overall responding, and l-nantradol was about 3 times more potent than clonidine for decreasing escape responding. When drugs were given repeatedly prior to daily experimental sessions, tolerance developed to response rate decreases of morphine and l-nantradol within seven to ten sessions, but tolerance did not develop to rate decreases of clonidine for up to 30 sessions. Continued decreased responding by clonidine was antagonized by yohimbine, but not by prazosin or naltrexone. These results extend observations for the acute effects of l-nantradol and clonidine to operant responding under a schedule of continuous shock avoidance. Different potencies for drugs in the present and previous experiments suggest important effects of response topography on dose effects.
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  • 123
    ISSN: 1432-2072
    Keywords: Arginine vasopressin ; EEG ; Spectral analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several studies have suggested that arginine vasopressin (AVP) may act centrally as a neurohormone or neuromodulator to produce electrophysiological and behavioral effects. However, there are few reports of EEG effects of AVP in unanesthetized, behaving animals. In the present study the EEG effects of “behaviorally relevant” subcutaneous (SC) doses of AVP (6 μg/kg) known to raise blood pressure were compared to “behaviorally relevant” intracerebroventricular (ICV) doses (0.1–1.0 ng) and multiple “toxic” ICV doses (1.0 μg) of AVP. Central injections of toxic doses of AVP produced behavioral arrest, bodily barrel rolling, and EEG slowing, but did not induce electrographic signs of seizure activity. Comparison of the spectral characteristics of the EEG revealed some similarities in the distribution of power between SC and the 1.0 ng ICV dose; whereas ICV doses of 0.1 and 0.5 ng produced power distributions that were different from those seen following saline or SC doses of AVP. The similarities in EEG activity between SC injections and the 1.0 ng ICV dose suggest a common brain state may be induced by the two routes of administration in those dose ranges.
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  • 124
    ISSN: 1432-2072
    Keywords: Habenula ; Behavioural despair ; Nomifensine ; Swimming behaviour ; Stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Lister rats with bilateral lesions of the habenula nuclei were observed during two consecutive phases of a swim test. During the first phase of the test, when escape was not possible, lesioned animals demonstrated fewer changes of behaviour. Lesioned animals failed to utilise an introduced external cue and escape route in the second part of the test. Control rats treated with the antidepressant nomifensine showed few changes of behaviour during the inescapable phase of the test but an enhanced ability to escape. Nomifensine produced no improvement of escape behaviour in lesioned animals, suggesting that this behavioural effect of nomifensine in controls is dependent on the habenula relay. The data also suggest that more than one response in swim tests can serve as an index of depression.
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  • 125
    ISSN: 1432-2072
    Keywords: Morphine analgesic tolerance ; Environment distinctiveness ; Habituation ; Compensatory conditioning ; Overshadowing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The experiments reported here investigated the mechanisms of drug tolerance acquisition in environments differing in distinctiveness. Specifically, they examined the hypothesis that tolerance acquired in non-distinctive environments might involve habituation while tolerance acquired in distinctive environments involves a classical conditioning or associative learning mechanism. In Experiment 1, rats pre-exposed to injection-ritual cues (placebo injections) prior to acquisition of tolerance to morphine analgesia in distinctive or non-distinctive environments showed a typically attenuated tolerance response on an environment-change test. The magnitude of the attentuation was not affected by the distinctiveness of the acquisition environment. In Experiment 2, rats acquiring tolerance in distinctive or non-distinctive environments, but without prior injection-ritual pre-exposure, did not demonstrate an attenuation of tolerance on an environment-change test. Tolerance acquired in either environment was unaffected by a subsequent rest period in the colony room, but was attenuated by a subsequent period of daily placebo injections in the colony room. It is argued that failure to observe environment-specific tolerance, as in Experiment 2 and in previous reports in the literature, may reflect overshadowing of environmental stimuli by injection-ritual stimuli, and are not indicative of a fundamental difference between the mechanisms of tolerance acquisition in environments varying in distinctiveness.
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  • 126
    ISSN: 1432-2072
    Keywords: Exploration ; Locomotor activity ; Sedation ; Chlordiazepoxide ; Benzodiazepine ; CL 218,872 ; Benzodiazepine antagonists ; Ro 15-1788 ; CGS 8216 ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of CL 218,872, initially classified as a non-sedative anxiolytic, were investigated and compared with those of chlordiazepoxide in the holeboard. The ability of two drugs that antagonise the effects of benzodiazepines, CGS 8216 and Ro 15-1788, to reverse the effects of CL 218,872 and chlordiazepoxide were also investigated, to see whether their effects might be mediated via benzodiazepine receptors. CL 218,872 (10 mg/kg) was found to be significantly sedative in both mice and rats (i.e., both locomotor activity and head-dipping were significantly decreased). In mice, the effects of CL 218,872 and of chlordiazepoxide were very similar over a range of doses, except that the stimulatory effect seen with low doses of chlordiazepoxide on head-dipping just failed to reach significance with CL 218,872. This study is in agreement with recently published results from different tests showing that sedative effects can be obtained with doses of CL 218,872 that are low and not much higher than those leading to anxiolysis. The sedative effects of both CL 218,872 (10 mg/kg) and chlordiazepoxide (20 mg/kg) were significantly reversed by RO 15-1788 (10 and 20 mg/kg) and CGS 8216 (10 mg/kg), suggesting that their effects are mediated via benzodiazepine receptors. The increase in head-dipping seen with chlordiazepoxide (2.5 mg/kg) was also reversed by RO 15-1788 and CGS 8216.
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  • 127
    ISSN: 1432-2072
    Keywords: DA D-1 receptors ; DA D-2 receptors ; Circling behaviour ; Dopamine agonists ; Dopamine antagonists ; 6-OHDA lesions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3H-DA in rabbit striatal slices (D-2) and the affinity to 3H-piflutixol (D-1) and 3H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis(Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis(Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis(Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists. Furthermore, the results indicate that both DA D-1 and D-2 receptors are involved in the effect of apomorphine, since selective antagonists induced maximally 50% inhibition. Complete blockade was only found in combination experiments and by the mixed D-1/D-2 antagonists cis(Z)-flupentixol, cis(Z)-clopenthixol, and clozapine.
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  • 128
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    Psychopharmacology 86 (1985), S. 81-83 
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Haloperidol ; Conditioned taste aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using in rats a Conditioned Taste Aversion (CTA) procedure, chlorpromazine was shown to possess significant US properties at the highest dose tested (8 mg/kg IP repeated four times). In contrast, haloperidol failed to exert a similar effect at a dosage (1.6 mg/kg IPx4) at least twice as high, in terms of pharmacological activity, as the effective chlorpromazine dosage. These data suggest that the induction of neuroleptic extrapyramidal side effects and the antidopaminergic properties shared by the two drugs may not be responsible for the aversive effect of chlorpromazine. However, it cannot be excluded than haloperidol produces an aversion which is antagonized by some action of the drug not shared by chlorpromazine.
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  • 129
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Lithium chloride ; Conditioned Taste Aversion ; Extinction ; Housing condition ; Isolation ; Social behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were used in two experiments to investigate the influence of social variables on the acquisition of Conditioned Taste Aversion (CTA) to either lithium chloride (10 ml/kg IP of a 0.3-M solution given twice) or chlorpromazine (8 mg/kg IP given four times) and on subsequent extinction. CTA acquisition was not affected by original housing assignment (isolation or paired housing for 15–23 days prior to conditioning), by the shifted social assignment during conditioning, or by the drugged state of the paired animals' partners on drug-scheduled days. However, for both drugs, permanently isolated animals extinguished CTA more slowly than rats housed permanently in pairs. Shifts from isolation to pairing or vice versa failed to alter CTA extinction in the case of lithium, but affected it significantly in chlorpromazine-treated rats. Shifts from isolation to paired housing with an undrugged partner produced faster extinction for lithium than the corresponding group with a drugged partner. For chlorpromazine, the effect of the same shift was exactly the opposite. Overall, the results show that changes in CTA extinction can be a function of social variables.
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  • 130
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    Psychopharmacology 85 (1985), S. 469-475 
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Lisuride ; Ergot derivatives ; Acoustic startle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five ergot-related compounds were examined for their effects on the acoustic startle response in the rat. The startle amplitude and the startle latency were registered. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.5–8 mg/kg) and lisuride (0.05–0.8 mg/kg) were found to enhance the startle amplitude, while the mainly DA receptor active ergot derivatives pergolide (0.2–0.8 mg/kg), bromocriptine (5–20 mg/kg) and LY 141865 (5–20 mg/kg) had no, or even the reverse, effect. All five compounds caused a prolongation of the startle latency. The increased startle amplitude caused by 8-OH-DPAT (2 mg/kg) and lisuride (0.2 mg/kg) was successfully antagonized by the 5-HT receptor antagonist methiothepin (0.1 mg/kg) but not by metergoline (1 mg/kg). 5-Hydroxy-L-tryptophan (L-5-HTP; 12.5–50 mg/kg), administered to pargyline- and benserazide-pretreated animals, was included for comparison. The serotonin precursor caused a marked increase in the startle amplitude and a shortening of the startle latency.
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  • 131
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; Noradrenaline ; Dopamine ; Serotonin ; Monoaminergic agonists ; Open field locomotor activity ; Forced swim test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraaccumbens injections of catecholamines noradrenaline and dopamine, though not of serotonin, stimulated locomotion by rats in an open field, 10–15 min later. Similar effects were observed 5 min after microinjection of apomorphine whereas clonidine only attenuated locomotor activity. On the other hand, intraaccumbens administration of phenylephrine, isoproterenol and quipazine, in doses similar to an effective dose of noradrenaline, did not alter rat open field behavior. The escape-directed activity of rats in the forced swim test (FST) was stimulated 5 min after local administration of noradrenaline, phenylephrine, isoproterenol or apomorphine only. No effects in the FST were observed 15 min after noradrenaline injection or after intracaudate noradrenaline administration. The stimulatory effects of intraaccumbens noradrenaline injection in the FST were antagonized by the local pretreatment of rats with phentolamine, though not with propranolol. Accordingly, it is possible to conclude that both catecholamines, but not serotonin, play complex and probably distinct roles within the nucleus accumbens in the stimulation of activity by rats in the FST and the open field test.
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  • 132
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    European journal of pediatrics 143 (1985), S. 203-208 
    ISSN: 1432-1076
    Keywords: Farber disease ; Lipogranulomatosis ; Acid ceramidase deficiency ; Arthropathy ; Hoarseness ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 20-month-old girl showed typical clinical signs of Farber disease: hoarseness since birth, and periarticular subcutaneous painful nodules. Complete deficiency of acid ceramidase activity was found in cultured skin fibroblasts. An electron microscopic examination of a dermal nodule disclosed pathognomonic tubular inclusions in histiocytes. In epidermal cells zebra-body-like and needle-like lysosomal inclusions were found. Their ultrastructure is different from that of the intrahistiocytic lysosomal inclusions. Probably three clinical types of Farber disease may be distinguished according to the symptomatology and the course of the discase: a severe type, an intermediate type and a relatively mild type. The activity of acid ceramidase does not correlate with prognosis of the disease, while a correlation between first appearance of dermal nodules and clinical course appears likely.
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  • 133
    ISSN: 1432-0738
    Keywords: 2,4,6-Trinitrotoluene ; Carcinogens ; 2,4-Dinitrotoluene ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4,6-Trinitrotoluene (TNT) is structurally related to the rat liver carcinogen 2,4-dinitrotoluene (technical grade), and both compounds are known to be mutagenic to bacteria in vitro. TNT is therefore established as a potential rodent carcinogen; the present paper describes experiments designed to assess if this potential is likely to be expressed in appropriately exposed animals. TNT gave a negative response in the mouse bone marrow micronucleus assay and in an in vivo/in vitro rat liver assay for unscheduled DNA synthesis (UDS). In the latter assay animals are exposed to the test chemical in vivo and their hepatocytes subsequently evaluated for UDS in vitro. The negative response observed for TNT in the liver assay at dose-levels up to 1000 mg/kg was accompanied by a positive response for the hepatocarcinogen 2,4-dinitrotoluene at the lower dose-level of 200 mg/kg. In contrast, the dinitro compound gave a negative response in the micronucleus assay, as was also observed for TNT. It is concluded that the negative response observed for TNT in the liver assay indicates that it is unlikely to be a rat hepatocarcinogen. Nonetheless, high levels of methaemoglobin were observed in the TNT-treated rats and their urine was coloured red. These facts, together with the known toxicities of this agent suggest a possible carcinogenic hazard to the haemopoetic and urinary tissues of animals exposed chronically to it at toxic dose-levels.
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  • 134
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    Archives of toxicology 57 (1985), S. 226-230 
    ISSN: 1432-0738
    Keywords: Di-(2-ethylhexyl) phthalate ; Mono-(2-ethylhexyl) phthalate ; Plasma level ; Disposition ; Oral dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dispositon of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) was studied in the rat. Three hours after a single oral dose of DEHP (2.8 g/kg), plasma concentrations of 8.8±1.7 μg/ml DEHP and 63.2±8.7 μg/ml MEHP were reached. MEHP levels declined with a half-life of 5.2±0.5 h. The ratio of the area under the plasma concentration-time curve of MEHP to that of DEHP was 16.1±6.1. When 14CDEHP was administered, 19.3±3.3% of the radioactivity was excreted in the urine within 72 h, the rest being excreted in the faeces. The urinary excretion rate of total radioactivity declined with a half-life of 7.9±0.5 h. Single administration of MEHP (0.4 g/kg) resulted in plasma concentrations of 84.1±14.9 μg/ml 3 h after dosing; the half-life of MEHP was 5.5±1.1 h. Multiple dosing with DEHP (2.8 g/kg/day) for 7 consecutive days produced no accumulation of DEHP or MEHP in plasma.
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  • 135
    ISSN: 1432-0738
    Keywords: Thiabendazole ; Adenosine triphosphate ; Teratogenesis ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ogata et al. (1984) reported that thiabendazole (TBZ) was teratogenic in mice when olive oil was used as a vehicle, but not teratogenic when administered in gum arabic. Results of investigations into the possible association between TBZ-induced teratogenicity and adenosine triphosphate (ATP) are reported here. ATP levels in the limb buds were measured at day 10 of gestation in controls and mice treated with 1300 mg/kg TBZ 24 h previously. The results showed that there was a correlation between the dosage of TBZ and the ATP levels of fore and hind limb buds (r=−0.827 and r=−0.799, respectively). ATP levels in mouse limbs were reduced to 22–31% of control values when TBZ was given in olive oil, but the ATP reduction was only 6–9% when TBZ was given in gum arabic. This suggests that there may be a relationship between the teratogenic and ATP-depressing action of TBZ on the limb buds of mouse embryos. Pregnant rats were also treated with TBZ. TBZ at a dose level of 1000 mg/kg was given orally on day 11 of gestation. After 24 h, ATP levels in fetal rat limbs were still 82% of control values. These results confirm the observations of Ogata et al. on the vehicle effect and the difference in response between mice and rats.
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  • 136
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    Archives of toxicology 56 (1985), S. 252-255 
    ISSN: 1432-0738
    Keywords: Cadmium ; Selenium ; Liver ; Kidney ; Rat ; Metallothionein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In acute studies, approximately 70–90% of cytosolic cadmium in liver and kidney has been shown to be bound to metallothionein, a low-molecular weight protein. In this study, we report on the influence of dietary selenium on the distribution of cadmium in rat kidney and liver. Contrary to the findings of most acute studies, our results indicate that only a relatively small proportion of cadmium (approximately 14% in the kidney and 44% in the liver) is bound to metallothionein when cadmium is administered for 7 weeks in the diet and via osmotic minipumps to selenium-deficient rats. Feeding rats the same diet supplemented with 1.0 ppm selenium results in no detectable cadmium-metallothionein peak in the kidney, and only about 10% of the cytosolic cadmium elutes as cadmium bound to metallothionein in the liver. In animals fed the selenium-supplemented diet, the bulk of the cadmium is recovered in the low-molecular weight fraction. Dietary selenium did not significantly affect the distribution of zinc and copper in the kidney or liver.
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  • 137
    ISSN: 1432-0738
    Keywords: 1-Deamino-2-tyr(ethyl) oxytocin (dEtOT) ; Peri-and postnatal effect ; Growth retardation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 1-deamino-2-tyr(ethyl) oxytocin (dEtOT) upon peri- and postnatal development of the rat was studied in two experiments when administered between day 15 of pregnancy and the day of parturition. The investigation showed that dEtOT did not affect the pups at birth, that dEtOT caused a dose-related growth retardation of the pups, that the growth inhibiting effect was directly correlated to the length of administration and that the growth inhibiting effect was more pronounced if dEtOT was given close to parturition than if it was given earlier in the pregnancy. In addition, the growth retardation was not due to an effect on the pups but to an effect on their mothers, probably related to inhibition of the emptying mechanisms of the mammary glands, meaning that the pups were insufficiently fed by their mothers immediately after birth.
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  • 138
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    Archives of toxicology 56 (1985), S. 167-169 
    ISSN: 1432-0738
    Keywords: Heavy metal salts ; Mixed function oxidases ; Cytochrome P-450 ; ALA synthetase ; Heme oxygenase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of Co(NO3)2, CdSO4, NiSO4, ZnSO4, and HgCl2 (given repeatedly in subtoxic doses in the drinking water for 30 days) on rat liver monooxygenases was studied in experiments on male Wistar rats. The salts of Co, Cd, and Zn increased the activity of benzphetamine-N-demethylase, the content of cytochrome P-450 and microsomal heme. The data suggest that these salts exert an enzyme-inducing effect on the hepatic monooxygenases. The same metal salts (Co, Cd, and Zn) increased the activity of δ-aminolevulinic acid (ALA) synthetase and decreased that of heme oxygenase. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein. HgCl2 and NiSO4 did not exert an enzyme-inducing action. The lack of change in the activity of NADPH-cytochrome c reductase and cytochrome b5 (except for ZnSO4) suggests that these components of the electron transport chain are not likely to be involved in the enzyme-inducing action of the heavy metal salts.
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  • 139
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    Archives of toxicology 56 (1985), S. 204-206 
    ISSN: 1432-0738
    Keywords: Peripheral neuropathy ; 2,5-hexanedione ; Conduction velocity ; Distal latency ; Vitamin B12 ; Vitamin B6 ; Therapeutic effects ; Rat ; Tail nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The therapeutic effect of Vitamin B12 or Vitamin B6 on 2,5-hexanedione induced-neuropathy in animals was examined by using our electrodiagnostic technique in order to investigate the mechanism of the development of the neuropathy. Pyridoxal phosphate and two forms of Vitamin B12 were administered to rats intoxicated by the neurotoxin for a period of 18 weeks, and the sensory and motor fiber conduction velocity and the motor distal latency of the tail nerve were periodically determined. None of the groups treated with the therapeutic drugs exhibited a definite improvement in the nerve fiber conduction velocity and motor distal latency of the rat tail nerve, as compared with those of the 2,5-hexane-dione-treated controls.
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  • 140
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    Archives of toxicology 56 (1985), S. 212-213 
    ISSN: 1432-0738
    Keywords: Piroxicam ; Indomethacin ; Gastric ulcers ; Ulcer Index ; Therapeutic doses ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Comparative toxicity of indomethacin and piroxicam at low multiples of the human therapeutic dose was studied in inbred albino rats of both sexes. Using the drug-induced model, the two drugs were used to produce gastric ulcers in the rat. Both showed significant evidence of gastric ulceration measured by the ulcer index. The incidence of ulceration increased with dose for both drugs. Piroxicam produced a lower incidence of gastric ulcers than equivalent doses of indomethacin.
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  • 141
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    Archives of toxicology 56 (1985), S. 236-241 
    ISSN: 1432-0738
    Keywords: Methylmercury ; RNA synthesis ; Dorsal root ganglion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of methylmercury in vivo on the incorporation of 3H-uridine in vitro into RNA of dorsal root ganglia of the rat was examined. Modified methods for the incubation of the tissue and extraction of RNA were applied to adequately determine the rate of RNA synthesis. Methylmercury significantly decreased the RNA content and RNA synthetic activity only in the symptomatic period, while uptake of the precursor into the acid-soluble pool remained unchanged. These results indicate that the previously reported inhibition of protein synthesis in dorsal root ganglia at an early phase of methylmercury intoxication was not due to impairment RNA synthesis in this tissue.
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  • 142
    ISSN: 1432-0738
    Keywords: Oral cadmium ; Placenta ; Foetal organs ; Zn, Cu, Fe content ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cadmium chloride was administered in drinking water at a concentration of 50 ppm cadmium to female rats for 20 days of gestation. The foetuses were then removed from the uteri of the dams. Gestational exposure to oral cadmium resulted in decreased zinc, copper, iron, metallothionein, and thionein-bound zinc content in foetal liver as well as in reduced copper content in placenta and foetal intestine, brain and kidney. Subcellular fractionation of the foetal liver revealed decreased nuclear and cytoplasmic zinc content as well as decreased microsomal iron content. Pregnant rats exposed to oral cadmium revealed decreased serum zinc and iron concentration as well as reduced ceruloplasmin activity. The decreased zinc, copper, and iron content in foetal organs is suggested to be causally connected with the diminished availability of these metals in the maternal circulation.
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  • 143
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    Archives of toxicology 56 (1985), S. 279-282 
    ISSN: 1432-0738
    Keywords: Hypothalamus ; Hypothermia ; Rat ; Thermogenesis ; Tributyl phosphorotrithioate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tributyl S,S,S-phosphorotrithioate (DEF) produces profound hypothermia in rats, mice and guinea pigs by inhibition of thermogenesis. Its actions on heat conservation and motor control are, however, minimal. It is effective against both shivering and non-shivering thermogenesis and completely blocks the increase in body temperature evoked by anterior hypothalamic stimulation. A number of other measures indicated that this is unlikely to be due to a lack of peripheral thermogenic capacity: thus plasma concentrations of glucose, free fatty acids, and ketone bodies remained normal or rose after DEF, and in vitro noradrenaline-stimulated lipolysis was normal in the presence of DEF. The metabolic response to the uncoupler, 2,4-dinitrophenol was unchanged by DEF, and the increase in temperature of brown fat evoked in vivo by nerve stimulation or noradrenaline was also unaffected. It is suggested that DEF (or more likely a DEF metabolite) acts selectively on a central thermogenic control process.
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  • 144
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    Archives of toxicology 57 (1985), S. 72-73 
    ISSN: 1432-0738
    Keywords: Parathion ; Gastrointestinal transit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possibility of in vivo or post-mortem acceleration of gastrointestinal transit was investigated in the rat after sublethal or lethal doses of the insecticide parathion. Parathion did not change gastrointestinal transit time before or after death in the poisoned rat.
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  • 145
    ISSN: 1432-0738
    Keywords: Mercury ; Metallothionein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of the administered mass on the tissue and sub-cellular distribution of mercury (Hg) was investigated in rats, using 203Hg. The fraction of the dose deposited in liver increased threefold over the dose range 0.17–1.65 mg Hg · kg−1, while the retention in the kidney decreased by a factor of 2. The uptake in other organs, lung, spleen, brain, thymus, salivary glands showed no dose-dependent variation. Subcellular fractionation studies showed a dose-dependent increase in the Hg content of the liver cytosol, with corresponding decreases in the deposition in the lysosomal and nuclei-cell debris fractions. In contrast, no clear changes in the distribution of Hg amongst the subcellular organelles of the kidney were observed. The amount of Hg bound to metallothionein in the liver cytosol rose steeply with increasing dose. However, in the kidney cytosol the mass of Hg bound to metallothionein increased with dose up to 0.55 mg Hg · kg−1, thereafter remaining approximately constant. These observations suggest that the Hg-binding metallothionein in the kidney was saturated by administered doses greater than 0.55 mg Hg · kg−1, whereas in liver saturation levels of the metal were not reached even at the highest dose tested, 1.65 mg Hg · kg−1.
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  • 146
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    Archives of toxicology 57 (1985), S. 53-55 
    ISSN: 1432-0738
    Keywords: Behavior ; Brain ; Catecholamines ; Serotonin ; Styrene ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male albino rats were administered styrene in groundnut oil, PO at doses of 100 mg and 200 mg/kg body weight daily for 14 consecutive days. No neurological deficit was observed in any animal during the course of the experiment. Mean % avoidance response (learning) for each treated group, from day 1 to day 4 of conditioned avoidance response training, revealed a general increase. Styrene significantly increased the % avoidance response at both doses as compared to controls, although no definite dose-response relationship was evident. No significant difference was noted in the spontaneous locomotor activity and regional brain catecholamine levels, between controls and treated rats of either dose. Serotonin levels in hippocampus, hypothalamus, and mid-brain were significantly raised at the higher dose of styrene. Therefore, elevated serotonin levels in these brain regions may account for styrene-induced learning.
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  • 147
    ISSN: 1432-0738
    Keywords: Chromium (VI) ; Inhalation ; Rat ; Alveolar macrophages ; Immune response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In inhalation chambers, 5-week-old male Wistar rats of the strain TNO-W-74 were continuously exposed to submicron aerosols of sodium dichromate in concentrations from 25 (low level) to 200 μg/m3 Cr (high level). Subacute exposure (28 days) to 25 and 50 μg/m3 Cr resulted in “activated” alveolar macrophages with stimulated phagocytic activities, and significantly elevated antibody responses to injected SRBC's. After subchronic (90 days) low level exposure there was a more pronounced effect on activation of the alveolar macrophages, with increased phagocytic activities. However, at high Cr (VI) exposure level (200 μg/m3), inhibited phagocytic function of the alveolar macrophages was seen. In rats which were exposed to this chromium aerosol concentration for 42 days, the lung clearance of inert iron oxide was reduced significantly. The humoral immune system was still stimulated at subchronic low chromium aerosol concentrations of 100 μg/m3, but significantly depressed at 200 μg/m3 Cr. These results show that respiratory defence and immunologic functions were stimulated or inhibited depending on dose and time of chromium (VI) inhalation.
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  • 148
    ISSN: 1432-1459
    Keywords: Tangier disease ; Polyneuropathy ; Ultrastructure ; Biopsy findings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Polyneuropathy in Tangier disease can be divided into three clinical types. The most severe form (type III) with a syringomyelia-like syndrome has been described in three cases only. Here, a fourth case of this type is presented. Because of unusual trophic disturbances even leprosy was suspected. Electrodiagnostic findings, including evoked cerebral potentials in this case, were suggestive of a generalized neuropathy with some degree of primary or secondary demyelination and implied possible impairment of central structures. Sural nerve biopsy, including electron microscopy and quantitative analysis, revealed a predominant reduction of smaller myelinated and unmyelinated fibres. The main morphological feature was the abundance of abnormal non-membrane-bound vacuoles in Schwann cells, mostly of the unmyelinated type, and in some endoneurial fibroblasts, macrophages and perineurial cells. There was no inverse relationship between lipid vacuoles and axons in Schwann cell complexes as supected by others. An excess of endoneurial collagen as well as an increased fascicular area were obvious. In five skin biopsy specimens of different regions typical vacuoles were noted in Schwann cells, histiocytes, nevus cells, and rarely in perineurial cells.
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  • 149
    ISSN: 1432-072X
    Keywords: Cyanophyta ; Chroococcidiposis ; Lichenphycobiont ; Cell wall ; “Outer membrane” ; Ultrastructure ; Freeze fracturing/etching ; Patchwork-like leaflet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Freeze etching studies in a symbiotic and a freeliving strain of Chroococcidiopsis revealed a specific layer in the outer cell wall not described so far from Cyanophyta. The layer showed a complex organisation: The main unit are ribbons, 2–3 nm thick, striated at right angle to the longitudinal axis. They are interwoven to a patchwork-like leaflet. The ribbons are virtually composed of globular particles associated in parallel rows. The cytoplasmic membrane and the cell walls of the symbiotic and the free-living strain were compared.
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  • 150
    ISSN: 1432-2072
    Keywords: Duration of punishment ; Delay of reward ; Behavioral suppression ; Benzodiazepines ; Diazepam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigated in rats whether variables which may affect the animals' tolerance for delay of reward could be critical for the benzodiazepine-induced release of punished behavior. Rats were subjected to conflict situations during which signalled FR4 non-punished periods (lights-off) alternated with punished periods of different durations signalled by lights-on stimuli. Lever presses during punished periods resulted in the delivery of both one food-pellet and one electric foot-shock (0.45 mA). The antipunishment effect of diazepam (2 mg/kg IP) clearly depended on the duration of the punished periods, release of punished behavior being observed only when punished periods exceeded 1 min. The duration of punished periods required for diazepam-induced release of responding was affected by factors which modified the contrast between rewards received in punished and non-punished periods. One of these factors was the FR schedule imposed during non-punished periods, since the anti-punishment effect of diazepam was observed during short-lasting (30-s and 1-min) punished periods separated by FR24 non-punished periods. A second factor was the ratio of the durations of punished and non-punished periods: diazepam released behavior during 2-min punisheds when the duration of the intercurrent non-punished periods was 1 min, but not when it was 4 min. The predictability of the duration of the punished periods also modulated the effect of diazepam since: with 1 min punished periods, diazepam released punished responding during the first exposures of the rats to the experimental session, but lost part or all its efficacy in animals extensively trained to the procedure. It is tentatively proposed that not only punishment, but also delay of reward induced by passive avoidance of the punished response, are affected by benzodiazepines.
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  • 151
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    Psychopharmacology 85 (1985), S. 340-345 
    ISSN: 1432-2072
    Keywords: 5-HT ; 5-MeODMT ; Anti-aversive effect ; Antagonism by metergoline and ketanserin ; Potentiation by zimelidine ; Dorsal periaqueductal grey ; 5-HT2 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Microinjection of 5, 10, and 20 nmol serotonin (5-HT) and of 0.5, 1, and 2 nmol 5-methoxy-N, N-dimethyltryptamine (5-MeODMT) into the dorsal midbrain of rats bearing chronically implanted chemitrodes raised the electrical threshold for inducing escape behaviour following stimulation of the dorsal periaqueductal grey matter (DPAG). Linear regressions of log dose against drug-induced increase in aversive threshold were obtained for 5-HT and 5-MeODMT. The 5-MeODMT dose-effect curve was steeper and lay to the left of the 5-HT dose-effect curve. Local pre-treatment with 10 nmol metergoline or ketanserin blocked the anti-aversive effect of 10 nmol 5-HT, whereas pre-treatment with 100 nmol zimelidine potentiated this effect of 5-HT. The same dose of zimelidine raised the aversive threshold when given alone. These results suggest that 5-HT plays an inhibitory role in the DPAG controlling aversion, probably mediated by 5-HT2 receptors.
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  • 152
    ISSN: 1432-2072
    Keywords: Tracking ; Visual discrimination ; Switching ; Perseveration ; Attention ; d-Amphetamine ; Chlordiazepoxide ; Alpha-flupenthixol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to respond to one of two levers under a random ratio schedule of food reinforcement. Which of the levers was correct was redetermined before each response and signalled by a light. The effects of d-amphetamine (0.2–3.2 mg/kg), chlordiazepoxide (1–8 mg/kg), and the neuroleptic alpha-flupenthixol (0.03–0.33 mg/kg) on the efficiency of rats tracking this visual cue were examined. d-Amphetamine increased the proportion of responses made on the correct lever at low and intermediate doses, but reduced the proportion at 3.2 mg/kg. At the highest dose, chlordiazepoxide produced a small increase in this measure, together with a reduction in response rate, but alpha-flupenthixol had no effect, even at a dose reducing response rate. Low doses of amphetamine also increased switching between the levers, producing a proportionately greater increase in switching from the correct lever to the incorrect lever than vice versa. The results are interpreted as showing that d-amphetamine facilitates tracking performance as a result of its action of enhancing response switching, and supporting the hypothesis that facilitation of performance by amphetamine-like drugs depends on the effect of the drug on response output coinciding with task requirements.
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  • 153
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    Psychopharmacology 86 (1985), S. 480-486 
    ISSN: 1432-2072
    Keywords: Propranolol ; Beta-adrenergic blocker ; Differential reinforcement of low rates of response (DRL) ; Anxiety ; Antianxiety drugs ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained over 40 days to lever-press for food reward under a schedule of differential reinforcement of low rates of response with a 20-s criterion (DRL 20), following seven sessions of continuous reinforcement. The effect of injecting a beta-adrenergic blocker, propranolol (5 mg/kg IP), before and at two different delays after each daily session of DRL were investigated. In Experiment I, rats drugged 5–8 min before every session earned fewer reinforcements compared to controls, and showed impaired temporal discrimination. In Experiment II, this result was not replicated, but similar effects were clear in animals drugged pre-session from the 15th day of acquisition. By contrast, an improved temporal discrimination, and increased number of reinforcements were seen in rats drugged 5–8 min after every session. In Experiment III, the postsession effects were replicated and found also in rats drugged 4–5.5 h after each session. These results suggest that propranolol has an acute effect on DRL responding which resembles that of anxiolytics, and a chronic effect which opposes the acute one.
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  • 154
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    Naunyn-Schmiedeberg's archives of pharmacology 330 (1985), S. 147-154 
    ISSN: 1432-1912
    Keywords: Gastric parietal cells ; cAMP ; cGMP ; Gastric acid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Just as cAMP is regarded as an intracellular mediator of histamine, so has cGMP been connected with cholinergic stimulation of gastric acid secretion. The object of the present investigation was to study the possible role of cellular cGMP on 14C-aminopyrine uptake, an indirect measure of parietal cell H+-production, by using mixtures of isolated rat gastric cells and fractions with different parietal cell content. Cellular cAMP and cGMP. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) enhanced the cAMP and cGMP of gastric cells in a time- and concentration-dependent manner, by 98 and 124% (1 mmol/l) and was included in all further studies. In parietal cell enriched fractions, histamine elevated cAMP by 109% (100 μmol/l) without changing cGMP while carbachol did not influence either nucleotide. Various thiols and nitrogen compounds strongly enhanced cellular cGMP, e. g. hydroxylamine and l-cysteine (1 mmol/l) by 527 and 656%, whereas changes in cAMP were minimal. The hydroxylamine response occurred in parietal cell depleted and enriched fractions. 14 C-aminopyrine (AP) uptake. IBMX alone reduced the basal AP uptake, potentiated the effect of histamine and inhibited the effect of carbachol, which alone stimulated basal accumulation by 302%. The most efficacious stimulant of parietal cell H+-production was dibutyryl cAMP (582%, 100 μmol/l), whereas dibutyryl cGMP was without effect. However, this latter compound (1 mmol/l) reduced AP accumulation due to dibutyryl cAMP almost completely. Thiols and nitrogen compounds all more or less reduced AP uptake. The data contraindicate the theory of a second messenger function for cGMP in cholinergic acid stimulation of the rat stomach. They show, that an increase in cGMP is associated with low H+-production, even if cAMP levels are raised above their resting state. Thus, the results suggest that cGMP rather mediates inhibition of acid secretion, possibly by counteracting the messenger function of cAMP.
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  • 155
    ISSN: 1432-1912
    Keywords: Desipramine ; p-Chlorophenylalanine ; Locomotion ; Rat ; Beta receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The decrease in the B max value of 3H-dihydroalprenolol (3H-DHA) binding to cortical membranes of rat brain induced by long-term administration of desipramine (DMI) was prevented by concomitant treatment with parachlorophenylalanine (pCPA). Acute administration of DMI significantly decreased locomotor activity in saline- and (pCPA)-pretreated rats. DMI-induced inhibition of locomotor activity was abolished in (pCPA)-pretreated rats chronically treated with DMI. Conversely, in pCPA-pretreated animals, acute DMI could still significantly decrease the locomotion of chronically DMI-treated rats. The data presented indicated that an intact serotoninergic system is required to enable antidepressant drugs to induce biochemical and behavioral changes following their chronic administration.
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  • 156
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    Naunyn-Schmiedeberg's archives of pharmacology 328 (1985), S. 253-257 
    ISSN: 1432-1912
    Keywords: Clonidine ; Insulin ; Glucose ; Hyper-responsiveness ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effect of chronic clonidine treatment on the response to glucose of rat pancreatic B-cells was investigated. Clonidine treatment was carried out for 10 days by dissolving the drug into drinking water at a concentration of 10 μg/ml. Control rats were given drug-free tap water. Serum insulin responses to glucose (750 mg/kg, i. v.) of clonidinetreated rats were much smaller than those of control rats. However, after 1 day's withdrawal of clonidine, the rise in the serum insulin level induced by glucose was approximately 2-fold larger in clonidine-treated rats as compared to that in control rats. Since clonidine treatment decreased body weight of the rat by 10%–20% in 10 days, the same experiments were carried out with rats whose body weight loss was made comparable to that of clonidine-treated rats by restricting food for 10 days. Then, some animals of the group thus treated had food-restriction discontinued for 1 day. In both of the above two groups, no increment in glucoseinduced rise in serum insulin level was observed. Islets of Langerhans isolated from clonidine-treated rats showed pronounced insulin releasing capacity in response to glucose. Insulin content per islet of the clonidine-treated rat was slightly larger than that of control rat. These results indicate that the enhancement of serum insulin response to glucose following clonidine treatment is mainly attributable to the hyper-responsiveness developed in the pancreatic B-cells.
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  • 157
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    Naunyn-Schmiedeberg's archives of pharmacology 330 (1985), S. 93-96 
    ISSN: 1432-1912
    Keywords: Anticociceptive action ; Mouse ; Nonopioid ; Rat ; Tizanidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antinociceptive action of tizanidine [5-chloro-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole], a centrally acting muscle relaxant, was evaluated after subcutaneous or peroral administration in mice and rats. Tizanidine strongly inhibited the writhing response induced by acetic acid, phenyl-p-benzoquinone and acetylcholine in mice, and its potency was found to be greater than that of morphine. Tizanidine showed antinociceptive action like morphine not only in tail pressure and electrical stimulation tests in mice but also in tail-flick tests in mice and rats. The antinociceptive action of tizanidine was unaffected by pretreatment with naloxone. These findings suggest that tizanidine develops relatively strong antinociceptive action by a nonopioid mechanism.
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  • 158
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    International orthopaedics 9 (1985), S. 41-47 
    ISSN: 1432-5195
    Keywords: De Quervain ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les gaines tendineuses du court extenseur et du long abducteur du pouce ont été étudiées du point de vue histologique et ultrastructural chez quatre patients atteints de maladie de de Quervain. Dans les gaines tendineuses, beaucoup plus épaisses que normalement, ont été identifiées trois couches différentes. La couche externe et la couche intermédiaire sont formées d'épais faisceaux de fibres collagènes qui contiennent peu de fibroblastes. La couche interne est formée principalement d'un tissu myxoïde et chondroïde; les fibrilles collagènes sont plus épaisses que la normale, atteignant le diamètre de 2100 nanomètres. De nombreuses cellules semblables à des «myofibroblastes» sont présentes dans toutes les couches de la gaine. Nos résultats semblent indiquer que l'augmentation d'épaisseur et de consistance de la gaine tendineuse du court extenseur et du long abducteur du pouce dans la maladie de de Quervain, est causée par l'augmentation de la synthèse de la matrice extra-cellulaire, par l'augmentation d'épaisseur des fibrilles collagènes et par des aires de métaplasie myxoïde et chondroïde.
    Notes: Summary The tendon sheaths of extensor pollicis brevis (EPB) and abductor pollicis longus (APL), obtained from four patients with de Quervain's disease were studied by light and electron microscopy. Three different layers were identified in the sheath which was much thicker than normal. Both the outer and the middle layers had thick bundles of collagen fibres with scattered fibroblasts. The inner layer was mainly formed by chondroid and myxomatous tissue. Collagen fibrils were thicker than normal, reaching 2100 nm in diameter. Numerous cells which resembled «myofibroblasts» were scattered throughout the whole thickness of the sheath. The results seem to indicate that thickening and hardening of the EPB and APL tendon sheaths in de Quervain's disease is caused by increased synthesis of the extracellular matrix, increased thickness of the collagen fibrils and areas of myxomatous and chondroid metaplasia.
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  • 159
    ISSN: 1432-5195
    Keywords: Nerve graft ; Peripheral nerve injury ; Quantitative histological study ; Nerve Regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a sectionné le nerf péronier commun de 15 rats mâles et ces rats ont été divisés en quatre groupes: (1) greffe immédiate (Groupe I); (2) greffe différée au premier mois (groupe IM); (3) greffe différée au 3ème mois (groupe 3M) tandis que 5 rats indemnes faisaient office de groupe de contrôle. Tous les rats ont été sacrifiés 5 mois après la greffe. Trois indices morphologiques des axones myélinisés ont été évalués: (1) leur nombre moyen par unité de surface, (2) leur diamètre moyen et (3) la densité des axones dans l'ensemble du nerf. Les sites examinés ont été: (1) le segment proximal du nerf sectionné, (2) la greffe et (3) le segment distal du nerf sectionné. Quand la réparation est effectuée tardivement les axones du segment proximal s'atrophient, ce qui indique que le retard perturbe la régénération des axones et réduit l'activité dans le segment distal. La régénération est faible dans le groupe «3 M» comparativement au groupe «I». Cependant la régénération dans le groupe «IM» est identique à celle du groupe «I». Ces résultats démontrent que la greffe secondaire précoce peut être indiquée lorsqu'il n'est pas souhaitable d'effectuer une réparation immédiate.
    Notes: Summary The common peroneal nerves of 15 male rats were severed and the rats were divided into four groups: (1) immediate grafting (I group); (2) grafting delayed one month (IM group); (3) grafting delayed for three months (3M group) and 5 healthy rats were used as controls (control group). All the rats were sacrificed 5 months after grafting. Three morphological indices of the myelinated axons were evaluated, (1) the mean number per unit area, (2) their mean diameter and (3) the axon packing density. The sites examined were, (1) the proximal stump of the recipient nerve, (2) the grafted nerve and (3) the distal stump of the recipient nerve. When repair was carried out late there was atrophy of the axons within the proximal stump, indicating that delay affected axon regeneration as well as resulting in reduced activity in the distal stump. The “3M” group showed poor regeneration in comparison to the “I” group. However, in the “IM” group, the regeneration rate was similar to that of the “IM” group. Our results indicate that early secondary grafting should be considered when circumstances exist which make primary repair undesirable.
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  • 160
    ISSN: 1432-2307
    Keywords: Pigmented adenoma ; Cushing's syndrome ; Lipofuscin ; Ultrastructure ; Steroid analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural and morphometrical analysis of brown pigment in pigmented (black) and non-pigmented adrenocortical adenomas of Cushing's syndrome and non-functioning pigmented adrenocortical nodules was performed in reference to tissue concentrations and in vitro production of steroids by the adenoma tissue. Pigment in pigmented adenomas was of membrane-bound lysosomal nature, while that of pigmented nodules contained membrane-unbound droplets of lipoid character. The morphometrical study showed little difference among individual adenomas. There was no difference between pigmented and non-pigmented adenomas in the amount of production and tissue concentrations of steroids. The steroid concentrations in a pigmented nodule were lower than those in an adenoma of Cushing's syndrome, but not significantly. Discussion is focused on the difference of pigment of lysosomal nature and of lipoid peroxidation.
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  • 161
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    Virchows Archiv 407 (1985), S. 97-105 
    ISSN: 1432-2307
    Keywords: Cardiomyopathy ; Leigh's disease ; Mitochondriopathy ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and postmortem findings in a female infant, suffering from Leigh's disease and cardiomegaly are described. The cardiac enlargement was due to symmetrical thickening of both ventricular walls and the septum. On light microscopy a widespread fibre disarray with a slight predilection for the ventricular septum was observed. Ultrastructural changes included an extreme reduction in the number of myofibrils and an excess of mitochondria. Abnormalities of the mitochondrial structure with tubular and myelinic transformation of the cristae suggested that a mitochondriopathy is responsible for the cardiomegaly in Leigh's disease.
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  • 162
    ISSN: 1432-2307
    Keywords: Normal Human Breast ; Mitosis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study the proliferative (stem?) cells within the parenchyma of the normal “resting” breast were characterised by the ultrastructural examination of 60 mitotic cells. The parenchyma consists of epithelial and myoepithelial cells plus a few intraepithelial lymphocytes and macrophages. The majority of mitotic cells were randomly distributed throughout the lobules with a few present in ducts. In all cases the cells were identified as luminally positioned polarised epithelial cells. The proliferating cells had similar cytoplasmic features and were indistinguishable from adjacent interphase epithelial cells. No evidence was found for the division of subluminal epithelial or myoepithelial cells. These observations would be consistant with a single cell type giving rise to both epithelial and myoepithelial cells.
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  • 163
    ISSN: 1432-2307
    Keywords: Multiple myeloma ; Crystalline deposits ; Ultrastructure ; Image analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 58-year-old man showed bone marrow crystalline structures associated with a lambda light chain producing multiple myeloma. Analysis and processing of electron images clearly displayed the periodic structure of the crystals. Immunochemistry suggested that they contained the whole or a fragmented constant portion of immunoglobulin.
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    Virchows Archiv 408 (1985), S. 1-13 
    ISSN: 1432-2307
    Keywords: Hepatitis, viral, human ; Plasma cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma cells and their precursors were studied by electron microscopy in liver biopsies from 41 patients with acute viral or drug-induced hepatitis. Mature plasma cells showed the ultrastructural features of the reticular or lymphatic type. Blast cells of different types were also observed. Type 1 predominated in classical acute hepatitis, and appears to transform directly into mature plasma cells. Type 2 corresponds to the centroblast of lymphoid tissue. It was found in fully developed hepatitis, especially when necrosis was severe. Type 3 resembled the centrocyte of lymphoid organs; it was seen particularly in viral hepatitis, and only in severe cases with extensive necrosis. The type 4 plasmablast had the ultrastructural characteristics of a plasmacytoid T cell.
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  • 165
    ISSN: 1432-2307
    Keywords: Perisinusoidal cell ; Endothelial cell ; Portacaval anastomosis ; Rat ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Shunting of portal blood in the rat leads to liver atrophy and to an increase in arterial blood flow with microcirculatory disturbances. The aim of this study was to investigate the effects of these disturbances on the liver sinusoidal barrier (endothelial and perisinusoidal cells) using morphometric techniques. Rats with portacaval anastomosis (PCA) and sham operated pair-fed controls were studied 3 months after the shunt. Sinusoidal volume density in PCA increased but not significantly and the volume density (Vv) of total endothelial (EC) and perisinusoidal cells (PSC) increased by 104.54% compared to sham operated pair-fed rats. The increase of EC Vv was not associated with an increase in surface density (Sv) suggesting a fall in the number of small fenestrations and an increase in cell thickness. This interpretation supports the morphological observations. The increase of PSC Vv was mainly related to the increase in their subendothelial processes Vv and not to that of the cell body Vv. Lipids Vv and RER Sv expressed per sinusoidal cells remained unchanged suggesting that the balance between the 2 hypothetical functions of the PSC, namely fibrogenesis and storage of vitamin A, was maintained. In conclusion, changes of EC and PSC after PCA result mainly in thickening of the sinusoidal barrier. This increase may impair exchanges between the sinusoidal lumen and Disse space and contribute to functional abnormalities.
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  • 166
    ISSN: 1432-2307
    Keywords: Oligomeganephronic renal hypoplasia ; Tapetoretinal degeneration ; Ultrastructure ; Focal glomerular sclerosis ; Nephronic reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bilateral renal hypoplasia with oligomeganephronia, associated with bilateral tapetoretinal degeneration was observed in a child; this association has been reported only once before. Light, ultrastructural and immunofluorescent microscopic studies of the renal tissue were performed. The glomeruli were few and hypertrophic, with numerous mesangial cells, mesangial deposits, focal glomerular sclerosis and prominent thickened basement membrane. Two types of tubular changes were observed: focal necrosis of proximal tubules and focal atrophy of tubules surrounded by a thickened basement membrane. Mild fibrosis with few lymphocytes could be observed in the interstitium. A congenital reduction in the number of nephrons, related to a yet unknown pathological process may explain these morphological changes in part.
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  • 167
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    Cell & tissue research 239 (1985), S. 3-8 
    ISSN: 1432-0878
    Keywords: GnRH receptors ; Gonadotropes ; Coated pits ; Internalization ; High-resolution autoradiography ; LHRH, Gonadoliberin ; Pituitary gland ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Localization of GnRH receptors in rat pituitary gonadotropes was studied by use of 125I-[azidobenzoyl-D-Lys6]GnRH which, upon photolysis, is covalently bound to the receptor molecule. Using high resolution autoradiography, it was found that, after a 90-min incubation of the analog with pituitary cells at 4° C, 93% of the silver grains were associated with the plasma membrane of the gonadotropes. After 45-min incubation of the cells at 37° C, clustering and internalization of the receptor-bound GnRH analog were evident. Silver grains were associated with coated pits, intracellular vesicles, Golgi complexes, lysosome-like structures and secretory granules. The data indicate that receptor-bound GnRH agonist is internalized, at least in part, via coated pits and is subsequently routed to lysosomes where degradation of the hormone-receptor complex may occur. The presence of a considerable amount of silver grains associated with secretory granules may suggest that some of the internalized receptor molecules can escape degradation and be recycled to the cell membrane.
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  • 168
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    Cell & tissue research 239 (1985), S. 31-35 
    ISSN: 1432-0878
    Keywords: Lymph filtration ; Antigen and antibody distribution ; Subcapsular sinus ; Lymph node ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A recent study of lymph nodes of the rat showed that they are morphologically and physiologically compartmentalized. A compartment of a node includes a portion of subcapsular sinus into which the lymph, entering via the related afferent lymphatic opening, is filtered. The study also showed that colloidal carbon injected locally in a small dose becomes predominantly associated with the areas of the inner wall of the subcapsular sinus that cover the extrafollicular zone of the peripheral cortex. Little carbon is seen over the folliculo-nodules (follicles with a nodule or germinal center). The question arose as to whether drained natural substances, as antigens and antibodies, follow the same pattern of distribution in the subcapsular sinus as the carbon. Therefore, small doses of fluorescein isothyocyanate (FITC)-conjugated antigens were injected locally into normal rats whose own antibodies in the nodes were stained by immunofluorescence. The pattern of distribution of the antigens in the draining nodes was found to be the same as that of the carbon. Furthermore, the lymph-carried antibodies of the rats were found to follow the same pattern. The morphological basis for such a pattern is explained. The results are further discussed with regard to the probable normal entry route of lymph-carried antigens in the parenchyma of nodes.
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  • 169
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    Cell & tissue research 239 (1985), S. 137-140 
    ISSN: 1432-0878
    Keywords: Lanthanum ; Odontoblasts ; Tight junctions ; Tooth pulp ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Odontoblasts are known to be involved in the process of dentinogenesis but it is not clear whether substances may also be deposited in predentine and dentine by passing between these cells. Although tight junctions have been described, it is not clear if they are macular or “leaky” as opposed to continuous or “tight”. In this study use has been made of the permeability of fenestrated capillaries amongst the odontoblasts to deposit the penetrative tracer lanthanum in the interodontoblastic space. This was done by perfusion of anaesthetized rats with physiological solutions containing lanthanum nitrate at 37° C. Immersion fixation of transverse segments of mandibular incisors and examination with an electron microscope showed that lanthanum could permeate 40–50 μm between the odontoblasts to reach the peripheral pulp. Towards the predentine, often less than 10 μm from the capillaries, its progress was abruptly and completely halted by the junctions at the apical ends of the odontoblast cell bodies. Lanthanum was not found in the predentine. The mature secretory odontoblasts in the rat incisor have therefore been shown to be joined by continuous tight junctions. In the process of dentinogenesis this means that all substances deposited in predentine and dentine must arrive by passing through the odontoblasts.
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  • 170
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    Cell & tissue research 239 (1985), S. 183-188 
    ISSN: 1432-0878
    Keywords: Fenestrations ; Basal lamina ; Intestine, small ; Immune system ; SEM ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Fenestrations of the basal lamina of rat intestinal villi were revealed by scanning electron microscopy after removal of the overlying epithelial cells by osmic acid maceration. These fenestrations are circular to oval in shape and are 0.5 μm to 5 μm in diameter. They are richly distributed at a density of 1–2x104/mm2 in the upper two thirds of the villi, except at the very tips. Roughly 500 fenestrations are found on each side of an average sized tongue-shaped villus. Transmission electron-microscopic observations showed that these fenestrations were passages for migrating cells of the immune system such as lymphocytes, eosinophils and macrophages. Protrusions from the basal parts of epithelial cells were also observed passing through these fenestrations. These findings are discussed with respect to their immunological implications and to the passage of nutrients.
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  • 171
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    Cell & tissue research 239 (1985), S. 293-298 
    ISSN: 1432-0878
    Keywords: Acid phosphatase cytochemistry ; Lysosomes ; Synovial membrane ; Synoviocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The lysosomal system of the two types of synoviocytes (A and S) from the knee joint of normal rat synovial membrane was studied by electron-microscopic acid phosphatase cytochemistry. In random sections of the synovial intima lysosomes were more often encountered in the A-cell profiles than in the S-cell profiles. Characteristically, type-A synoviocytes showed many large and medium-sized lysosomes the cytochemical appearance of which varied considerably. No acid phosphatase activity was detectable in the cisternae of the Golgi apparatus or in the Golgi vesicles. In type-S synoviocytes the lysosomes were smaller, and more uniform in cytochemical appearance. Heavy deposits of acid phosphatase reaction product were constantly demonstrated in cisternae of the Golgi apparatus as well as in smooth-walled Golgi vesicles in type-S cells. The findings that type-A and type-S synoviocytes show distinctly different organization of the lysosomal system indicate that the roles of the lysosomes in these two types of cells may be different.
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  • 172
    ISSN: 1432-0878
    Keywords: Corpora allata ; Ultrastructure ; Juvenile hormone ; Rates of synthesis ; Reproductive cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructure was correlated with rates of juvenile hormone synthesis in corpora allata from females of the viviparous cockroach Diploptera punctata at seven daily intervals during the first vitellogenic cycle. Synthetic activity of the glands was determined by in vitro radiochemical assay before the glands were fixed for electron microscopic analysis. The cycle in rates of juvenile hormone synthesis progressed from about 20 pmol h-1 per gland pair (oocytes 0.60 mm long) to a maximum mean rate of 140 pmol h-1 per pair (oocytes 1.40–1.47 mm long) and declined to about 20 pmol h-1 per pair at ovulation (oocytes about 1.65 mm long). Conspicuous ultrastructural changes occurred with changing synthetic rates. In glands with increasing rates of synthesis, mitochondria showed less electron-dense matrix, greater diameter and more irregular shape. Smooth endoplasmic reticulum changed from easily seen to obscure tubules, networks, and vesicles. Rough endoplasmic reticulum appeared in longer, more curved segments. Newly formed autophagic vacuoles appeared in all glands of highest activity rates. In glands with decreasing rates of synthesis, the mitochondrial matrix became denser, width smaller, and shapes less irregular. Smooth endoplasmic reticulum again appeared tubular and distinct. Golgi complexes were more conspicuous. Rough endoplasmic reticulum in whorls and large numbers of autophagic vacuoles continued to be present.
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  • 173
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    Cell & tissue research 239 (1985), S. 343-347 
    ISSN: 1432-0878
    Keywords: Gastric mucosa ; Surface mucous cell ; Physiological cell loss ; Cell renewal ; Ultrastructure ; Golden hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Fine-structural aspects of physiological cell loss in the gastric mucosa of the golden hamster were observed. As the surface mucous cell ascends along the gastric pit, the cell becomes taller and funnel-like in shape. The interfoveolar cell located at the superficial portion of the gastric pit has many lysosomes and a few lipid droplets in the cytoplasm. The nucleus moves toward the upper region of the cytoplasm, while the Golgi apparatus moves downward toward the infranuclear region. After the rupture of the apical plasma membrane takes place, the lateral and basal plasma membranes of this cell remain in spite of loss of the cell contents. Between the basal plasma membrane of the interfoveolar cell and the capillary endothelium is a thick connective tissue layer characterized by densely packed collagen fibrils. The remaining basal and lateral plasma membranes of the ruptured cell and the thick underlying collagenous layer might play a role in protecting the tissue from potential damage induced by the physiological cell loss.
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  • 174
    ISSN: 1432-0878
    Keywords: Spleen ; Dendritic cells ; Ultrastructure ; Immunization ; Bufo calamita
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the present study comparative aspects of the ultrastructure of the spleen were analyzed in non-immunized and T-dependent antigen-challenged natterjacks, Bufo calamita. Special attention is focused on the role of the non-lymphoid components in the splenic immunoreactivity. Ten days after primary immunization with sheep erythrocytes, splenic lymphoid follicles increase considerably in number and size. By that time, lymphoblasts, medium and large lymphocytes abound in the periphery of the white pulp near the marginal zone. Meanwhile, in the red pulp numerous monocytes migrating across the sinusoidal walls apparently transform into giant, dendritic-like cells. Twenty days after immunization the splenic lymphoid follicles decrease in number, although certain reactivity persists and numerous plasma cells occur in the cell cords and sinusoids of the red pulp. These results are discussed comparatively with those reported in other lower vertebrates.
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  • 175
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    Cell & tissue research 239 (1985), S. 651-655 
    ISSN: 1432-0878
    Keywords: Gap junctions ; cAMP ; Liver ; Freeze-fracturing ; Morphometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Since cAMP has recently been reported to be a possible physiological modulator of cell-to-cell communication, we performed a quantitative freeze-fracture investigation on the hepatocyte gap junctions after administration of a membrane-permeant derivative of this cyclic nucleotide. For this purpose, male rats received two intraperitoneal injections of 100 mg dibutyryl cAMP/kg body weight with a time interval of 2.5 h. Litter mates were injected with saline only. Five hours after the start of the treatment, tissue blocks of the left lateral liver lobe were fixed by immersion and processed for freeze-fracture. By point counting on negatives projected on a square double-lattice test system the relative gap junctional area on contiguous hepatocyte membranes was determined. As compared to control animals, the proportion of the membrane area occupied by gap junctions in dibutyryl cAMP-treated liver parenchyma significantly increased from 4.9% to 6.1%. Within the gap junctions no changes in shape, particle density or packing pattern were observed. Possibly, the enlarged gap junctional area provides structural pathways for the integration of the response of hepatocytes to messages mediated by cAMP.
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  • 176
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    Cell & tissue research 239 (1985), S. 131-136 
    ISSN: 1432-0878
    Keywords: Capillary permeability ; Lanthanum ; Peripheral nerves ; Tooth pulp ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Experiments were performed to compare the permeability of capillaries supplying the endoneurial environment, which is invested by perineurium, with vascular permeability in the pulp where perineurium is absent. Anaesthetised rats were perfused through the aorta with physiological solutions containing lanthanum nitrate at 37° C. Pieces of inferior alveolar nerve and segments of mandibular incisors were immersion-fixed and transverse sections were examined electron microscopically for the distribution of lanthanum. In the pulp the nerve fibres pass between lanthanum-impermeable arterioles and venules en route to the incisal end. In the peripheral pulp a few capillaries were permeable but the most permeable capillaries lay between the odontoblasts. Pulpal capillary permeability was attributed to the fenestrated endothelium and contrasted with the unfenestrated endoneurial capillaries which were impermeable to lanthanum. Whereas the tight junctions of endoneurial capillaries are known to prevent certain blood-borne substances from entering the endoneurium, it was not clear whether the permeability of the pulpal capillaries, which are distant from the nerve fibres, could affect the nerve fibre environment. No extravasated lanthanum reached the pulpal nerve fibres suggesting that they are not affected. Technically it was not possible to examine the incisal third of the tooth where the situation could be different because the volume of the pulp decreases and capillaries lie closer to the nerve fibres.
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  • 177
    ISSN: 1432-0878
    Keywords: Neuropeptides ; Autonomic denervation ; Neuropeptide Y ; Vasoactive intestinal polypeptide (VIP) ; Substance P ; Urinary bladder ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The origin and distribution in the urinary bladder of nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and substance P (SP) were investigated in rats. Experimental procedures comprised preganglionic decentralization or postganglionic denervation of the bladder and also chemical sympathectomy as well as capsaicin treatment of newborn rats. Nerve fibers containing NPY were richly distributed in the detrusor muscle and also in the pelvic ganglia. Numerous NPY-containing nerve cell bodies were found in pelvic ganglia. A rich occurrence of VIP fibers and a more sparse distribution of SP-containing fibers were also found in the bladder as well as a relatively rich representation of VIP- containing nerve cell bodies in the pelvic ganglia. After decentralization the intensity of VIP and NPY immunofluorescence increased in nerve cell bodies of the pelvic ganglia and in nerve fibers in the wall of the bladder. Postganglionic denervation, on the other hand, eliminated all peptides examined in the bladder wall. After postganglionic denervation the situation in the ganglia was approximately the same as after decentralization. Chemical sympathectomy (6-OHDA) did not seem to change significantly the frequency and distribution of VIP-, SP- and NPY-fibers in the muscle layer of the bladder or in the pelvic ganglia, while the NPY-containing nerve fibers in the submucosal layer and around blood vessels of the bladder disappeared. Adrenergic nerve fibers in the wall of the bladder (visualized by histofluorescence) were markedly reduced in number after administration of 6-OHDA. Capsaicin-treatment of newborn rats caused a loss of SP-fibers in the wall of the bladder, supporting the view that these fibers are sensory in nature in the urinary bladder. Although it cannot be entirely excluded that NPY-containing fibers in the wall of the bladder are adrenergic, the present results suggest that the NPY-fibers as well as the VIP-fibers of the bladder wall originate mainly in non-adrenergic cell bodies of the pelvic ganglia. However, perivascular NPY-containing nerve fibers are adrenergic in nature.
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  • 178
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    Cell & tissue research 239 (1985), S. 177-182 
    ISSN: 1432-0878
    Keywords: Lymphoid tissue ; Lung ; Bronchi ; Immuno-histochemistry ; Enzyme histochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunohistochemical, enzyme-histochemical and electron-microscopical methods were used to study non-lymphoid cells of control and stimulated rat bronchus associated lymphoid tissue (BALT) in situ and in suspensions. Particular attention was paid to the so-called antigenhandling cells, i.e., the interdigitating cells (IDC), which are situated in the T-cell areas, the follicular dendritic cells (FDC), which appear to be restricted to germinal centers, and macrophages, present both in T-cell and B-cell areas. The interdigitating cells were distinguished by being Ia-positive and by the presence of acid phosphatase and non-specific esterase activity in an area near the nucleus. Follicular dendritic cells could be observed in situ by using a monoclonal antibody and by the in vitro trapping of HRP-anti-HRP complexes. Several types of macrophages were found. At the electron-microscopical level no well-developed IDC and FDC could be detected in control BALT. However, in BALT of lipopolysaccharide-stimulated and mycoplasma-infected rats, well-developed IDC and FDC were found. It can be concluded that IDC's and FDC's can be found in BALT.
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  • 179
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    Cell & tissue research 239 (1985), S. 405-415 
    ISSN: 1432-0878
    Keywords: Testis ; Leydig cell ; FSH ; Morphometry ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of FSH on the testicular interstitial tissue of immature hypophysectomized rats were studied by comparing morphological changes in Leydig cells with quantitative changes in interstitial tissue histology using morphometric analysis. Three groups of rats received subcutaneous injections of 0.5 ml saline vehicle or 10 μg rFSH or 20 ng oLH (equivalent to the amount of LH known to contaminate the FSH), twice daily for 7 days. Administration of FSH significantly increased testis weight and stimulated more advanced spermatogenesis compared to saline or LH. Morphometric analysis of testes of LH-treated rats showed a small but significant increase in total interstitial cell volume compared to saline treatment. FSH caused much greater increases in the total volume of interstitial tissue and interstitial cells than either saline or LH and significantly increased the total volume of interstitial fluid by comparison with the other groups. FSH but not saline or LH treatment resulted in a striking hypertrophy of Leydig cells, to produce cells ultrastructurally identical to Leydig cells from adults. Since the target tissue of FSH is the seminiferous epithelium, the observed effects on Leydig cells by FSH treatment suggest that the secretion of factors by the seminiferous tubules may mediate the maturation of Leydig cells.
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  • 180
    ISSN: 1432-0878
    Keywords: Nerve ending ; Tadpole tail ; Ultrastructure ; Acetylcholinesterase ; Metamorphosis ; Rana japonica ; R. catesbeiana
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In anuran tadpole tails, the myelinated motor nerve fibers branch in the myoseptum to innervate both red and white muscle fibers at, or near, their ends. There are no significant ultrastructural differences between the nerve endings of the two types of muscle fibers. Intense acetylcholinesterase reaction product was observed in synaptic clefts and junctional folds, as well as in transverse tubules. As metamorphosis proceeded, the junctional folds of the nerve endings disappeared, however, acetylcholinesterase reaction product was still observed in the synaptic clefts. As muscle fibers began to degenerate, nerve endings began to separate from them. However, after nerve endings were completely separated from the surfaces, degenerated muscle fibers, synaptic and cored vesicles were still well preserved although no acetylcholinesterase reaction product was found. It seems clear that the mechanism of the muscle degeneration in the tadpole tail during metamorphosis is not the result of the degeneration of its nerve endings.
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  • 181
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    Keywords: Trachea ; Basal lamina ; Anchoring fibril ; Ruthenium red-positive filaments ; New anchoring device ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The structural relationship between the basal lamina and the underlying reticular tissue was studied, with special attention to the relationship among basal lamina-associated anchoring fibrillar (AF) arcs (Kawanami et al. 1978, 1979) and other fibrillar components, in the epithelium-denuded trachea of the rat. Quantitative analysis of a large number of AF arcs reveals that the majority of the AF arcs has no other fibrillar components of passage. This suggests that most AF arcs do not serve as a real anchoring device, connecting the basal lamina with the underlying reticular tissue, as has so far been suggested by Kawanami et al. (1978). Ruthenium-red staining reveals the presence of a unique meshwork of microthread-like filaments connecting the undersurface of the basal lamina or the AF arcs with the underlying fibrillar components with a remarkable continuity, suggesting that the filaments act as a real anchoring device; these filaments link, instead of the AF arcs, the basal lamina, to the subjacent reticular tissue. Various enzymatic treatments of the filaments indicate that their chemical nature is probably non-collagenous (glyco)protein without glycosaminoglycan moieties.
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  • 182
    ISSN: 1432-0878
    Keywords: Synapses ; Intestinal nerve ; Ultrastructure ; Helix pomatia ; Horseradish peroxidase technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of nerve cells and the finestructural organization of synaptic contacts have been investigated in the intestinal nerve in the snail Helix pomatia. Three types of nerve cells, occurring singly or in groups, can be distinguished on the basis of the ultrastructure of their perikaryon and content of granules. The peripheral output of these nerve cells has been verified by retrograde CoCl2 and NiCl2 staining. Both axosomatic and axo-axonic specialized synaptic contacts occur in the intestinal nerve. Presynaptic elements of these synaptic contacts contain 100–120 nm granular vesicles or 120–200 nm neurosecretory-like granules. Following intracellular horseradish peroxidase (HRP) labelling of identified central neurons responsible for peripheral regulatory processes, several labelled axons running toward the periphery can be followed throughout the branches of the intestinal nerve. These labelled axon processes (either primary axon or small collaterals) form specialized synaptic contacts, inside the intestinal nerve, and are always in a postsynaptic position. The occurrence of peripheral axo-somatic and axo-axonic synapses provides a morphological basis for integrative processes taking place in the intestinal nerve (peripheral nervous system) of Helix pomatia.
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  • 183
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    Cell & tissue research 239 (1985), S. 37-42 
    ISSN: 1432-0878
    Keywords: Subcapsular sinus ; Subsinus layer ; Peripheral cortex ; Lymph node ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The peripheral cortex of a lymph node consists of folliculo-nodules (follicles with a nodule or germinal center) and an extrafollicular zone. In the course of an analysis of the nodes in rats under various experimental or abnormal conditions, our attention became focused on the particularities of a thin layer of peripheral cortex underlying the subcapsular sinus. The present paper reports on observations which led to the identification of the “subsinus layer” of the peripheral cortex. The observations suggest that this layer complements the activity of the inner wall of the subcapsular sinus. The layer probably contributes to the selection of certain elements from the afferent lymph and guides them towards the node area where they can join the cell population involved in the immunological activity in which they are to participate.
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  • 184
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    Keywords: Pancreatic acini ; Secretion ; Amylase ; Secretagogues ; Receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Incubation of rat pancreatic lobules for 90 min with optimal concentrations of caerulein, carbachol or secretin caused the release of about 30% of the amylase content. Combination of secretin with carbachol or caerulein increased the amylase output to about 40%. With secretin, as with carbachol or caerulein, heterogeneity of cellular responsiveness was observed, some acini being partially or completely depleted of their zymogen granules, whereas others appeared to be resting. When secretin was combined with carbachol or caerulein, granule depletion, originally confined to small groups of neighbouring acini, spread to form large areas of degranulated cells, sometimes comprising a whole section of a lobule. In dispersed acini, under the same conditions, carbachol caused the release of about 60% of the amylase content, and secretin 40%. When both secretagogues were combined, a significant increase to 78% was observed. Under these conditions, there was some important cellular damage, as indicated by the release of 20% of the amylase content and between 6 and 12% of lactate dehydrogenase into the media, in the absence of stimulus. These results were corroborated by cytological observations. On the basis of their secretory response two groups of acini can be distinguished, those that respond to carbachol, caerulein or secretin and those that respond to the combination of secretin with carbachol or caerulein. Electrophoretic patterns of secretory proteins released by lobules stimulated by these different types of secretagogues were essentially similar. The pattern was quite different, however, in the absence of a stimulus. The most striking feature was the presence of a band at 63 Kd whereas a 73.5 Kd band was found only under conditions of stimulation. The latter results support the view that under resting and stimulated conditions secretory proteins are released from distinct compartments in the acinar cell.
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  • 185
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    Cell & tissue research 239 (1985), S. 229-233 
    ISSN: 1432-0878
    Keywords: Chemotherapy ; Vincristine ; Constipation ; Mucosa ; Regulatory peptides ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The microtubule-disrupting drug vincristine is a common component of anti-cancer chemotherapeutic regimes, which produces acute constipation as a side effect. Although generally attributed to damage to the myenteric plexus, the precise mechanism of this disturbance is unknown. In addition, vincristine causes marked aberrations in the secretory response of pancreatic endocrine tissue in both man and rats. No information is available on its possible effect on regulatory peptides of the gastrointestinal tract. In this study we have produced vincristine-induced constipation in rats at a dosage comparable with that employed in the treatment of human subjects. Immunocytochemistry revealed concomitant disturbances in cells exhibiting immunoreactivity for gastrin in the antrum, for gastric inhibitory polypeptide and 5-hydroxytryptamine in the duodenum, for enteroglucagon in the colon, and for somatostatin in all three sites. These widespread effects are transient in nature with normal cell numbers and morphology being reestablished within 6 days. It is suggested that the observed effects are a direct result of microtubule disruption and that gastrointestinal regulatory peptide and amine immunoreactive cells have a rapid regeneration potential.
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    Cell & tissue research 239 (1985), S. 235-239 
    ISSN: 1432-0878
    Keywords: Erythropoiesis ; Autophagy ; Mitochondria ; Electron microscopy ; Stereology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Late erythroblasts and reticulocytes from bone marrow of male Wistar rats were studied by electron-microscopic stereology. Late erythroblasts with morphological signs of nuclear extrusion (EN+erythroblasts) and late erythroblasts without these signs (EN-erythroblasts) were analysed separately. The volumes of mitochondria, autophagosomes, autophagocytosed mitochondria, autophagocytosed cytoplasm and degraded material inside autophagosomes were calculated per unit volume of cytoplasm. The results demonstrate that (1) the volume density of mitochondria in the cytoplasm decreases by 34% during maturation from (EN-)- to (EN+)-erythroblasts (p〈 0.001) and by 60% during differentiation from (EN+)-erythroblasts to reticulocytes (p〈0.001), (2) a fivefold increase in the volume density of autophagosomes in the cytoplasm is noted during maturation from (EN-)- to (EN+)-erythroblasts (p〈0.01), whereas the value of this parameter remains essentially unchanged during the subsequent differentiation to reticulocytes, (3) no mitochondria are found inside autophagosomes of (EN-)-erythroblasts, whereas mitochondria occupy 26% and 35%, respectively, of the autophagosomal volume in (EN+)-erythroblasts and in reticulocytes. Our results show that autophagocytosis of mitochondria starts at the moment of nuclear extrusion and continues in the bone marrow reticulocytes.
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  • 187
    ISSN: 1432-0878
    Keywords: Steroid cell ; Ultrastructure ; Steroidogenesis ; Intersexual fish ; Monopterus albus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural and biosynthetic characteristics of the steroid cells in the gonad of Monopterus albus have been studied. Ultrastructural features related to steroidogenesis have been identified in the interstitial Leydig cells, Sertoli cells, granulosa cells and thecal cells, and are especially abundant in the Leydig cells during the mid-intersexual phase. Steroidogenic ultrastructures in the Sertoli cells develop only during the maturation of the spermatogenic cysts, whereas in the granulosa and thecal cells, these features become obvious only during the maturation of the large oocytes. EM evidence also suggests a nutritive function for the Sertoli cells and the granulosa cells. Results of in vitro steroidogenic studies, using either testosterone or progesterone as a precursor, show a predominant conversion to androstenedione and 5α-reduced compounds, and suggest a change in biosynthesis from 5α-reduced products to androstenedione during sex reversal. 11-Ketotestosterone (11KT) has been identified, but not 11 β-hydroxytestosterone. Production of 11 KT is high in the late intersexual and the male phases, but a lack of a marked variation in 11KT production between the early and the mid-intersexual phase suggests that this steroid is not a trigger for natural sex reversal in Monopterus.
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  • 188
    ISSN: 1432-0878
    Keywords: Development ; Sea urchin ; Hyaline layer ; Granular layer ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Employing electron-microscopic methods that help retain polyanionic materials, we describe the extracellular coverings of a sea urchin (Lytechinus variegatus) throughout ontogeny. The surface of the embryo is covered by a two-layered cuticle (commonly called the hyaline layer), which in turn is covered by a granular layer. The granular layer is retained after addition of alcian blue to the fixative solutions, and has not been previously described for any sea urchin. After hatching, the granular layer disappears, but the hyaline layer continues to cover most of the larval surface until settlement and metamorphosis. A few days before metamorphosis, the hyaline layer lining the vestibular invagination of the competent pluteus larva is replaced by a three-layered cuticle resembling that of the adult sea urchin. The hyaline layer covering the rest of the larva is evidently lost at metamorphosis during the involution of the general epidermis.
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  • 189
    ISSN: 1432-0878
    Keywords: Endochondral bone development ; Osteoblast ; Osteoclast ; Horseradish peroxidase ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To investigate the mechanisms whereby bone cells absorb organic bone-matrix components during endochondral bone development, rat humeri were examined, employing horseradish peroxidase as a soluble protein tracer. Intravenously-injected peroxidase filled the osteoid layer and penetrated into the osteocyte lacunae and canaliculi, but did not enter the mineralized bone matrix. Whereas osteocytes rarely took up exogenous peroxidase, osteoblasts and osteoclasts actively endocytosed peroxidase in pinocytotic coated vesicles, tubular structures, and vacuoles. They also formed endocytotic vacuoles containing peroxidase in the Golgi area. The Golgi apparatus and dense bodies of these bone cells were, however, free of reaction products. Osteoclast ruffled borders were responsible for peroxidase absorption. In the osteoblast, osteocyte and osteoclast, endogenous peroxidatic reaction was detected only in mitochondria and not in other membrane-bounded vesicles and bodies. These results strongly suggest that both osteoblasts and osteoclasts participate in the resorption of bone-matrix organic components during bone remodelling.
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  • 190
    ISSN: 1432-0878
    Keywords: Thyroidectomy ; Cerebellum ; Coated pit ; Mossy fiber terminal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The influence that thyroid hormones have on the development of the cerebellar cortex is well known. Their absence in adults leads to important functional changes probably related to abnormalities in nerve terminal activity, although no morphological alterations have hitherto been described. Using ultrastructural morphometric methods, we have studied the effects of thyroidectomy on the cerebellar cortex mossy fiber terminals of adult rats with different survival periods. No significant changes in the volume and surface area of these terminals were found. The numbers of synaptic vesicles in groups 7, 15 and 30 days after thyroidectomy were significantly greater than in controls. A significant increase in coated pit formation was found when thyroidectomized groups were compared with controls. This increase is due to the lack of thyroxin since it can be counteracted by thyroxin administration. Whether this increased coated pit formation is a membrane retrieval mechanism or is related to the uptake of extracellular molecules remains to be determined.
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  • 191
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    Cell & tissue research 239 (1985), S. 693-701 
    ISSN: 1432-0878
    Keywords: Macrophage ; Bone marrow culture ; Heterogeneity ; Ultrastructure ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of macrophages in culture from mouse bone marrow was followed for 14 days by light and electron microscopy, ultrastructural cytochemistry, and flow cytometric analysis. By 10 days greater than 97% of the cells in culture were mononuclear phagocytes, and by 12 days greater than 99% were identifiable as macrophages. Ultrastructurally, three subpopulations of mononuclear phagocytes were distinguished based on the appearance of cytoplasmic structures. Early in culture, cells containing large, membrane-bounded vesicles predominated. With increasing time in culture these cells were replaced to varying degrees first by cells that contained vesicles filled with relatively dense, osmiophilic material and, finally, by macrophages that contained granules of various sizes, shapes and staining densities. Cytochemical (peroxidase and acid phosphatase) and colloidal gold uptake studies at the ultrastructural level suggested that many, if not all, of these cytoplasmic structures arose by pinocytosis and subsequent fusion of pinocytic vesicles with lysosomes. Analysis of DNA content of propidium iodide-stained nuclei by flow cytometry, coupled with the examination of cells treated with colchicine to arrest mitosis in metaphase, suggested that cell cycling was a negligible contributor to heterogeneity within cultured populations. Thus, by waiting until 12–14 days after bone marrow cultures were initiated, with partial replenishment of the culture medium at 7 days, heterogeneity could be greatly reduced in cultured macrophage populations. Taking this fact into consideration could help to reduce the variability seen in functional studies of macrophage populations that are less homogeneous.
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  • 192
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    Cell & tissue research 240 (1985), S. 233-242 
    ISSN: 1432-0878
    Keywords: Lymphoid tissue ; Tonsilla lingualis ; Ultrastructure ; B- and T-lymphocytes ; Macaca fascicularis (Primates, Cercopithecoidea)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Lymphoid organs are highly organized structures made up of different tissue compartments, each with its own specific cell populations. However, the cellular elements of the lingual tonsil, which forms a significant part of Waldeyer's pharyngeal ring, are not yet documented. This study, therefore, describes the fine structure and tissue organization of tonsilla lingualis in Macaca fascicularis. Ten selected crypto-lymphatic units originating from five perfusion-fixed animals were analysed ultrastructurally. Based on the fine-structural elements contained within, the lymphoid tissue of tonsillar units could be subdivided into follicular (germinal centre) and parafollicular areas. The latter contained predominantly small lymphocytes, lymphoblasts resembling T-blasts, plasma cells, macrophages, occasional neutrophils and many reticular cells resembling fibroblasts. A distinct feature of the parafollicular area was the presence of numerous high endothelial (HEV)or postcapillary venules (PCV). The follicular areas contained many small and large lymphoid cells, mitotic cells, plasmablasts, macrophages and specialised reticular cells resembling follicular dendritic cells (FDC) with distinct desmosomal junctions. These observations show that the crypto-lymphatic units of the lingual tonsil are, in fact, organised into distinct B- and T-cell compartments with their own specific lymphoid and accessory cells.
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  • 193
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    Cell & tissue research 240 (1985), S. 223-232 
    ISSN: 1432-0878
    Keywords: Oral mucosa, simian ; Local mucosal immunity ; Minor salivary glands ; Duct/lymphoid follicle assemblies ; Ultrastructure ; Macaca fascicularis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous light-microscopic and ultra-immunohistochemical tracer studies revealed the existence of an independent local immune response of the simian oral mucosa. This local response is attributed to the presence of minor salivary gland (MSG) duct-related lymphoid tissue. Semithin sections from a total of 263 Epon-embedded tissue blocks from the labial and buccal mucosae of seven monkeys, Macaca fascicularis, were analysed light-microscopically, and 10 suitable MSG duct/follicle assemblies were investigated ultrastructurally. These duct/follicle assemblies include follicular and parafollicular compartments with distinct fine-structural elements. The follicular area or germinal centre contains numerous small and large lymphoid cells, mitotic figures, plasmablasts, macrophages, and cells resembling the follicular dendritic cells with distinct desmosomal junctions. The parafollicular area, which includes the heavily infiltrated duct wall, contains numerous small lymphocytes, T-lymphoblasts, plasma cells and reticular cells resembling fibroblasts. A distinct feature of this compartment is the presence of high endothelial venules (HEV). The presence of HEV and numerous blast cells, resembling blast-forming T-lymphocytes activated in vitro, in a specific area of the duct/follicle assembly strongly suggests that this area is structurally and physiologically identical to the thymus-dependent area of other lymphoid tissues. In other words, the duct/follicle assemblies of simian MSG contain the various specific fine-structural elements that are suitable for antigen recognition and processing. These elements are distributed in discrete compartments comparable to the B- and T-cell areas of “classical” lymphoid tissue.
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  • 194
    ISSN: 1432-0878
    Keywords: Heart ; Mitochondria ; Perfusion ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Mitochondria isolated from heart tissue after a 1-min perfusion with Hanks medium were found to have significantly lower rates of State-3 respiration and respiratory control ratios compared to mitochondria isolated from non-perfused hearts. Examination of the mitochondrial preparations by electron microscopy revealed that a large proportion of the mitochondria isolated from perfused heart tissue were swollen and broken compared to mitochondria from non-perfused hearts.
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  • 195
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    Cell & tissue research 240 (1985), S. 417-423 
    ISSN: 1432-0878
    Keywords: Cysteine protease ; Epidermal cells ; Antigen localization ; Cell differentiation ; Antigen distribution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Monospecific antibody directed to cysteine protease of 2-day-old rat epidermis recently characterized as being different from the proteases previously reported was produced in rabbits. By immunofluorescence microscopy and immunoperoxidase staining with an avidin-biotin-peroxidase method the protease was found to be present in the epidermis of rodents of different ages as well as that of humans, but not in the dermis. The staining in germinative cells was more intense than in cells in the superficial layers. It appeared as irregular patches in the nuclei and stained more diffusely in the cytoplasm where small granular components, strongly stained, were identified. The staining patterns in granular cells showed accumulation of the antigen in a granular form. The morphology and distribution of granules resembled those of keratohyalin-like granules in the nucleus and dense homogenous deposits in the cytoplasm. In cornified cells the reaction product was localized by the plasma membrane where concentration of the dense homogenous deposits occurred, suggesting that the cysteine protease is one component of the unique and characteristic structure of differentiated keratinocytes. In addition, the cysteine protease antigen having the same molecular weight as the epidermal enzyme was detected in liver, kidney and lung indicating a wider tissue distribution of the protease. The significance of the protease in regulation of cellular functions remains to be investigated.
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  • 196
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    Cell & tissue research 240 (1985), S. 641-648 
    ISSN: 1432-0878
    Keywords: Retinal pigment epithelium ; Myeloid bodies ; Ultrastructure ; Lipid metabolism ; Endoplasmic reticulum ; Cytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary It has been suggested (Yorke and Dickson 1984) that myeloid bodies (MBs) in the retinal pigment epithelium (RPE) of the newt, Notophthalmus viridescens, may represent areas of endoplasmic reticulum where lipids, such as 11-cis retinal derived from phagocytized outer segment tips, accumulate prior to esterification. Experiments in which an artificial ester substrate was added during in-vitro incubations have shown that esterase activity is represented in all areas of the newt RPE endoplasmic reticulum, including sites adjacent to all MBs. In related tests in which the localization of enzyme activity was restricted to areas of the cell where there had been accumulations of naturally-occurring (endogenous) esters, the products of ester hydrolysis were restricted to profiles of endoplasmic reticulum associated with lipid droplets, and with the interior of about 20% of those MBs that appeared completely circular in sections. This enzyme activity was not associated with other MB configurations. Results from endogenous-ester hydrolysis were identical to those obtained after staining with ZIO. This ZIO-reactivity was not affected by pre-incubation with agents that blocked or protected sulphydryl groups, and ZIO-reactive sites associated with MBs did not form complexes with digitonin. These observations suggest that MBs are a site of lipid-ester formation, but that they do not represent unique intracellular areas for this activity.
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  • 197
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    Cell & tissue research 241 (1985), S. 1-8 
    ISSN: 1432-0878
    Keywords: Pituitary gland, pars intermedia ; Reserpine ; Secretory granules ; α-MSH ; β-Endorphin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Reserpine has a stimulatory effect on the pars intermedia of the rat pituitary, probably mediated by its action on regulatory catecholaminergic nerves. The effect of single intraperitoneal injections of 0.1–20 mg/kg b.w. of reserpine was studied in adult male rats. Reserpine at a dose of 2 mg/kg b.w. induced degranulation, orientation of the secretory granules along the cell membrane and loss of formaldehyde-chloral-induced fluorescence, accompanied by an activation of the granular endoplasmic reticulum and the Golgi apparatus. With higher doses progressive degranulation and loss of fluorescence were observed. The effect was, however, heterogeneous, and with all doses cells displaying normal ultrastructure and normal fluorescence were regularly present. To study the release of granular products (containing a different components of the pro-opiomelanocortin chain) from individual cells, formaldehyde-chloral induced fluorescence and α-MSH- and β-endorphin immunoreactivies were demonstrated in consecutive sections from pituitaries of rats given 8 mg/kg body weight of reserpine 24 h before sacrifice. The results indicate coordinated release of these granular products at the cellular level after reserpine treatment.
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  • 198
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    Cell & tissue research 240 (1985), S. 49-55 
    ISSN: 1432-0878
    Keywords: Lymph node ; Reticular cell ; Mast cell granule ; Fibronectin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Granules released from mast cells were examined by electron microscopy in regional lymph nodes of rats after the injection of a large dose of horseradish peroxidase (HRP). Thirty minutes after the injection, a large number of mast-cell granules were present in sinuses, most of which adhered to the surfaces of reticular cells and some to macrophages. Two hours after the injection, a number of granules had been taken up by both reticular cells and macrophages. Reticular cells took up more granules than macrophages. Twenty-four hours after the injection, granules were scarce in both types of cells and in the extracellular space. Reticular cells surely participate in dealing with released mast-cell granules in the lymph node. Fibronectin bound to all mastcell granules was demonstrated by immunohistochemistry. Fibronectin probably enables negatively charged mast-cell granules to approach negatively charged cell surfaces to be taken up by both reticular cells and macrophages.
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  • 199
    ISSN: 1432-0878
    Keywords: Macrophage activation ; Pseudomonas aeruginosa ; X-ray microanalysis ; Elemental analysis ; Electrolytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Electron probe X-ray microanalysis (XRMA) of freeze-dried ultrathin sections provides the capability of measuring intracellular elemental content. This methodology was used to investigate the stimulus-permeability coupling responses associated with phagocytosis of Pseudomonas aeruginosa by cultured pulmonary alveolar macrophages (PAMs) of rats. PAMs were challenged with P. aeruginosa suspended in Gey's buffer at a bacteria to PAM ratio of 50∶1 for 1 h at 37° C. A 1-mm3 pellet of the unchallenged control PAMs, challenged PAMs and P. aeruginosa alone was quench-frozen in nitrogen-cooled, liquid propane, and 0.1-μm cryosections were cut at -100° C. X-ray spectra were collected for nucleus and cytoplasm of 39 control PAMs, 36 challenged PAMs and 40 P. aeruginosa. Concentrations (mmole/kg dry weight) were obtained for Na, Cl, K, Ca, Mg, P, S for each cell. In the control PAMs, the content was similar to other mammalian cells. Moreover, there were no differences in elemental content between nucleus and cytoplasm. In the challenged PAMs, Na concentration was 4 times that of control PAMs (p〈0.001) whereas Cl was double (p〈0.001), K was 29% lower (p〈0.001), and Ca was 4 times higher (p〈0.05). The elemental concentration profile in the P. aeruginosa was distinctly different from that of the PAMs: higher Na, Ca, Mg, but lower Cl and K values. These results demonstrate elemental content changes in cultured PAMs challenged with P. aeruginosa that indicate a stimulus-permeability response by membranes associated with the phagocytic process.
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  • 200
    ISSN: 1432-0878
    Keywords: Non-ciliated tracheal cell ; Smooth endoplasmic reticulum ; Ultrastructure ; Cytochrome P-450 ; Immunohistochemistry ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Non-ciliated SER-rich cells of the tracheal epithelium of normal, phenobarbital-treated and 3-methylcholanthrene-treated mice were studied ultrastructurally and immunohistochemically. The apical portion of these cells protrudes into the tracheal lumen, especially in the mice treated with the two compounds, and the apical cytoplasm is filled with numerous tubular elements of SER. Besides, the non-ciliated cells of 3-methylcholanthrene-treated mice show a strong positive reaction to the antiserum against microsomal cytochrome P-450 of liver. These findings support the concept that the non-ciliated tracheal cell may be involved in the metabolism of endogeneous and exogeneous chemical compounds.
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