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  • Articles: DFG German National Licenses  (1,104)
  • 1995-1999  (1,104)
  • 1996  (1,104)
  • Engineering General  (686)
  • Industrial Chemistry and Chemical Engineering  (246)
  • Nuclear reactions
  • Rat
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  • Articles: DFG German National Licenses  (1,104)
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Years
  • 1995-1999  (1,104)
Year
  • 101
    ISSN: 1432-1106
    Keywords: Malnutrition ; Hippocampus ; Dendrites ; Degeneration ; Regrowth ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently shown that lengthy periods of low-protein feeding of the adult rat lead to deficits in the number of hippocampal granule and pyramidal cells, and in the number of mossy fiber synapses. These findings prompted us to analyze the dendrites of these neurons to evaluate whether, under the same experimental conditions, degenerative and/or plastic changes also take place at the dendritic level. The hippocampal formations from five 8-month-old rats fed a low-protein diet (casein 8%) for 6 months from the age of 2 months and from five age-matched controls were Golgi-impregnated and the morphology of the dendritic trees quantitatively studied. We found that in malnourished animals there was a reduction in the number of dendritic branches in the dentate granule cells and in the apical dendritic arborizations of CA3 pyramidal neurons. In addition, in the dentate granule cells the spine density was markedly increased and the terminal dendritic segments were elongated in malnourished animals. No alterations were found in the apical dendrites of CA1 pyramidal cells. The results obtained show that long periods of malnutrition induce marked, although not uniform, changes in the dendritic domain of the hippocampal neurons, which reflect the presence of both degenerating and regrowing mechanisms. These alterations are likely to affect the connectivity pattern of the hippocampal formation and, hence, the activity of the neuronal circuitries in which this region of the brain is involved.
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  • 102
    ISSN: 1432-1106
    Keywords: Transplantation immunology ; Spinal cord ; Cortex ; Ramified and reactive microglia ; Intraocular ; transplantation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While the central nervous system (CNS) has been characterized as an immunologically privileged site, there are also several reports describing immunological reactions within the CNS. A certain degree of immunological privilege has also been ascribed to the anterior chamber of the eye. We have used the intraocular transplantation model to study immunological reactions in transplants of embryonic neural tissue. Outbred SpragueDawley rats and inbred Fisher rats were used. Pieces of rat parietal cortex or the cervical spinal cord were prepared from embryonic day 14 and implanted into the eye chambers of adult rats of the same strain. Following intraocular maturation, grafts were analysed using antibodies against: major histocompatibility complex (MHC) class I, MHC class II; rat antigens CD4, CD8, CD11b; T-cell receptor; rat antigen ED1; and glial fibrillary acidic protein. Using this set of markers for immunological reactions, transplants were scored on a blind basis. We found no significant differences in immunological scores between transplants obtained from different litters of fetuses of the outbred animals. Grafting in the outbred strain led to increased numbers of immunologically reactive cells in the grafts. This was not seen in grafts in the inbred strain. Spinal cord transplants led to a significantly higher degree of cytotoxic immunity-related cells expressing MHC class II as well as CD4-positive cells. There was a positive correlation between ED1 negativity and well-developed ramified microglia. From these results we conclude also that well-developed intraocular CNS tissue grafts do contain cellular evidence of immunological events and that different areas of the CNS may provoke different degrees of response. Reactive microglial proliferation appears to be one of the most sensitive ways to monitor the immunological condition of grafted CNS tissue.
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  • 103
    ISSN: 1432-1106
    Keywords: Glutamate receptor ; Cerebral cortex ; White matter ; Electron microscopy ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution of the [3H]alpha-amino-3-hydroxy-5-methylisoxzalepropionic acid (AMPA) receptor subunit GluR4 was studied in frontal, parietal and temporal cerebral cortex, subcortical white matter and corpus callosum of neonatal, immature and mature rats. In 1-to 2-day-old rats, a few oligodendrocyte progenitors and amoeboid microglia in the supraventricular part of the corpus callosum were immunolabelled for GluR4. At 7 to 10 days, the number of amoeboid microglia and oligodendrocyte progenitors in white matter increased; many neurons in cortex, including pyramidal neurons, were also moderately labelled for GluR4. The pattern of GluR4 immunostaining in 14-day-old rats was different from that in 7-to 10-day-old rats, but similar to the adult, in that there was no immunoreactivity in microglia and oligodendrocyte progenitors in subcortical white matter. A proportion of non-pyramidal neurons in cortex were moderately labelled, while some pyramidal neurons were lightly labelled. A population of small glial cells with features of oligodendrocyte progenitors were densely labelled in cortex.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 111 (1996), S. 30-34 
    ISSN: 1432-1106
    Keywords: Dorsal root ganglion cells ; Capsaicin ; Cell diameter ; IH ; Action potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of capsaicin were tested on 221 acutely isolated dorsal root ganglion neurons of the rat, which ranged in diameter from 15 to 55 μm. In a subpopulation of these cells, ranging in diameter from 17.5 to 33 μm (n=117), capsaicin (1 μM) produced an inward shift in holding current that was associated with an increase in membrane conductance in most cells (114 of 117). These effects of capsaicin were reversible upon washout of the drug. Other cells ranging in diameter from 15 to 52.5 μm (n=104) were unaffected in this manner by the 1 μm concentration of capsaicin. Capsaicin-sensitive cells had, on average, significantly longer duration action potentials and expressed significantly less IH than capsaicin-insensitive cells. The relatively long duration action potentials and/or small cell body diameter and paucity of IH observed in most of the capsaicin-sensitive cells is consistent with their representing C- or Aδ-type sensory neurons.
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  • 105
    ISSN: 1432-1106
    Keywords: Buccal stretch receptor ; Development ; Static sensitivity ; Masticatory muscles ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postnatal functional and structural development of the buccal stretch receptor (BSR) of rats was investigated, using electrophysiological and morphological techniques. For functional analysis, sustained discharges in response to ramp-and-hold stretches were recorded from the BSRs isolated from animals aged 10 days to 10 weeks. The threshold amplitude of stretch for a sustained discharge fell significantly between 10 days and 3 weeks, reaching adult values at 5 weeks of age, while the static sensitivity increased conspicuously between 2 and 4 weeks after birth. On the other hand, between 1 and 4 weeks of age, apparent structural changes in the BSR were observed on the number of preterminal branches in a sensory unit, the size of the varicose-like swellings along the terminal axon, the density of collagen and elastic fibers around the core structure, and the content of the sub-capsular space. From these results, we suggest that the increase in the density of the connective tissue around the core structure is associated with an enhancement in the elasticity of the BSR in the early postnatal stages, decreasing the threshold amplitude of stretch for a sustained discharge. One possible explanation for the maturation of the static sensitivity of this receptor is growth of the sensory axon terminals filled with dense mitochondria.
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  • 106
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 111 (1996), S. 371-384 
    ISSN: 1432-1106
    Keywords: Purkinje cell ; Estradiol ; Network ; Performance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuromodulation of Purkinje (Pnj) cell responses by monoamines and estrous hormones is well characterized in the cerebellum at the cellular level, but not at the level of neuronal circuits in the awake behaving animal. In the present study, simultaneous recordings of up to 16 single neurons from within the olivo-cerebellar circuit were obtained through chronically implanted microwire electrode bundles: arrays of Pnj cell like neurons (Pnj cln) in the paravermal cerebellum and neurons within the afferent source of its climbing fiber input, the rostral dorsal accessory olive (rDAO), were recorded simultaneously across 3–20 consecutive estrous cycles during constant or variable speed treadmill locomotion performance tasks. Over 90% of Pnj cln recorded during treadmill locomotion exhibited significant increases (80%) or decreases (10%) in activity correlated with the stance phase of locomotion. In contrast, cells from the rDAO increased activity during speed changes or when the rat failed to maintain the treadmill speed (position slip). On the night of behavioral estrus, which is triggered by elevations in circulating levels of 17β-estradiol and progesterone, the magnitude of both increases and decreases in stance-correlated Pnj cln activity increased by 85–115%. These results are consistent with our previous findings that 17β-estradiol and progesterone enhance excitatory and inhibitory responses of single Pnj cells to locally applied glutamate and GABA, respectively. This dual enhancement of both excitatory and inhibitory effects, apparently paradoxical at the cellular level, produced a marked heightening of the contrast of the neural population “signal” at the neuronal ensemble level. Furthermore, the stance-correlated discharge of Pnj cln during estrus preceded that during diestrus by ∼120ms. Frame-by-frame video analysis also suggested that the swing phase of the step cycle was shortened on estrus compared with diestrus (low hormone state). In addition, rDAO discharge correlated with speed change or position slip was also significantly increased (P〈0.05) on the night of behavioral estrus versus diestrus. Thus, estrus was associated with changes in both the amplitude and the timing of Pnj cln and rDAO discharge correlated with specific behavioral events. These estrous-associated changes in Pnj cell activity were well correlated (r = 0.84) with faster responses to random changes in treadmill speed, a motor performance task. Together, these findings suggest that the increases in the contrast of stancecorrelated Phj cln discharge observed following peak circulating levels of sex steroid hormones are associated with improved motor performance on a randomly moving treadmill.
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  • 107
    ISSN: 1432-1106
    Keywords: Tachykinin receptor ; Retrograde cell labeling ; Optic nerve crush ; Ganglion cell layer ; Inner nuclear layer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Substance P receptor is known to provide a principal interface between tachykinin peptides and tachykinin-sensitive cells in retinal circuitry and to produce several physiological functions such as excitation of ganglion cells. We reported results of in situ hybridization analysis of substance P receptor in rat retina using digoxigenin-labeled RNA probes to yield discrete cell labeling. Distinct hybridization signal was present in a great majority of ganglion cells that provide retinal fibers to a central target. It was also present in a subpopulation of amacrine cells. Following optic nerve crush, ganglion cells lost their hybridization signal in a time-dependent manner, while hybridization-positive amacrine cells were persistently seen. From the results, we identified the hybridization message as distinctly localized to two systems, output cells and intrinsic cells in retinal circuitry.
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  • 108
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 110 (1996), S. 21-27 
    ISSN: 1432-1106
    Keywords: Long-term potentiation ; Auditory cortex ; Pyramidal cell ; NMDA receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In supragranular layers of the rat auditory cortex, white matter stimulation produces antidromic and transsynaptic field potentials, of which only the latter shows long-term potentiation (LTP) following tetanic stimulation of the white matter. In this study, we investigated the cells responsible for the LTP. The transsynaptic field potentials, excitatory postsynaptic potentials (EPSPs), and orthodromic spikes were blocked by 6-cyano-7-nitroquinoxaline-2, 3-dione (10 μM), but not by d-2-amino-5-phosphonovalerate (D-AP5, 50 μM). The latency of EPSPs was constant, while that of transsynaptic field potentials and orthodromic spikes was shortened by the increase in stimulus intensity. Appearance of anti-dromic field potentials and antidromic spikes at strong stimulus intensities were accompanied by reduction in amplitude of transsynaptic field potentials and elimination of orthodromic spikes, respectively. Morphological identification of neurons showing antidromic spikes by intracellular injection of biocytin revealed that most of them were supragranular pyramidal cells. The effects of tetanic stimulation were studied by intracellular recording in seven neurons showing, antidromic spikes, and it was found that only two of them showed LTP of EPSP slope. However, in all of the other eight units showing antidromic spikes and recorded extracellularly, LTP was clearly observed in orthodromic firing probability. The LTP induction in the orthodromic firing probability was blocked by D-AP5. These findings indicate that the LTP in field potentials corresponds to LTP in supragranular pyramidal outputs, and the input-output relationship in neural networks of the adult rat auditory cortex is strongly modulated by LTP.
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  • 109
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 112 (1996), S. 431-441 
    ISSN: 1432-1106
    Keywords: Plasticity ; Auditory cortex ; Neuronal assemblies ; Microstimulation ; Cortical maps ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Single neurons, acting alone, cannot account for the complex and rapid computations that are routinely accomplished by the behaving nervous system. Recent studies with separable multineuron recordings are showing that neuronal assemblies can indeed be detected and that their organization is very dynamic, depending on variables such as time, physical stimulus, and context. Here we explore both single-neuron and assembly properties in the rat's auditory cortex. Acoustic stimuli are used as a normal, physiological input, and weak electrical intracortical microstimulation (ICMS) as a perturbation that forces a rapid cortical reorganization. In this setting, various aspects of neuronal interactions are changed by the ICMS. We found that cortical neurons exhibited highly synchronous oscillatory firing patterns that were enhanced by ICMS. Cross-correlation studies between two spike trains showed that statistically significant correlations depended on the anatomical distance between the two neurons. ICMS changed the strength and the local number of such correlations. Joint petristimulus analysis and gravity analysis showed that the correlation between neuronal activities varied dynamically at several time scales. We have identified neuronal assemblies in two ways, defined through similarity of receptive field properties and defined through correlated firing. Close anatomical spacing between neurons was conducive to, but not sufficient for membership in, the same assembly with either definition. ICMS changed cortical organization by altering assembly membership. Our data show that neuronal assemblies in the rat auditory cortex can be established transiently in time and that their membership is dynamic.
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  • 110
    ISSN: 1432-1106
    Keywords: Infraorbital nerve ; Barrels ; Trigeminal ; Immunocytochemistry ; Peptides ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies in adult animals have suggested that the peptides galanin and neuropeptide Y (NPY) may be upregulated in the same primary afferent neurons after peripheral axotomy. The present study was undertaken to determine whether such upregulation occurred in vibrissae-related primary afferent neurons and their axons after damage to the infraorbital nerve [ION; the trigeminal (V) branch that innervates the vibrissae follicles]. Double-labelling experiments demonstrated that approximately 75% of axotomized V ganglion cells and the central arbors of vibrissae-related primary afferents expressed both galanin and NPY after perinatal, but not adult, nerve damage. However, additional experiments demonstrated that the sensitive periods for lesion-induced upregulation of the two peptides and the period over which they were expressed after neonatal ION transection differed substantially. Staining for both peptides was increased after ION damage on P-0 through P-14, but only galanin staining was increased in vibrissae-related primary afferents after lesions on P-21. Galanin expression was elevated in vibrissae-related primary afferents in rats killed 3,8, and 15 days after neonatal ION transection, while increased NPY was observed at only the middle time point. The lesion-induced increases in galanin and NPY in vibrissae-related ION primary afferents suggest that these peptides may modulate central V reorganization after such damage.
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  • 111
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 108 (1996), S. 285-296 
    ISSN: 1432-1106
    Keywords: Acetylcholine ; Amygdala ; Basal forebrain ; Electrocorticogram ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In urethane-anesthetized rats, electrical 100-Hz stimulation of the basal amygdala changed neocortical electrical activity from 6-Hz or less large-amplitude, irregular slow activity to low-voltage fast activity (LVFA) including frequencies of above 10 Hz. A similar activating effect was seen in the hippocampus, where amygdala stimulation induced the appearance of rhythmical slow activity in the 2 to 6-Hz range. This activation of neocortical and hippocampal activity by amygdala stimulation was blocked by the cholinergic-muscarinic receptor antagonist scopolamine (0.5–5.0 mg/kg i.p.), but not by the peripheral antagonist methylscopolamine, in a concentration-dependent manner. In contrast, a blockade of ascending inputs from the midbrain to the neocortex by treatment with the serotonin-depletor p-chlorophenylalanine or cauterization of the rostral midbrain did not block neocortical LVFA to amygdala stimulation, even though the lesions abolished all LVFA to strong noxious stimuli such as tail pinches. Unilateral infusions of the local anesthetic lidocaine (1%) into the basal forebrain selectively blocked LVFA in the neocortex ipsilateral to the infusion. However, intracerebral or systemic administration of various excitatory amino acid antagonists (2-amino-5-phosphonovaleric acid, kynurenic acid, NPC 12626) was not effective in blocking LVFA to amygdala stimulation. An input from the amygdala to the basal forebrain cholinergic system appears to be one of multiple systems involved in the cholinergic activation of neocortical and hippocampal activity. Further, basal forebrain-cholinergic inputs to the cerebrum alone are sufficient to activate the electrocorticogram, as they sustain activation even in the absence of inputs from the mesencephalon.
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  • 112
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 109 (1996), S. 17-21 
    ISSN: 1432-1106
    Keywords: Circling ; Habenula ; Apomorphine ; Haloperidol ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral circling were not significantly increased when the animals were tested on days 21 and 28, although a contralateral bias was still observed. Rotation induced by apomorphine was completely blocked by the administration of haloperidol (0.3 mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These results indicate that unilateral habenula lesions lead to imbalance of dopaminergic activity, which is expressed as contralateral circling when the animal is challenged with apomorphine.
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  • 113
    ISSN: 1432-1106
    Keywords: Sensory neurons ; Proto-oncogenes ; Corneal pain ; Calcium channel blockers ; Diltiazem ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution and number of trigeminal brainstem and higher order sensory neurons expressing the protein product of the proto-oncogene c-fos after noxious stimulation of the cornea was studied in the rat using immunocytochemistry. The possibility that attenuation of nociceptive messages from the cornea by diltiazem reduced Fos-like immunoreactivity of spinal trigeminal neurons was also examined. A group of animals were killed 2–3 h after corneal stimulation. One cornea was stimulated with: a drop of 10 mM acetic acid; with acid plus mechanical scratching of the corneal epithelium; or with a drop of saline at 56 ° C. Half of the animals treated with acid had been pretreated ipsilaterally with topical diltiazem (10 mM). Control rats received either saline in one eye or no treatment. Another group of animals were killed 7–8 h after stimulation with acetic acid. Fos-like immunoreactive neurons were counted in serial brain-stem sections using an anti-Fos primary antiserum and processed according to the avidin-biotin complex method. In rats killed 2–3 h after corneal stimulation with acid, heat, or acid plus mechanical injury, labelled neurons were found in laminae I and II of the intermediate zone between caudalis and interpolaris subnuclei of the ipsilateral spinal trigeminal nucleus and, in a reduced number, in the symmetrical zones of the contralateral side. In animals stimulated with noxious heat or combined mechanical and chemical injury, a few scattered cells were also labelled in the ipsilateral junction between the cervical spinal cord and the caudalmost part of the trigeminal subnucleus caudalis. In rats killed 7 h after stimulation with acid, stained neurons were observed in the same areas of the trigeminal nucleus as in rats killed at shorter times, but in lower numbers; in these animals, no immunoreactive cells were found in deeper laminae or in higher sensory relay nuclei. Pretreatment with diltiazem significantly reduced the number of cells of the spinal trigeminal nucleus labelled after corneal stimulation with acid. The results indicate that brief noxious stimulation of the cornea evoke expression of c-Fos in neurons of the spinal trigeminal complex. Diminution by diltiazem of the number of immunreactive neurons activated by corneal irritation suggests that this drag, by reducing chemosensitivity of nociceptive terminals, decreases nociceptive inflow to central nervous structures involved in ocular pain perception.
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  • 114
    ISSN: 1432-1106
    Keywords: Urinary bladder ; Inflammation ; Brainstem ; Pontomesencephalic junction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The evoked expression of the immediate early gene encoded proteins c-Fos and Krox-24 was used to study activation of hindbrain neurons as a function of the development of Cyclophosphamide (CP) cystitis in behaving rats. CP-injected animals received a single dose of 100 mg/kg i.p. under transient volatile anesthesia and survived for 1 to 4 h in order to cover the whole postinjection period during which the disease develops. CP-injected groups included: (1) animals with minor simple chorionic edema, an early characteristic of inflammation (1 h postinjection); (2) animals with well developed simple chorionic edema (2 h postinjection); (3) animals with mild inflammation (chorionic edema accompanied by epithelial cleavage; 3 h postinjection); and (4) animals with complete inflammation (4 h postinjection). In addition to onset of chorionic edema, the earliest postinjection period also included the general aspects of the nervous reaction consecutive to the injection process (handling, transient volatile anesthesia and postanesthesia awakening, abdominal pinprick, CP blood circulating effects). Controls included both noninjected animals and saline injected animals surviving for the same times as CP injected ones. Quantitative results come from c-Fos expression. It has been shown that: (1) saline injection is a significant stimulus for only nucleus O and central gray pars alpha and nucleus medialis of the dorsal vagal complex; (2) all structures driven by CP injection (nucleus O and central gray pars alpha, locus coeruleus, Barrington's nucleus and parabrachial area mostly in its ventral and lateral subdivisions, dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) responded vigorously shortly after injection, but only two (dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) showed increased or renewed activity when cystitis completely developed, i.e., when noxious visceral inputs reached highest levels. Regarding the sequential activation of these structures in relation to postinjection time, evidence is given that: (1) a large variety of hindbrain structures are differentially involved in either the general reaction consecutive to the injection process or to various degrees of cystitis; (2) these structures extend from the brain spinal cord to the pons mesencephalon transitional junction levels; (3) the two structures most powerfully driven by visceronociceptive inputs are also the most caudal ones, being located at the brain spinal cord junction level; and (4) the dorsal vagal complex could be the main hindbrain visceral pain center, with three particular subdivisions, the nucleus medialis, nucleus commissuralis, and ventralmost part of area postrema, being involved.
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  • 115
    ISSN: 1432-1106
    Keywords: Calcium ; Hippocampal slice ; CA1 ; ω-Agatoxin IVA ; ω-Conotoxin GVIA ; ω-Conotoxin ; MVIIC ; Nimodipine ; Ethosuximide ; Trimethadion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre-and postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area CA1 of rat hippocampal slices was investigated by measuring the effect of specific blockers on stimulus-induced decreases in extracellular Ca2+ concentration ([Ca2+]0). [Ca2+]0 was measured with ion-selective electrodes in stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and the alveus, respectively. The [Ca2+]0 decreases recorded in SR in response to SR stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]0 decreases recorded in SP in response to alvear stimulation were predominantly based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were ineffective m concentrations up to 1 mM. At 10 mM, they reduced Capost and, much less, also Capre Nimodipine (25 μM) reduced Capost and, to a minor extent, Capre. ω-Agatoxin IVA (0.4–1 μM) and ω-conotoxin MVIIC (1 μM) also reduced both Capre and Capost, but with a stronger action on Capre. ω-Conotoxin GVIA (3–8 μM) reduced Capost without effect on Capre. We conclude that during stimulus-induced, high-frequency neuronal activity Capost is carried by P/Q-, N-, and L-type channels and probably a further channel type different from these channels. Capre includes at least P/Q-and possibly L-type channels. N-type channels did not contribute to Capre in our experiments. Since ethosuximide and trimethadione were only effective in high concentrations, their action may be unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry in this situation.
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  • 116
    ISSN: 1432-1106
    Keywords: Cerebral ischemia ; Magnetic resonance imaging ; Hyperglycemia ; Diffusion imaging ; Reperfusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The early evolution of ischemic brain injury under normoglycemic and streptozotocin-induced hyperglycemic plasma conditions was studied using magnetic resonance imaging (MRI). Male Sprague-Dawley rats were subjected to either permanent middle cerebral artery occlusion (MCAO), or 1-h MCAO followed by reperfusion using the intraluminal suture insertion method. The animals were divided into four groups each with eight rats: normoglycemia with permanent MCAO, normoglycemia with 1-h MCAO, hyperglycemia with permanent MCAO, and hyperglycemia with 1-h MCAO. Diffusion-weighted images (DWIs) and T2-weighted images (T2WIs) were aquired every l h from 20 min until 6 h after MCAO, at which time cerebral plasma volume images (PVIs) were acquired. Tissue infarction was determined by triphenyltetrazolium chloride staining at 7 h after MCAO. The ischemic damage, measured as the area of DWI and T2WI hyperintensity and tissue infarction, increased significantly in hyperglycemic rats in both permanent and transient MCAO models. In the permanent MCAO model, the maximal apparent water diffusion coefficient (ADC) decline under either normoor hyperglycemia was about 40%, but the speed of ADC drop was faster in hyperlgycemic rats than in normoglycemic rats. Reperfusion after l h of MCAO in normoglycemic rats partly reversed the decline in ADC, whereas the low ADC area continued to expand after reperfusion in the hyperlgycemic group. Between the two hyperglycemic groups with either permanent MCAO or reperfusion, no significant difference was found in the infarct volume measured at 7 h after MCAO. However, reperfusion dramatically increased the extent and accelerated the development rate of vasogenic edema. ADC in the hyperglycemic reperfusion group also dropped to a lower level. A large “no-reflow” zone was found in the ischemic hemisphere in the hyperglycemic reperfusion group. This study provides strong evidence to support that preischemic hyperglycemia exacerbates ischemic damage in both transient and permanent MCAO models and demonstrates, using MRI, that reperfusion under preischemic hyperglycemia accelerates the evolution of early ischemic injury.
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  • 117
    ISSN: 1432-1106
    Keywords: Differential-pulse voltammetry ; Dopamine ; Caudate putamen ; Neural grafting ; Non-grafted side ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study employed differential-pulse voltammetry to assess the influence of foetal ventral mesencephalic grafts on dopamine overflow in the contralateral caudate putamen of the 6-hydroxydopamine rat model of Parkinson's disease. The experimental design involved measurements of dopamine overflow in the grafted and contralateral striatum. Control measurements of dopamine overflow were performed in 6-hydroxydopamine-lesioned rats only and the caudate putamen of normal control rats. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted into the dopamine-depleted caudate putamen of unilaterally 6-hydroxydopamine-lesioned rats. At 6 weeks, animals with functional, mature grafts (as assessed by amphetamine-amplified behavioural asymmetry), were pretreated with pargyline (75 mg/kg i.p.), and both striatal sides were monitored for dopamine overflow for 90 min following amphetamine sulphate administration (5 mg/kg i.p.). The time course of dopamine overflow inside the graft was similar to that in the contralateral caudate putamen of the same animal, the normal control animal and the contralateral caudate putamen of 6-hydroxydopamine-lesioned animals. However, in grafted animals the mean dopamine overflow detected in the contralateral caudate putamen was approximately 34% lower than the concentration of dopamine detected in the contralateral caudate putamen of 6-hydroxydopamine-lesioned control animals and approximately 39% lower than the concentration of dopamine detected in the caudate putamen of the normal control animal. There was no statistical difference in the concentration of amphetamine-induced dopamine overflow between the caudate putamen contralateral to the 6-hydroxydopamine lesion and the caudate putamen of the normal control animal. These data suggest that intrastriatal foetal ventral mesencephalic suspension grafts reduce amphetamine-induced dopamine release in the contralateral non-grafted caudate putamen.
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  • 118
    ISSN: 1432-1106
    Keywords: Trigeminal nerve ; Primary afferents ; Synapses ; Ultrastructure ; Vibrissae ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonatal transection of the infraorbital nerve (ION; the trigeminal, V, branch that supplies the mystacial vibrissae follicles) results in an upregulation of galanin in the central arbors of primary afferent axons. The present study was undertaken to evaluate the synaptic organization of these galanin-positive primary afferents and compare it with that of normal neurobiotin/biocytin-labeled primary afferent axons from animals of the same age. Examination of 1200 neurobiotin/biocytin-labeled profiles in V nucleus principalis (PrV) of rats killed on postnatal day (P-) 7 indicated that 23.3% (n=279) of these profiles made synaptic contacts: 87.4% were axodendritic, 8.9% were axoaxonic, 2.8% were axosomatic, and 0.7% were axospinous. Evaluation of 1200 galanin-positive profiles in PrV from rats that sustained transection of the ION on P-0 and were killed on P-7 indicated that only 64 (5.3%) of these profiles made synaptic contacts (P〈0.05 compared with the intact animals). Of the galanin-positive profiles that did make synapses in PrV, 81.2% (n=52) were axodendritic and 18.8% (n=12) were axoaxonic. These results indicate that galanin released by damaged ION primary afferents in PrV is likely to affect the activity of second-order V neurons by a paracrine action rather than by acting at specific synapses.
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  • 119
    ISSN: 1432-1106
    Keywords: Calcium current ; Cerebellar granule neuron ; Heloderma ; Helodermine ; Ion channel block ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Helothermine (HLTx), a 25.5-kDa peptide toxin isolated from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to be an inhibitor of Ca2+ channels in cerebellar granule cells of newborn rats. Macroscopic currents, carried by 10 mM Ba2+, were measured in whole-cell configuration. The toxin at the saturating dose of 2.5 μM reversibly produced an ≈67% block of the voltage-dependent Ca2+ current by a fast mechanism of action. The current inhibition and recovery were reached in less than 1 min. Inhibition was concentration-dependent, with a half-effective dose of 0.25 μM. The current block was practically voltage-independent, whereas the steady-state inactivation h ∞ was significantly affected by HLTx (≈10 mV). The toxin did not affect the activation and inactivation kinetics of the Ca2+ current. Experiments with other Ca2+ channel blockers showed that HLTx abolished ω-conotoxin GVIA-sensitive Ca2+ currents, as well as ω-AgaIVA- and dihydropyridine-sensitive Ca2+ currents. These drugs had virtually no effect when HLTx was applied first. The present results indicate that HLTx produce a high-potency blockage of the three pharmacologically distinct Ca2+ current components.
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  • 120
    ISSN: 1432-1106
    Keywords: Intracortical microstimulation ; c-fos ; Ca2+/calmodulin-dependent protein kinase II ; Glutamic acid decarboxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-train tetanic stimulation of the cerebral cortex induces long-term changes in the excitability of cortical neurons, while short-train electrical stimulation does not. In the present study, we show that both forms of stimulation when applied to rat motor cortex for 4 h enhance c-fos expression, but only tetanic stimulation, when imposed upon short-train stimulation, modulates gene expression for 67-kDa glutamic acid decarboxylase (GAD) and alpha Ca2+/calmodulin-dependent protein kinase II (CaMKIIα). Gene expression for beta Ca2+/calmodulin-dependent protein kinase II is not affected by either stimulation mode. GAD messenger RNA (mRNA) is increased from 1 h after the end of tetanization to the longest poststimulus survival time investigated (14 h). CaMKIIα mRNA is decreased 1–3 h after the end of tetanization but thereafter returns to prestimulus levels. These results imply not only that mechanisms underlying neocortical plasticity are stimulus-dependent but also that they involve reciprocal changes in molecules regulating the balance of excitation and inhibition.
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  • 121
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Parkinson's disease ; Tissue cultures ; Mesencephalon ; Human embryo ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Free-floating roller tube cultures of human fetal (embryonic age 6–10 weeks post-conception) and rat fetal (embryonic day 13) ventral mesencephalon were prepared. After 7–15 days in vitro, the mesencephalic tissue cultures were transplanted into the striatum of adult rats that had received unilateral injections of 6-hydroxydopamine into the nigrostriatal bundle 3–5 weeks prior to transplantation. Graft survival was assessed in tyrosine hydroxylase (TH)-immunostained serial sections of the grafted brains up to post-transplantation week 4 for the human fetal xenografts and post-transplantation week 11 for the rat fetal allografts. d-amphetamine-induced rotation was monitored up to 10 weeks after transplantation in the allografted animals and compared with that of lesioned-only control animals. All transplanted animals showed large, viable grafts containing TH-immunoreactive (ir) neurons. The density of TH-ir neurons in the human fetal xenografts and in rat fetal allografts was similar. A significant amelioration of the amphetamine-induced rotation was observed in the animals that received cultured tissue allografts. These results promote the feasibility of in vitro maintenance of fetal human and rat nigral tissue prior to transplantation using the free-floating roller tube technique.
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  • 122
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    Experimental brain research 110 (1996), S. 347-359 
    ISSN: 1432-1106
    Keywords: Glutamate ; Aspartate ; Developing neocortex ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The excitatory amino acids l-glutamate and l-aspartate are believed to be utilized as neurotransmitters by the pyramidal neurons in the mammalian cerebral cortex. These cells can be recognized early in development, while glutamate might play an important part in the maturation and plasticity of the cortex. Here, we used light and electron microscopic immunocytochemistry to study the time of appearance and maturation of glutamate and aspartate in neurons of the rat visual cortex. Glutamate- and aspartate-immunoreactive cells were first detected in deep cortical layers at postnatal day 3. During the next 3 weeks, labelled neurons were observed progressively in more superficial layers, but did not demonstrate their adult pattern of distribution until postnatal week 4. Electron microscopic analysis showed that glutamate- and aspartate-labelled neurons gradually develop their cytological and synaptic features during the first 4 postnatal weeks, with this process of differentiation originating in the deep cortical layers and progressively extending to the superficial layers. These findings suggest that cortical pyramidal neurons begin to express detectable levels of transmitter glutamate and/or aspartate after they have completed their migration. Their neurochemical differentiation follows an “inside-out” pattern similar to the pattern described for the genesis and morphological differentiation of this population of cortical neurons.
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  • 123
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Turning ; Cerebellum ; Substantia nigra ; Basal ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a recent electrophysiological experiment, we showed the deep cerebellar nuclei to be a major source of excitatory input to the superior colliculus. Furthermore, target neurons in the colliculus were found, in every case, to receive convergent tonic inhibitory input from the substantia nigra pars reticulata. In the present study, we investigated these effects in the awake rat. We asked whether circling behaviour, induced by unilateral injection of a GABA antagonist into the lateral colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were chronically implanted with bilateral guide cannulae located above the superior colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was microinjected unilaterally into intermediate layers of the colliculus at increasing depths until an optimal contralateral circling response was elicited. This behaviour was taken as the “baseline response” and was the first of three treatments. The second was an identical manipulation of the colliculus with a concurrent 200-nl microinjection of 1 M GABA into the contralateral deep cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if rotation had been suppressed by more than 50% on test 2, the treatment was collicular BIC plus deep cerebellar saline. This latter treatment was used as a control for possible non-pharmacological injection effects. The effect of cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC-induced rotation at 15 collicular sites was studied in ten animals. Only GABA injections at sites that fell within the cerebellar nuclei significantly reduced turning (P〈0.0001). A full behavioural analysis showed that this was a specific suppression of turning, not the result of general motor impairment. These results provide clear behavioural evidence that opposing, convergent influences from the basal ganglia and cerebellum interact in the lateral superior colliculus to control head and body movements. They furthermore suggest that the tonic deep cerebellar excitation of the superior colliculus could be the driving force in the expression of rotation induced by manipulations of the basal ganglia.
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  • 124
    ISSN: 1432-1106
    Keywords: Cell death ; Neurotrophins ; Retrograde labeling ; Tyrosine hydroxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraparenchymal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle in rats destroys the dopaminergic neurons in the pars compacta of the substantia nigra. In other transmitter systems it has been found that axotomy or neurotoxin exposure produces an initial loss of neurotransmitter phenotype, with cell death occurring over a much slower time course. To determine whether this also occurs in dopamine neurons after 6-OHDA, two approaches were utilized. First, the effect of injections of 6-OHDA into the medial forebrain bundle on nigral dopaminergic neurons was studied using combined fluorogold and immunocytochemical labeling. Four weeks after the 6-OHDA injection, there was an 85% reduction in the number of tyrosine hydroxylase (TH)-immunoreactive cells on the lesioned side. In contrast, there was only a 50% reduction in the number of fluorogold-labeled cells on the lesioned side. Second, the time course of the rescue of dopaminergic neurons after 6-OHDA by glial cell line-derived neurotrophic factor (GDNF) was determined using TH immunocytochemistry. Greater numbers of dopamine neurons were rescued 9 weeks after GDNF, compared with counts made 5 weeks after GDNF. Taken together, these results suggest loss of dopaminergic phenotype is greater than cell loss following 6-OHDA injections, and that GDNF restores the phenotype of affected cells.
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  • 125
    ISSN: 1432-1106
    Keywords: Male sexual behavior ; Vasopressin ; Limbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During sexual behavior in the male rat, peptidergic cells in the medial amygdaloid nucleus become active and release a vasopressin-like peptide. The present experiments were designed to examine hippocampal changes as a result of this peptide's action during sexual behaviors. Chronic field-potential recordings from the hippocampus of male rats were acquired in a wide variety of social and nonsocial circumstances. Hippocampal responses that resemble the known action of the vasopressin-like peptide were seen only with social stimuli such as sexual stimuli and stimuli that led to aggressive behavior between males. The results show that the occasions of peptide action in the hippocampus correlate with the occasions of peptide release as determined by recording from the peptidergic cell bodies. The results are interpreted to indicate that the amygdala projection to the hippocampus has a special role to play in social behavior.
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  • 126
    ISSN: 1432-1106
    Keywords: Retrorubral field ; Hippocampal formation ; Mesolimbic dopaminergic system ; Phaseolus vulgaris leucoagglutinin ; Tyrosine hydroxylase immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dopaminergic neurons in the midbrain of the rat are located in three groups: the ventral tegmental area (VTA-A10), substantia nigra (SN-A9), and retrorubral field (RRF-A8). We have recently examined the organization of the projections from the VTA and the SN to the hippocampal formation (HF) in the rat. In the present study we characterize the projections of the RRF to the HF by using anterograde tracing, retrograde tracers, and tyrosine hydroxylase (TH) immunohistochemistry. Following iontophoretical injections of Phaseolous vulgaris leucoagglutinin (PHA-L) into the RRF, anterograde labeling was observed primarily in the ipsilateral subiculum and adjacent CA1 cell field. Sparse labeling was also observed in the CA3 cell field and dentate gyrus. The distribution of RRF neurons projecting to the HF was examined by injecting retrograde fluorescent tracers (fluorogold, fast blue, and nuclear yellow) into several hippocampal areas. The retrograde tracer findings indicate that the medial aspects of the RRF project to the subiculum and adjacent CA1 cell field of both the septal and temporal HF. In order to evaluate the percentage of dopaminergic cells of the RRF projecting to the HF, the retrograde neuronal tracer fluorogold was used in combination with TH immunohistochemistry. The quantitative evaluation of retrograde labeled and TH-immunoreactive (IR) cells showed that RRF projections to the HF are partially (10–18%) dopaminergic. The findings suggest that the general pattern of distribution and organization of the RRF-A8 projections to the HF is similar to that observed in our previous studies examining hippocampal afferents from the VTA and SN. The data also suggest a crude topographical organization of RRF afferents to the HF and a more prominent input to the temporal than to the septal HF.
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  • 127
    ISSN: 1432-1106
    Keywords: Perinatal asphyxia ; Dopamine utilization ; Tyrosine hydroxylase activity ; Substantia nigra ; Neostriatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was undertaken in order to study the effects of perinatal asphyxia on tyrosine hydroxylase (TH) activity, dopamine levels and turnover, and dopamine metabolites (3,4-dihydroxyphenylacetic acid, DOPAC, homovanillic acid, HVA, and 3-methoxytyramine, 3-MT, analyzed by high-performance liquid chromatography, HPLC) measured in the basal ganglia of the 20- to 40-min-old newborn and 4-week-old male rat. Asphyxia was induced in pups by placing the fetuses, still in their uterus horns removed by hysterectomy from pregnant rats at full term, in a 37°C water bath for 15–16 min or 19–20 min. Following asphyxia, the uterus horns were opened, and the pups were removed and stimulated to breathe. A 100% and 50–80% pup survival was obtained following 15–16 min and 19–20 min of asphyxia, respectively. Acute changes were studied in brains from newborn pups 20–40 min after delivery, and long-term changes were studied in brains from 4-week-old rats. No changes in TH-activity could be observed in the substantia nigra/ventral tegmental area (SN/VTA), the striatum, or the accumbens nucleus/olfactory tubercle (ACC/TUB), in the newborn or the 4-week-old rat. In the newborn rat, 19–20 min of asphyxia increased (as compared to controls) dopamine levels in the SN/VTA to 136±14% and in the ACC/TUB to 160±10%, indicating an increased synthesis and/or release of dopamine. DOPAC levels were increased in the SN/VTA to 150±14% and in the ACC/TUB to 151±10%, and HVA levels were increased to 152±16% in the striatum and to 117±4% in the ACC/TUB. Following 15–16 min of asphyxia, dopamine levels were increased to 130±12% in the ACC/TUB, and DOPAC levels were increased to 135±6% and 130±12% in the SN/VTA and the ACC/TUB, respectively. This suggests that the increased dopamine levels may preferably reflect an increased release of dopamine following perinatal asphyxia. In the 4-week-old rat, dopamine levels were decreased in the SN/VTA to 71±4%, in the striatum to 52±8%, and in the ACC/TUB to 53±7%, following 19–20 min of perinatal asphyxia as compared to controls. No changes were observed in DOPAC, HVA, or 3-MT levels, indicating that the reduced dopamine levels reflect a reduced dopamine synthesis following perinatal asphyxia. A decrease in dopamine utilization was observed in the striatum to 15±8% and in the ACC/TUB to 9±13% following 19–20 min of perinatal asphyxia as compared to controls. This indicates that perinatal asphyxia produced long-lasting reductions in activity in the mesostriatal/mesolimbic dopamine systems in the 4-week-old rat.
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  • 128
    ISSN: 1432-0738
    Keywords: Key words L-2-Chloropropionic acid ; Glutathione ; Cerebellar granule cell necrosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The role of glutathione (GSH) in the neurotoxicity produced following a single oral dose of 750 mg/kg L-2-chloropropionic acid (L-CPA) has been investigated in rats. L-CPA-induced neurotoxicity was characterised by up to 80–90% loss in cerebellar granule cells and cerebellar oedema leading to locomotor dysfunction. Neurochemically, L-CPA-induced neurotoxicity produced a reduction in the concentration of aspartate and glutamate in the cerebellum and a reduction in the density of NMDA receptors in the cerebellar cortex, whilst there was an increase in cerebellar glycine, glutamine and GABA concentrations. Treatment of rats with buthionine sulfoximine (BSO) at 1 g/kg, i.p., an inhibitor of GSH synthesis, potentiated the toxicity of L-CPA, such that many of the neurochemical markers were significantly different from controls at earlier time points, compared to animals which had received L-CPA alone, and toxicity was also seen in the kidney of BSO plus L-CPA treated rats. In contrast, supplementing GSH concentrations by administration of the isopropyl ester of glutathione (ip-GSH) at 1 g/kg, s.c., was able to protect rats against L-CPA neurotoxicity and prevent many of the neurochemical changes. In order to assess whether the depletion of GSH in the rat cerebellum following L-CPA treatment was related to the delivery of cysteine or cystine, the accumulation of [14C] cystine into cerebellar slices was characterised and found to be energy dependent, Na+ independent and obey saturation kinetics with an apparent Km of 77 μM and an apparent Vmax of 450 nmol/g wet weight per h. The accumulation of cystine into cerebellar slices was non-competitively inhibited by the cysteine conjugate of L-CPA with an apparent Ki of approximately 60 μM, whilst glutamate only inhibited cystine accumulation at doses which were cytotoxic to cerebellar slices. Hence the depletion of GSH in the rat cerebellum, following L-CPA administration, may be due to a reduction in the delivery to the brain of cysteine or cystine, one of the components required for GSH synthesis, by the cysteine conjugate of L-CPA. Our studies show the pivotal role GSH plays in cerebellar granule cell necrosis induced by L-CPA in the rat, indicating that a marked and sustained reduction in cerebellar GSH content by L-CPA may leave granule cells vulnerable to cytotoxic free radical damage leading to cell death, possibly mediated through excitatory amino acids.
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  • 129
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    Archives of toxicology 70 (1996), S. 474-481 
    ISSN: 1432-0738
    Keywords: Key words Quinolone (♪) ; Cartilage lesions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The reversibility of quinolone-induced cartilage lesions has not been studied in detail. We treated five groups of five to seven juvenile Wistar rats (male and female; age: 5 weeks) with 2×600 mg ofloxacin/kg by gastric intubation on 1 day only (9:00 a.m. and 5:00 p.m.) and studied the knee joints histologically 3 days, 1, 3, 8 and 17 weeks later. In addition, joint cartilage specimens from vehicle-treated control rats (n=21) at corresponding age were examined. Cartilage lesions such as matrix swelling, loss of proteoglycans and horizontal clefts were found in nearly all knee joints (26 of 27 joints; incidence: 96%) of the ofloxacin-treated rats. Within the observation period of 4 months the size of these lesions in knee joint cartilage did not decrease significantly. The diameter of the lesions at the time points of evaluation was 1146±535, 1713±309, 1250 ±585, 1406±356, and 1542±467 μm, respectively (mean values±sd). Chondrocyte clusters producing glycosaminoglycans were observed 3 weeks after dosing and at later time points. They are considered to reflect the onset of repair but chondrocyte organization did not normalize during the study period, thus indicating the irreversibility of the effect under the experimental conditions. In principle, long-term joint cartilage damage has to be taken into account when the use of quinolones in children is considered. More detailed pharmacokinetic data are necessary for a reasonable risk assessment approach.
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  • 130
    ISSN: 1432-0738
    Keywords: Key words Cadmium ; Erythropoietin ; Anemia ; Rat ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells.
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  • 131
    ISSN: 1432-0738
    Keywords: Key words Hexachlorobenzene ; Rat ; Operant behavior ; Gestation ; Liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hexachlorobenzene (HCB) is still frequently found at elevated levels in human adipose tissue and breast milk. As intoxication with HCB causes neurological disturbance in human beings, the purpose of the present study was to examine neurobehavioral functions in rats after pre- and postnatal exposure. Female rats were fed diets with 0, 4, 8, or 16 mg HCB/kg diet. Exposure started 90 days prior to mating and was continued throughout mating, gestation, and lactation. Thereafter, the offspring were given the same diets as their respective mothers. HCB levels were determined in the brain, the liver, and in the adipose tissue from virgin rats, dams, and the offspring. Concentrations on a lipid basis were found to decline in the order adipose〉liver〉brain. The exposure levels chosen did not cause gross toxic effects in dams or offspring. There were dose-related increases in liver-to-body-weight ratios in exposed dams, but not in unmated females treated alike. Behavioral testing was conducted in the offspring. Examination of open-field activity on PND 21, and of active avoidance learning on PND 90 failed to reveal significant differences between groups. Training of operant behavior started at the age of 150 days in the offspring from the control, the 8-mg group, and the 16-mg group. Animals were trained on a fixed interval schedule of 1 min (FI-1). On this schedule, responses were reinforced by a food pellet every time 1 min had elapsed after the preceding reinforcement. There were dose-dependent reductions in the post-reinforcement pause, e.g. the time between each reinforcement and the first reaction emitted after it. In addition, the index of curvature, which describes the efficiency of performance on the FI-1 schedule, was decreased in a dose-dependent fashion.
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  • 132
    ISSN: 1432-0738
    Keywords: Key words Glutathione ; Glutathione-related enzymes ; Hepatocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of culture medium on glutathione (GSH) dependent detoxification defence system of primary cultured hepatocyte from either male or female rats was studied. Intracellular reduced (GSH) and oxidized glutathione (GSSG), and six GSH-related enzyme activities, including GSH peroxidase (GSH Px), GSH reductase (GSH Rd), cytosolic GSH S-transferase (cGST), microsomal GSH S-transferase (mGST), γ-glutamyl transpeptidase (GTP), and γ-glutamylcysteine synthetase (GCS), were investigated during a 6-day culture. Media free of fetal bovine serum (FBS) and with 2.5 or 10% FBS were used. Whatever the medium, there was an initial increase of intracellular GSH and GSSG, a threefold increase of GSH at day 3 and fourfold increase of GSSG at day 4, later decreasing to their original level at day 6. The activities of all six GSH-related enzymes of male and female hepatocytes remained relatively stable during the first 72 h, then gradually decreased to 50–80% of initial activities. With the exception of cGST, time-course profiles of other enzyme activities were not significantly different among various media. In both sexes, higher cGST activity was maintained for cells cultured in the presence of FBS. Results of immunoblotting analysis of cytosolic GST isozymes indicate that the placental form of GST (Yp) was markedly increased after plating and the extent of increase of Yp was higher in the presence of FBS. Despite the culture medium, the level of GST isoform Ya was maintained steadily for 6 days, however, Yb was maintained during the first 3 days and then decreased. In terms of the gender difference, GSH Px and GTP activities of hepatocytes from females were significantly greater than of males over the entire culture period. Results indicate that FBS seems not to be absolutely essential in maintaining GSH level and most of the GSH-related enzyme activities in rat hepatocytes. Furthermore, GSH levels and GSH-related enzyme activities of hepatocytes from female rats were similar to those from male rats.
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  • 133
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    Archives of toxicology 70 (1996), S. 310-314 
    ISSN: 1432-0738
    Keywords: Key words Methylmercury ; Mercury ; Placenta ; Neutral amino acid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Methylmercury (MeHg) penetrates the placental barrier to affect developing fetuses in the uterus. However, the mechanism of placental MeHg transport is not well defined. To clarify the MeHg transport system that functions in the placenta, pregnant rats were intravenously administered MeHg on day 18 of gestation. The fetal blood was collected from the umbilical cord at 30 and 60 min after the administration, and its mercury concentration was measured. MeHg was found to be rapidly transported to the fetal blood in a time- and dose-dependent manner, and predominantly distributed in the blood cells there. MeHg transport was effectively suppressed by the co-injection of neutral amino acids, i.e., L-methionine and L-phenylalanine, suggesting that MeHg is actively transported as its cysteine conjugate via the neutral amino acid carrier system. The suppression by methionine was not so marked as by phenylalanine. Since methionine administration caused a rapid increase of the cysteine, which functioned as a predominant carrier in MeHg transport, in the maternal plasma, newly synthesized cysteine seemed to accelerate the mercury uptake. Accordingly, the acceleration by the extra cysteine would compensate partly the competitive effect of methionine as a neutral amino acid.
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  • 134
    ISSN: 1432-0738
    Keywords: Key words Formaldehyde ; Acrolein ; Acetaldehyde ; Rat ; Sensory irritation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the mixtures were chosen in such a way that summation of the effects of each chemical would be expected not to exceed 80% reduction of the breathing frequency. FRM, ACR and ACE appeared to act as sensory irritants as defined by Alarie (1966, 1973). With FRM and ACR desensitization occurred, whereas with ACE the breathing frequency gradually decreased with increasing exposure time (up to 30 min). For mixtures, the observed DBF was more pronounced than the DBF for each compound separately, but was less than the sum of the DBFs for the single compounds. A model for three compounds competing for the same receptor was applied to predict the DBF of mixtures of FRM, ACE and ACR. The results also showed that with mixtures no desensitization occurred; in fact, the breathing frequency further decreased in the last 15 min of exposure. These observations were similar to those found for ACE alone, and might have been caused by effects on the upper respiratory tract. The results of the present study allow the conclusion that sensory irritation in rats exposed to mixtures of irritant aldehydes is more pronounced than that caused by each of the aldehydes separately, and that the DBF as a result of exposure to a mixture could well be predicted using a model for competitive agonism, thus providing evidence that the combined effect of these aldehydes is basically a result of competition for a common receptor (trigeminal nerve).
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  • 135
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    Archives of toxicology 70 (1996), S. 368-372 
    ISSN: 1432-0738
    Keywords: Key words Phenobarbital ; 2-Aminoisobutyric acid ; Hepatoytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Phenobarbital (PB) is a classical inducer of drug metabolizing enzymes and known to stimulate liver growth transiently in rodents. Previous studies have shown that regenerative liver growth after a partial hepatectomy is accompanied by the induction of the amino acid transport system A. In the present study we investigated whether amino acid transport is also increased by treatment of rats with PB. Na+-dependent hepatic uptake of the non-metabolizable amino acid 2-aminoisobutyric acid (AIB), which proceeds largely via transport system A, was studied in isolated hepatocytes from PB treated and untreated rats. Uptake of AIB (100 μM) was maximally induced (2.5-fold) 8 h after the beginning of PB treatment. Within 4 days, transport rates decreased to values similar to those determined in hepatocytes from untreated animals, despite the continuation of PB treatment. In contrast, induction of the PB-inducible cytochromes P450 2B1/2 was markedly increased during the entire experiment, as determined with the isoenzyme-selective substrate pentoxyresorufin. Kinetic analysis of AIB uptake revealed a “high” and a “low” affinity transport system. It is most likely that the high affinity system represents amino acid transport system A. Treatment with PB increased the Vmax value but did not affect the apparent Km value of the high affinity system. The present data suggest that the hepatic mitogen PB transiently induces amino acid transport system A.
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  • 136
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    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    ISSN: 1432-2218
    Keywords: Laparoscopy ; Rat ; Tumor take ; Weight loss ; Pneumoperitoneum ; Bowel resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
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  • 137
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    Psychopharmacology 123 (1996), S. 98-102 
    ISSN: 1432-2072
    Keywords: Sucrose ; Raclopride ; 5-HT2 antagonism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effects on sucrose consumption of a dopamine (DA) D2/D3 antagonist (raclopride, 0–0.3 mg/kg), a serotonin 5-HT2/2c antagonist (ritanserin, 0–0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin (0–0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and 34%) were tested. The concentration-intake function in drug-free rats was an inverted-U, with 7.0% sucrose supporting the highest intake. Raclopride (0.3 mg/kg) inhibited intake of 7.0% sucrose, but its effect on 0.7% sucrose fell short of significance (P〈0.06) and intake of 34% sucrose was unchanged. Ritanserin did not affect sucrose intake when given on its own, but synergized with a previously ineffective dose of raclopride (0.15 mg/kg) so as to cause a significant inhibition of 7.0% sucrose intake and increase in 34% sucrose intake. These data indicate that 5-HT2 antagonism potentiated the behavioural effects of raclopride and we speculate that this interaction might contribute to the efficacy of atypical neuroleptic drugs.
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  • 138
    ISSN: 1432-2072
    Keywords: 2,4-Dithiobiuret ; Rat ; Cognitive facilitation ; Motor impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg per day IP for 5 days) was used to induce motor dysfunction as a way to dissociate peripheral and central influences on a test of cognitive and motor function in rats. Sixteen male rats were trained to perform a Delayed Matching-to-Position/Visual Discrimination (DMTP/VD) task which permits quantification of working memory (matching accuracy), reference memory (discrimination accuracy), and motor function (choice response latency and nosepoke inter-response time, IRT). The first dose of DTB significantly increased matching accuracy; during the following week, DTB reduced matching accuracy, increased choice response latency and nosepoke IRT, and reduced trial completion. Discrimination accuracy remained unaffected. Experiment 2 explored the effects of single administrations of DTB on DMTP/VD. Sixteen other trained rats were divided into two groups with equal matching accuracy. One group received DTB (0.5,1.0, and 2.0 mg/kg, IP) in separate injections at least 1 week apart; the other group received vehicle at the same times. Matching accuracy increased significantly in the treated rats and not in the controls following each dose of DTB. The magnitude of this increase was dose-dependent, and lasted from 1 to 8 weeks after each injection. Discrimination accuracy, response latency, nosepoke IRT and trial completion remained unaffected throughout the study. After DTB, matching accuracy was less easily disrupted by scopolamine (0.1–0.3 mg/kg, IP). However, DTB did not alter the rats' response to reducing the distance between the response levers, to reversal of the matching rule to a nonmatching rule, or to challenge with MK-801 (0.05–0.10 mg/kg, IP). These data indicate that acute DTB causes a long-lasting facilitation of working memory in rats in the absence of any of the indications of motor impairment which follow repeated, daily injections of the chemical.
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  • 139
    ISSN: 1432-2072
    Keywords: Key words Thyrotrophin-releasing hormone ; RX77368 ; Alzheimer’s disease ; AMPA ; Septal-hippocampal ; Working memory ; Delayed non-matching to position (DNMTP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a post-surgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg–1, IP) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8–10 and 11–13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.
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  • 140
    ISSN: 1432-2072
    Keywords: Key words Opioids ; Tolerance ; Neurotensin ; NMDA ; Conditioning ; MK-801 ; Morphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Opiate tolerance involves both associative and non-associative changes. However, procedures designed to distinguish between these two processes have rarely been employed when investigating the physiological basis of such plasticity. The present experiments assessed some of the mechanisms contributing to both associative and non-associative decreases in morphine analgesic potency following repeated IV morphine administration (4 days, 5 mg/kg per day). For one group of rats, testing for morphine analgesia (tailflick) occurred in a context that had been repeatedly paired with morphine administration. Another group of rats, exposed equally to the testing context, handling procedures and morphine, was tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the unpaired group. We evaluated the spinal cord involvement of NMDA receptors, as well as the peptide neurotensin in these two types of tolerance. NMDA receptors appeared to mediate non-associative changes in drug potency, as rats tested in either context were less tolerant when morphine administration was preceded with the non-competitive NMDA antagonist, MK-801 (2.5 and 5 nmol). Spinal neurotensin antagonism with [d-Trp11]neurotensin (3 pmol) selectively abolished associative tolerance. These findings provide information about the mechanisms of opiate tolerance and support the distinction between associative and non-associative processes underlying these changes.
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  • 141
    ISSN: 1432-2072
    Keywords: Alzheimers' disease ; α2-Adrenoceptor antagonists ; Acetylcholinesterase inhibitor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cholinergic hypothesis of Alzheimer's disease (AD) has strongly influenced research on learning and memory over the last decade. However, there has been limited success treating AD dementia with cholinomimetics. Furthermore, there are indications that other neurotransmitter systems affected by this disease may be involved in cognitive processes. Animal studies have suggested that norepinephrine and acetylcholine may interact in learning and memory. The current experiments investigate this interaction in a step-down passive avoidance paradigm after coadministration of acetylcholinesterase inhibitors and α2-adrenoceptor antagonists. Administration of acetylcholinesterase inhibitors heptylphysostigmine (0.625–5.0 mg/kg, IP), tacrine (2.5–10.0 mg/kg, PO), velnacrine (0.312–2.5 mg/kg, SC), and galanthamine (0.312–2.5 mg/kg, IP) each enhanced retention of a passive avoidance response at selected moderate doses administered 30–60 min prior to training. The α2-adrenoceptor antagonists idazoxan (0.312–2.5 mg/kg, IP), yohimbine (0.078–0.312 mg/kg, IP) and P86 7480 (0.156–0.625 mg/kg, IP) alone failed to enhance learning in this paradigm. Coadministration of a subthreshold dose of heptylphysostigmine (0.625 mg/kg, IP) with doses of idazoxan, yohimbine or P86 7480 enhanced passive avoidance learning. This synergistic interaction may represent effects of antagonism of presynaptic α2-adrenoceptor since coadministration of heptylphysostigmine and the selective postsynaptic α2-adrenoceptor antagonist SKF104856 did not result in enhanced learning. Taken together these data suggest noradrenergic activation through pre-synaptic α2-adrenoceptor blockade may potentiate cholinergic activity in the formation of a long-term memory trace. These observations may have implications for the treatment of AD with cholinergic and adrenergic agents.
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  • 142
    ISSN: 1432-2072
    Keywords: Social recognition ; Memory ; Rat ; Mouse ; Cannabimimetic ; Cannabinoid antagonist ; SR 141716 ; Ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.
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  • 143
    ISSN: 1432-2072
    Keywords: SKF 38393 ; Quinpirole ; SCH 23390 ; l-Sulpiride ; Nucleus accumbens shell ; Nucleus accumbens core ; Turning behaviour ; Dopamine D1 and D2 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The goal of this study was to determine whether dopamine D2 and/or D1 receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral injection of a mixture of the dopamine D2 receptor agonist quinpirole (10 µg) and the dopamine D1 receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 µg) into the shell of the nucleus accumbens produced contralateral turning, when doses which per se were ineffective were injected. This effect was far greater than that found after similar injections into the core of the nucleus accumbens. The effect elicited from the shell was significantly attenuated by prior administration of either the dopamine D2 receptor antagonistl-sulpiride (25 ng/0.5 µl) or the dopamine D1 receptor antagonist (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 µg/0.5 µl) into the same region. These data together with the fact thatl-sulpiride is known to be a valid tool to differentiate the involvement of distinct regions within the shell underlie the conclusion that dopamine D2 and D1 receptors in the shell, but not the core, of the nucleus accumbens play a critical role in the contralateral turning induced by unilateral injection of dopamine receptor agonists into this nucleus. The results are discussed in view of the known output pathways of the shell.
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  • 144
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    Psychopharmacology 126 (1996), S. 286-292 
    ISSN: 1432-2072
    Keywords: Modafinil ; Ephedrine ; Cocaine ; Amphetamine ; Self-administration ; Drug discrimination ; Rhesus monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant drug which is effective in the treatment of narcolepsy and idiopathic hypersomnia. It also has neuroprotective effects in animal models of striatal neuropathology. Although the cellular mechanisms of action of modafinil are poorly understood, it has been shown to have a profile of pharmacological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central α1-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration. Modafinil,l-ephedrine andd-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substantial response rate decreasing effects. Little evidence was obtained that the discriminative stimulus effects of modafinil were produced by α1-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, modafinil andl-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil required very high doses: modafinil was over 200 times less potent thand-amphetamine and was also less potent thanl-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects and, like other abused stimulants, can serve as a reinforcer at high doses.
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  • 145
    ISSN: 1432-2072
    Keywords: Dorsal raphe nucleus ; Rat ; WAY-100635 ; 8-OH-DPAT ; Somatodendritic 5-HT1A receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the rat shock-induced ultrasonic vocalization test, the anxiolytic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) obtained after systemic (IP) and intracerebral injection into the dorsal raphe nucleus (DRN) were selectively abolished by pretreatment with the 5-HT1A receptor antagonist WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride]. This blockade was demonstrated both after systemic and DRN application of WAY-100635. Therefore, it is concluded that the anxiolytic effects of 8-OH-DPAT are mediated by activation of somatodendritic 5-HT1A receptors.
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  • 146
    ISSN: 1432-2013
    Keywords: Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 147
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    Pflügers Archiv 431 (1996), S. 882-887 
    ISSN: 1432-2013
    Keywords: Key words Contractile ; Staircase ; Calcium ; Rat ; Fast-twitch ; Fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Myosin light chain (P-LC) phosphorylation, which is thought to be the principle mechanism for twitch potentiation in skeletal muscle, is significantly decreased during staircase in fatigued muscle. Attenuated phosphorylation of P-LC could be due to either depressed Ca2+ transients in fatigue, or to some inhibitory influence of contractile activity on myosin light chain kinase (MLCK). Tetanic stimulation, which would presumably result in maximal activation of MLCK, could be used to evaluate these potential mechanisms. P-LC phosphorylation and twitch developed tension (DT) were assessed at 20 and 120 s following a tetanic contraction in either rested or fatigued rat gastrocnemius muscle in situ. P-LC phosphorylation was significantly lower in fatigued muscles (39.7 ± 3.2% vs 54.8 ± 3.5%, 20 s after a 2-s tetanic contraction), while posttetanic potentiation (PTP) was similar in fatigued (189.1 ± 6.5%) versus rested muscle (169.5 ± 2.6%). Tetanic DT was reduced following the fatigue protocol and, thus, the assumption that the MLCK system was fully activated by Ca2+ may not be valid. The potentiation-phosphorylation relationships were linear for both rested and fatigued muscles; however this relationship was shifted markedly leftward in fatigued muscles. It appears that during PTP, equivalent potentiation is attained with correspondingly lower levels of P-LC phosphorylation in fatigued muscle. This enhanced relative potentiation for a given level of phosphorylation could be expected if Ca2+ transients were attenuated in the fatigued muscle. However the results do not rule out the possibility that other factors contribute to potentiation under these circumstances.
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  • 148
    ISSN: 1432-2013
    Keywords: Key words Hypobaric hypoxia ; Physical training ; Skeletal muscle ; Muscle fibre type ; Fibre cross-sectional area ; Enzymes of energy metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adaptations of skeletal muscle morphology and metabolic enzymes were studied after prolonged training in and exposure to hypobaric (740 –770 mbar) as well as normobaric conditions in rats performing treadmill running training for 10, 21 and 56 days. Animals sacrificed after 91 days served as recovery groups from training and hypobaric exposure for 56 days. The rats were divided into normobaric sedentary (NS) and training (NT) groups and hypobaric sedentary (HS) and training (HT) groups. The weights of extensor digitorum longus (EDL) and soleus (SOL) muscles increased significantly in the 56HS and the 56HT groups compared with the 56NS group, the increase being greatest in the 56HS group. No differences in the mean fibre areas (MFA) of these muscles could be seen, whereas clearly reduced MFAs of type IIA and IIB were observed in the tibialis anterior (TA) muscle. However, fibre area distribution analyses in the EDL and TA muscles showed a higher proportion of larger fibers in the 56HS and 56HT groups than in the respective normobaric groups. On the contrary, in SOL muscles the proportion of smaller fibers was higher in the hypobaric than in normobaric groups at 56 days. Increased activities of citrate synthase and β-hydroxyacyl-CoA-dehydrogenase in SOL and TA muscles in the 56HT group indicate an increase in oxidative capacity. It is concluded that exposure to, and training in moderate hypobaric conditions leads to a positive muscle protein balance which is reflected in increased muscle weights. However, the sites of increased protein synthesis and the possible hyperplasia remain to be studied further.
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  • 149
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    Pflügers Archiv 432 (1996), S. 313-319 
    ISSN: 1432-2013
    Keywords: Key words Soleus muscle ; Rat ; Atrophy ; Unloading ; Motor units ; Contractile properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to compare the isometric contractile properties of rat soleus motor units after 14 days of hindlimb unloading (HU) to those under control conditions. The motor units (MU) were classified using two mechanical criteria: the presence or not of a sag during unfused tetani and the value of the twitch time-to-peak (TTP). Under control conditions, the soleus muscle was composed of 85% of slow-type (sag −, TTP 〉 20 ms) and 15% of fast-type (sag +, TTP 〈 20 ms) units. Following HU, these two populations were still present and results showed: (1) large decreases in their maximal tetanic tensions (of −67% and −60% for slow- and fast-type, respectively), and (2) changes in their relative proportions, i.e. a decrease in the percentage of slow-type units and a twofold increase in the percentage of fast-type units were observed. These latter changes might be the consequence of a complete transformation of slow-towards fast-type units. A third population appeared in the HU solei, 26% of the samples, combining the presence of a sag and speed-related properties between those of slow- and fast-type units. These slow-intermediate units might come from slow units partially transformed into a faster type during HU. Thus the present study showed that unloading conditions induced a reorganisation of the soleus motor unit profile. The complete or partial transformation of the motor units could be related to the changes in the electromyographical activity of the unloaded soleus.
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  • 150
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    Pflügers Archiv 431 (1996), S. 775-785 
    ISSN: 1432-2013
    Keywords: Rat ; Pancreas ; RIN cells ; Gap junctions ; Connexin43 ; Biophysical properties ; Voltage gating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A communication-deficient cell line (RIN cells, derived from a rat islet tumour), stably transfected with cDNA coding for rat connexin43 (Cx43), was chosen to further assess the mechanism of voltage gating of Cx43 gap junction channels. The experiments were carried out on preformed cell pairs using a dual whole-cell, voltage-clamp method. The junctional current,I j, revealed a time- and voltage-dependent inactivation at transjunctional voltagesV j 〉 ± 40mV When an asymmetrical pulse protocol was used (in cell 1 the holding potential was maintained, in cell 2 it was altered to establish a variableV j), the channels exhibited an asymmetrical gating behaviour:V j,O = −73.7 mV and 65.1 mV for negative and positiveV j, respectively (V j at whichI j is half-maximally inactivated); gj(min) = 0.34 and 0.29 (normalized minimal conductance); τ = 350 ms and 80 ms atV j = 100 mV (time constant ofI j inactivation). Hence, these parameters were more sensitive to positiveV j values. When a symmetrical pulse protocol was used (the holding potentials in cell 1 and cell 2 were altered simultaneously in steps of equal amplitude but of opposite polarity), theV j —dependent asymmetries were absent:V j,O = −60.5 and 59.5; gj (min) = 0.27 and 0.29; τ = 64 ms and 47 ms at 100 mV Putative explanations for these obervations are discussed. A possibility is that the number of channels alters with the polarity ofV j.
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  • 151
    ISSN: 1432-2013
    Keywords: Key words Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 152
    ISSN: 1432-2013
    Keywords: Nerve graft ; Magnification ; Motor nerve conduction velocity ; Compound muscle action potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Controversy surrounds the value of optic magnification for peripheral nerve surgery. The aim of this study was to compare the loupe magnification with microscope-assisted techniques in a rat tibial nerve graft model. The parameters studied included motor nerve conduction velocity (MNCV), clinical test equivalent (CTE), soleus muscle weight (SMW) and morphometric nerve indices. In the loupe and microscope groups MNCV mean was 26.77 ± 9.37 m/sec and 44.19 ± 11.36 m/sec respectively. MNCV results suggest better regeneration in the microscope group, as confirmed by CTE, SMW and myelinated fibre (MF) diameter.
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  • 153
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    Pflügers Archiv 433 (1996), S. 166-173 
    ISSN: 1432-2013
    Keywords: Key words Action potential ; Fatigue ; Ischaemia ; Muscle fibres ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The proximal and distal compartments of rat medial gastrocnemius muscle are dominated, respectively by, fast-twitch oxidative and fast twitch glycolytic fibres. In the present study it was hypothesized that repetitive in situ activation with an intact blood supply would cause greater declines in maximal tetanic force, compound action potential (CAP) amplitude and CAP area in the distal compared to the proximal compartment. Furthermore, it was hypothesized that these differences would be eliminated after occlusion of the blood supply to the muscle. A twitch followed by a tetanus (120 Hz, 200 ms duration) was given every 3 s for 2 min. This exercise protocol was applied once with, and once without, blood supply. During the first minute of the exercise, as expected, occlusion enhanced the decline of proximal force to 77.4 ± 0.8%, a level comparable (P〉0.05) to the decline of distal force (79.7 ± 1.2%). In contrast with the hypothesis, CAP amplitude was not significantly affected by occlusion and it changed significantly less in the proximal (to 102.9 ± 4.5%) compared to the distal (to 69.0 ± 6.7%) compartment. During the second minute of activation without blood flow, sudden declines of distal CAP amplitude (to 18.4 ± 3.4%) coupled with parallel declines in force (to 17.6 ± 2.8%) were observed to occur in the distal but not in the proximal compartment. Proximal final force and CAP amplitude were 54.2 ± 2.6% and 80.6 ± 5.9% respectively. Thus, in contrast with the hypothesis, occlusion enhanced the differences between compartments. These results are discussed in relation to fibre type composition and metabolic changes. It is suggested that a loss of force caused by a decreased muscle fibre excitability upon repetitive activation depends not only on fibre type, but also on the intramuscular location of the fibres.
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  • 154
    ISSN: 1432-2072
    Keywords: Nicotine ; Lobeline ; Stimulus discrimination task ; Cognition ; Memory ; Cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study evaluated the effects of two central nicotinic-cholinergic receptor agonists and an antagonist on performance accuracy of a rat, delayed stimulus discrimination task (DSDT). Rats were trained to discriminate between an auditory and visual stimulus by pressing a right or left lever. To diminish the rat's ability to use mediating spatial strategies to solve the task, computer automated, retractable doors separated the animal from the levers during delay intervals, thus reducing positioning at the lever. After stable baselines were achieved, rats were grouped and administered placebo (saline) and nicotine, lobeline or mecamylamine in a randomized dose series. Each group received two complete series of the selected compound on different occasions. Mecamylamine impaired DSDT accuracy in a dose-dependent manner while optimal doses of nicotine and lobeline significantly improved accuracy. Nicotine differed from lobeline in regard to its interaction with a dose of mecamylamine (1.0 mg/kg) that had not impaired DSDT accuracy. Combined administration of lobeline and mecamylamine was followed by a significantly increased level of DSDT accuracy that was similar to the improvement following administration of lobeline alone. In contrast, combined administration of nicotine and mecamylamine did not result in increased DSDT accuracy. Furthermore, lobeline administration similarly improved accuracy of trials associated with both the light and the tone, while nicotine improved accuracy of trials associated with the light to a much greater degree. These data suggest that the increases in DSDT accuracy associated with lobeline may be expressed through non-nicotinic mechanisms or a nicotinic receptor which is not blocked by mecamylamine.
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  • 155
    ISSN: 1432-2072
    Keywords: Amperozide ; FG5803 ; Haloperidol ; Antipsychotics ; Oral movements ; Chronic administration ; Acute administration ; Acute dystonia ; Tardive dyskinesia ; Extrapyramidal side effects ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term studies of antipsychotic-induced oral movements may serve as a rat model of acute and tardive movement disorders. Vacuous chewing movements (VCM), tongue protrusions (TP), and jaw tremors (TR) were studied in rats during acute and chronic administration of two potential antipsychotics, amperozide and FG5803. Comparisons were made with haloperidol and vehicle. Single intraperitoneal injections of amperozide (0.2, 1, or 5 mg/kg) or FG5803 (1.2, 6, or 30 mg/kg) were without effect on oral behaviors. During long-term drug administration, withdrawal and readministration, endpoint analysis was focused on changes in supranormal oral movements. The maximal mean control frequencies found at 29 sessions during 14 months experiment +2 standard deviations were used to define the upper limit of the normal range. FG5803 (1.2, 6, or 30 mg/kg per day) administered via the drinking water for 12 months, did not produce significant deviations from this normal range with respect to VCM, TP, or TR, and this drug was not studied further. Rats receiving amperozide (0.2, 1, or 5 mg/kg per day) showed dose-related increases in oral movements over the year. The changes began after 3 months of treatment with amperozide 1 and 5 mg/kg per day, but became statistically significant only during the second half of the treatment year. Amperozide 0.2 mg/kg per day did not produce significant changes in oral movements during administration for a year, but drug withdrawal resulted in a significant rise in TP behavior. Haloperidol (1 mg/kg per day) produced increases in supranormal oral movements which tended to level out after 9 months. In all groups with significant elevations (i.e. haloperidol and amperozide 1 and 5 mg/kg per day), there was a persistence of such movements during a month of drug withdrawal. During treatment with amperozide (1 or 5 mg/kg per day), some rats developed a high frequency chewing behavior up to 175 VCMs/min. It is concluded that long-term treatment with amperozide, but not FG5803, produced a tardive pattern of supranormal oral movements. The importance of these findings for the clinical future of amperozide is difficult to predict, due to the unexpected finding of high-frequency chewing, which has not been noticed before during extensive studies of classical neuroleptics.
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  • 156
    ISSN: 1432-2072
    Keywords: 7-OH-DPAT ; Apomorphine ; Dopamine ; D3 receptors ; Locomotor activity ; Progressive-ratio ; Quinpirole ; Rat ; Self-stimulation ; Stereotypies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effects of IP injections of (±) 7-hydroxy-2(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D3 subtype of receptor, on four behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self-stimulation of the ventral tegmental area (VTA), using the curve-shift procedure 3) operant responding for food under a progressive-ratio (PR) schedule and 4) induction of stereotypies. The effects of (±) 7-OH-DPAT were compared to the effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low doses (0.01–0.3 mg/kg), and only apomorphine had clear locomotor stimulant effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently depressed VTA self-stimulation in a similar way, with low doses inducing a fairly parallel rightward shift of the frequency/rate curves and higher doses flattening the curves. In contrast, responding for food under the PR schedule appeared to be differentially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a return to baseline levels with increasing doses (0.3–3 mg/kg); quinpirole showed a tendency to decrease responding over the whole dose-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists induced stereotypies, but there was a difference in the maximal stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower maximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies. Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at low doses, has depressant effects similar to those induced by low doses of the other two DA agonists. Differences in the behavioural effects of higher doses were, however, mostly observed in two procedures, PR responding and induction of stereotypies.
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  • 157
    ISSN: 1432-2072
    Keywords: d-Fenfluramine ; Metergoline ; 8-OH-DPAT ; WAY-100635 ; Anorexia ; Satiety sequence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These studies investigated the involvement of the 5-HT1A receptor in mediatingd-fenfluramine-induced anorexia in the rat. Non-deprived,d-fenfluramine-treated (3.0 mg/kg) rats consumed a reduced amount of a palatable wet mash and showed a temporal advance in the behavioural sequence consistent with satiety. Thus, rats treated withd-fenfluramine ceased feeding and began resting before corresponding controls. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (1.0 mg/kg) had no effect on either the reduced mash consumption or behavioural satiety sequence ofd-fenfluramine-treated animals at a dose which was found to attenuate the anorexia induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg). Pretreatment with the nonselective 5-HT antagonist metergoline (1.0 mg/kg) attenuated thed-fenfluramine-induced reduction of mash consumption and the advanced offset of feeding. Metergoline pretreatment had no effect on the advanced onset of resting observed ind-fenfluramine-treated animals. These data suggest thatd-fenfluramine reduces food intake, perhaps by enhancing satiety, via a mechanism which does not involve the 5-HT1A receptor subtype. The implications of these results to the utility of the behavioural satiety sequence as a measure of postprandial satiety are discussed.
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  • 158
    ISSN: 1432-0878
    Keywords: Key words: Growth factors ; Brain-derived neurotrophic factor ; Immediate-early genes ; Tyrosine hydroxylase ; Glia ; Cell culture ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Glial cell line-derived neurotrophic factor (GDNF) is a highly selective neurotrophic factor for midbrain dopaminergic neurons and might thus be of potential use in the therapy of Parkinson’s disease. In this study, we present evidence that the survival-promoting action of GDNF on dopaminergic neurons requires the concurrent activation of cAMP-dependent signaling pathways. In serum-free low density cultures of the dissociated embryonic day 15 mesencephalon, dopaminergic neurons undergo constant cell death as evidenced by a 90% reduction in tyrosine hydroxylase-immunoreactive (TH-IR) cell numbers between days 1 and 9 of cultivation. This decline was not affected by GDNF (5 ng/ml) within the initial 3 days of cultivation, but was in part attenuated with prolonged treatment. In contrast, stimulation of 3-day-old mesencephalic cultures with GDNF induced c-fos expression in 73% of all TH-IR neurons, indicative for the early presence of efficient signal-transduction coupling in these neurons. Combined treatment of mesencephalic cultures with dibutyryl cyclic AMP (dbcAMP; 100 μM) and GDNF accelerated the onset of the survival effects of GDNF on dopaminergic neurons, resulting in a 1.5-fold increase in the number of surviving TH-IR neurons at 3 days in vitro. In addition, activation of cAMP-dependent signal pathways significantly potentiated the survival-promoting effects of GDNF on dopaminergic neurons in older cultures. dbcAMP alone had no effect on dopaminergic cell survival. Taken together, our findings suggest that the action of GDNF on midbrain dopaminergic neurons is modulated by other extracellular signals.
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  • 159
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    Cell & tissue research 286 (1996), S. 249-255 
    ISSN: 1432-0878
    Keywords: Key words: GDNF ; NT-4/5 ; Tachykinin ; Dopamine ; Amphetamine ; PPT-A ; Survival ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Glial-cell-line-derived neurotrophic factor (GDNF) is a novel trophic factor with potent trophic effects on several neuron populations in the central and peripheral nervous system. In the present study, we have investigated and compared the potential of dopamine and metamphetamine with that of the two striatal neurotrophic factors, viz., GDNF and neurotrophin-(NT)-4/5, to regulate substance P and its preprotachykinin-A mRNA in organotypic striatal slices from postnatal (day 10) rats. Incubation for 2 weeks with 10 ng/ml GDNF significantly increased substance-P-like immunoreactivity determined by radioimmunoassay. Similarly, the corresponding preprotachykinin-A mRNA increased after 1 and 2 weeks of incubation, as analyzed by in situ hybridization. NT-4/5 exhibited similar effects.The dopamine-releasing agent metamphetamine stimulated substance-P-containing neurons in 1-week-old striatal slices, whereas dopamine stimulated substance-P-like immunoreactivity in 1- and 2-week old striatal cultures. The effects of dopamine and GDNF were not additive. We conclude that substance-P-containing medium-sized spiny neurons in the striatum are under both dopaminergic and growth factor control by GDNF and NT-4/5, which are both synthesized in the striatum. This adds a previously unknown role to those that have been established for GDNF in the nigrostriatal system.
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  • 160
    ISSN: 1432-0878
    Keywords: Key words: Mineralization ; Matrix vesicles ; Dentine ; Ultrastructure ; Element analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The purpose of this study was to elucidate the mineralization process of mantle dentine by ultrastructural and element-analytical investigation of matrix vesicles and successive stages. Upper second molars of albino rats were cryofixed and embedded in resin after freeze drying. Semithin dry sections were prepared for analyzing the calcium and phosphorus concentrations in the mineralized matrix vesicles or noduli, larger mineralized islands, and the mantle dentine. For ultrastructural studies, it was necessary to reduce section contact with hydrous fluids to a minimum in order to avoid preparation artifacts. The first mineral deposits were recognized as dot-like formations both in the interior of matrix vesicles and in association with the inner vesicle membrane. This indicated the existence of mineral nucleating sites located both at the inner membrane and at calcium-phosphate-binding macromolecules in the interior of the matrix vesicles. A significantly higher mineral content was found in mineralized matrix vesicles than in the mineralized extravesicular regions of the mineralized islands, suggesting the existence of a rapidly and densely mineralizing matrix in the matrix vesicles. A significant increase in mineral content per volume proceeding from the mineralized islands to mantle dentine suggested a further increase in the density of mineral.
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  • 161
    ISSN: 1615-6102
    Keywords: Aging ; Alzheimer's disease ; Brain ; Cell-free system ; Membranes ; Membrane trafficking ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A cell-free transfer system was used to measure capacity of brain membranes to support membrane renewal. To study transfer in brain, radiolabeled donor microsome fractions were prepared using brain slices from rats or frozen human brain autopsy specimens. Acceptor fractions, prepared from fresh or frozen rat brain or frozen human brain autopsy specimens, were immobilized on nitrocellulose. The complete reconstituted transfer system contained ATP plus ATP-regenerating system (or NADH) as a source of energy and brain cytosol. Slices of frozen brain incorporated acetate into membrane lipids with approximately the same efficiency as fresh brains. This efficiency declined with storage at 4 °C but only slowly. Donor fractions labeled with acetate from frozen slices exhibited specific transfer (37 °C minus 4 °C) of labeled membrane lipids with efficiencies comparable to fresh. The acceptor fraction could be prepared either from fresh or frozen material. Transfer was on the average two-fold stimulated by ATP at 37 °C compared to no ATP. Transfer also was stimulated by NADH. Analysis of linear transfer rates between 0 and 30 min revealed no significant effect of delay time or of time of prolonged storage on transfer efficiency beyond an initial decline of ca. 25% observed within the first two weeks after freezing. A decline of transfer was obtained with brains as the animals aged.
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  • 162
    ISSN: 1619-7089
    Keywords: Pinhole collimator ; Single-photon emission tomography ; High resolution ; Myocardial infarction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the accuracy of myocardial imaging by means of high-resolution single-photon emission tomography (SPET) with a pinhole collimator in rats with experimental infarction. Myocardial infarctions were induced in male Wistar rats by ligation of the left coronary artery for 30 min, followed by reperfusion. Two days after the reperfusion, pinhole SPET was performed after the intravenous administration of 111 MBq of thallium-201 chloride, using a rotating gamma camera equipped with a pinhole insert (2.0-mm aperture) in a low-energy pinhole collimator. SPET projection data were collected at 6° increments over 360° using a 4-cm radius of rotation to reconstruct the short- and long-axis images. Projection data were acquired in 15 or 30 s, the SPET imaging being accomplished within 40 min after the injection of201T1. After SPET, the rats were sacrificed to remove the hearts for autoradiography (ARG) and nitroblue tetrazolium (NBT) staining as a visual correlative study. Quantitative correlative studies between pinhole SPET and ARG were performed with linear regression analysis for infarct size and distribution properties (relative counts on SPET images and relative density on autoradiographs) on the short-axis sections. All infarcts (4 mm in minimum diameter) in seven rats were detected by pinhole SPET. The SPET images in rats with or without myocardial infarction were consistent with the findings of ARG and NBT staining. There were significant correlations between pinhole SPET and ARG with respect to the infarct size (r=0.933,P 〈0.001;n=15) and the relative radiotracer distribution (r=0.931,P 〈0.001; n=68). This study therefore confirmed the accuracy of myocardial pinhole SPET imaging in rats with myocardial infarction. This method may partially substitute for ARG and prove useful for assessing new myocardial imaging agents in vivo in small laboratory animals.
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  • 163
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    European journal of applied physiology 73 (1996), S. 130-135 
    ISSN: 1439-6327
    Keywords: Experimental auto-immune encephalomyelitis ; T-Cells ; Rat ; Auto-immunity ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P 〈 0.008) and the day of its maximal severity (P 〈 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P 〉 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P 〉0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.
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  • 164
    ISSN: 1439-6327
    Keywords: Short-term dietary change ; Glycogen Triacylglycerol ; Lipolysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of short-term diet change from high fat (F) to high carbohydrate (C) (or vice versa) on the storage and utilization of glycogen and triacylglycerol (TG) in muscle and liver were studied in untrained rats. Rats were fed on an F or C diet for 28 days. For an additional 3 days, half of the rats in both F and C groups were fed the same diets as before (F-F and C-C) and the other half of the rats were switched to the counterpart diets (F-C and C-F). On the final day of the experiment, half of the rats in each diet group were exercised by swimming for 1.5 h and the other half were rested. Short-term diet change from F to C diets increased, but the change from C to F diets decreased, glycogen stores of soleus and plantaris muscles and liver, resulting in no difference in glycogen stores between F-C and C-C, and between F-F and C-F. The dietary change also had an affect on TG stores of red gastrocnemius muscle and liver - however, muscle TG stores were still higher in F-C than in C-C and C-F, and there were no differences in liver TG stores between F-C and C-F. Exercise decreased muscle glycogen contents markedly in F-C and C-C, whereas, it decreased muscle TG concentrations in F-F and C-F. Liver glycogen depletion was lower in F-C than in other groups. Lipolytic activities of epididymal adipose tissue at rest and postexercise were no differences between F-F and F-C, and were higher in F-C than in C-C and C-F. β-adrenergic receptor binding was determined with [125I] iodocyanopindolol, and maximal numbers of β-adrenergic receptor of plasma membrane from perirenal adipose tissue were approximately 170%–200% higher in F-C than in other groups at rest and postexercise. These results suggested that short-term C diet fed rats adapted to F diet enhanced not only glycogen stores of muscle and liver but also did not decrease lipolytic activity of adipose tissue with increased β-adrenergic receptor density, resulting in the preservation of energy reserves (glycogen and TG) of muscle at rest, and liver glycogen sparing during exercise.
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  • 165
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    European journal of applied physiology 72 (1996), S. 496-501 
    ISSN: 1439-6327
    Keywords: Hyperthyroidism ; Glycogen ; Skeletal muscles ; Exercise ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine the rate of glycogen mobilization during exercise and the rate of the postexercise glycogen replenishment in different muscle types [white (WG), and red (RG) gastrocnemius, soleus (S) and diaphragm (D)] in rats treated with triiodothyronine (T3, group T). Rats of the control group (C) were treated with saline. The animals were made to run on a treadmill set at 0° gradient and at a speed of 1200 m·h−1. The time taken to reach exhaustion in group C was 188 (SD 23) min, whereas in group T, it was only 63 (SD 12) min. The content of glycogen in all muscles of the rats from group T at rest and during exercise was significantly lower than in group C at each corresponding time. At exhaustion, the glycogen content was in WG(C) 34.79 (SD 4.65), (T) 20.10 (SD 4.10); in RG(C) 22.82 (SD 4.66), (T) 16.50 (SD 2.00); in S(C) 14.85 (SD 2.48), (T) 11.90 (SD 2.93); in D(C) 18.18 (SD 3.49), (T) 7.54 (SD 3.36) (μmol of glucosyl units·g−1). The amount of glycogen mobilized during exhausting exercise in RG, S and D was similar in both groups whereas in WG it was much higher in rats of group T than in group C. The concentration of glycogen returned to pre-exercise values in each muscle 3 h after exercise. The net amount of glycogen resynthetized during 3 h of recovery depended on the muscle type. It was in WG(C) 3.30, (T) 18.03; in RG(C) 21.34, (T) 25.88, in S(C) 34.00, (T) 17.68, and in D(C) 17.25, (T) 12.22 μmol of glucosyl units·g−1 (each number represents the difference between the means). It concluded that treatment with T3 markedly affects this exercise-induced metabolism of glycogen in each muscle type. From our study it is suggested that low muscle glycogen content may contribute to a reduction in exercise performance in hyperthyroidism.
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  • 166
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    International urogynecology journal 7 (1996), S. 30-36 
    ISSN: 1433-3023
    Keywords: Aging ; Incontinence ; Rat ; Smooth ; Sphincter ; Striated ; Urethra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Muscles in the limbs change with age, but the aging process of urethral muscles is unknown. Therefore, we compared smooth and striated muscle content in the female rat urethra in young (12 month) and old (32 month) animals, using immunochemical techniques. All the striated skeletal fibers at both ages contain slow myosin. Urethral diameter does not change with age (young, 1.44±0.08 mm; old, 1.46±0.10 mm,n=5), nor does the external sphincter width (young, 0.088±0.016 mm; old, 0.080±0.017 mm,n=5). Neither smooth nor skeletal muscle volume in the urethra is changed with age (skeletal: young, 20.72±2.94%; old, 19.95±2.35%. Smooth: young, 22.26±2.98%; old, 26.75±2.35%,n=5). The external striated sphincter is separate and distinct from the pubococcygeal region of the levator ani muscle, but is closely apposed to another layer of longitudinally oriented fibers into the vaginal musculature. The morphometric analysis shows no difference in urethral architecture in aging female rats.
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  • 167
    ISSN: 1438-8359
    Keywords: Cervical sympathectomy ; Gonadotropin-releasing hormone ; Hypothalamus ; Median eminence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine the effects of cervical sympathectomy on the transport of gonadotropin-releasing hormone (GnRH) between the hypothalamic neurons and the median eminence, 16 male rats were assigned into four groups: control (C), light (L), light-sympathectomy (LS), and light-colchicine (LC). The C group was kept under a normal circadian rhythm for 2 weeks, and the L group was kept under continuous exposure to light for the same period. The LS group underwent bilateral cervical sympathectomy before being kept under continuous light conditions for 2 weeks. The LC group received colchicine into the cerebral ventricle after being kept under continuous light for 12 days; subsequently, this group was also housed for 2 days under continous light. After these procedures, blood was collected and serum luteinizing hormone (LH) levels were measured. All rats were perfused with a fixative, and GnRH neurons around the anterior commissure, as well as GnRH fibers and granules in the median eminence, were stained immunohistochemically. The L group showed a decreased number of GnRH neurons, increased concentrations of GnRH fibers and granules, and an increased LH level; however, in the LS and LC groups, these changes were not seen. The response in the LS group resembled that in the LC group. Considering the action of colchicine, which inhibits axonal transport, it is suggested that cervical sympathectomy also inhibits axonal transports of GnRH between the GnRH neurons and the median eminence during continuous exposure to light.
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  • 168
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 214-221 
    ISSN: 1434-4726
    Keywords: Formalin fixation ; Mucous cell ; Submandibular gland ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the pennuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissue as quickly as possible.
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  • 169
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 142-146 
    ISSN: 1434-4726
    Keywords: Immunocompetent cells ; Mucosal immune system ; Larynx ; Immunohistology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The larynx can be divided into a supraglottic, a glottic and a subglottic area, each serving different functions. In many cases of laryngitis the site of infection is located in one area, leaving other areas unaffected. It seems reasonable to speculate that the underlying cause of the heterogeneous infection pattern in the larynx is the different processing of infectious agents. Therefore, the number and distribution of granulocytes, macrophages, dendritic cells, natural killer cells and T and B lymphocytes in the normal laryngeal mucosa of young rats were studied. The results show that, with the exception of granulocytes, all subpopulations were present in different numbers. Many macrophages and dendritic cells but only a few natural killer cells and T and B lymphocytes were located in the mucosa. Dendritic cells, natural killer cells and T and B lymphocytes were rarely present in the vocal fold area, whereas in the subglottic area they were present in high numbers. Thus, differences in the composition of immunocompetent cell populations between laryngeal areas were detectable.
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  • 170
    ISSN: 1434-4726
    Keywords: Endolymph potassium ; Ion-selective microelectrode ; Noise exposure ; Deafness ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Double-barrelled potassium selective microelectrodes (K-ISME) were used in situ for real-time sequential determinations of potassium concentrations (CK+) in endolymph, marginal cells and the spiral ligaments of rats exposed to moderate noise at 100 dB for 30 min (NE) and control (CTL) animals. CK+ in NE animals at these sites did not differ significantly when compared to CK+ in CTL animals. However, there was a slight decrease in CK+ in marginal cells in the noise-exposed animals.
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  • 171
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    Medical molecular morphology 29 (1996), S. 28-36 
    ISSN: 1860-1499
    Keywords: Swimming test ; Skeletal muscle ; Rat ; Temperature ; Light and electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural changes in rat skeletal muscle induced by swimming to exhaustion were investigated by light and electron microscopy. Male Wistar rats were divided into four groups: a 28°C swimming groups, a 42°C swimming group, and non-swimming control groups at each of these temperatures. The experimental animals were tested in water for 32 min. Immediately after the swimming test, under pentobarbital intravenous anesthesia, the extensor digitorum longus muscle (EDL) and the soleus muscle (SOL) of each animal were removed from the right hindleg. Light microscopy revealed structural changes such as atrophy and focal necrosis in both muscles in animals swimming at 28 and 42°C. In some animals swimming at 42°C, an inflammatory reaction was noted around severely necrotic lesions in the EDL. A few structural changes indicative of mild atrophy were observed in the control animals. Electron microscopy revealed swelling of the sarcoplasm, swelling of the mitochondria, and disorganization or disappearance of myofilaments in various degrees in the atrophic and focal necrotic muscles of the animals swimming at 28 and 42°C. The degree of these structural changes in skeletal muscle fibers was more conspicuous in the animals swimming at 42°C than at 28°C, and more marked in the EDL than in the SOL.
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  • 172
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    Communications in Numerical Methods in Engineering 12 (1996), S. 13-20 
    ISSN: 1069-8299
    Keywords: open channel flows ; Riemann solver ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: An efficient numerical method is developed for the one-dimensional open channel flow equations. The scheme is a modification of one presented recently, but with an improvement in the efficiency made through the use of the arithmetic mean as an average of flow variables across the interface between adjacent states. Numerical results are shown for two problems, and an indication of the efficiency gained is given.
    Additional Material: 6 Ill.
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  • 173
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    Communications in Numerical Methods in Engineering 12 (1996), S. 21-29 
    ISSN: 1069-8299
    Keywords: finite element systems ; elliptic partial differential equations ; approximate LU factorization ; explicit matrix inversion ; preconditioning ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A new class of explicit generalized approximate inverse finite element matrix algorithmic methods, based on the concept of LU-sparse factorization procedures, without inverting the decomposition factors, has recently been introduced. The large sparse unsymmetric coefficient matrix of irregular structure is factorized approximately and, in conjunction with approximate inverse matrix techniques, yields explicit preconditioned methods for the finite element (FE) and finite difference (FD) method. The numerical implementation of these algorithms is presented and Fortran subroutines for the efficient solution of the sparse unsymmetric linear systems are given.
    Additional Material: 1 Tab.
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  • 174
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    Communications in Numerical Methods in Engineering 12 (1996), S. 147-148 
    ISSN: 1069-8299
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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  • 175
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    Communications in Numerical Methods in Engineering 12 (1996), S. 149-150 
    ISSN: 1069-8299
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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  • 176
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    Communications in Numerical Methods in Engineering 12 (1996), S. 63-73 
    ISSN: 1069-8299
    Keywords: asymptotic solution ; natural frequencies ; membrane vibrations ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: In the paper an asymptotic formula has been developed to correct the discretization error for the finite element predicted natural frequencies of membrane transverse vibration problems. The general idea behind deriving this asymptotic formula is that, when the finite element size approaches zero, a discretized finite element system approaches a continuous system and the predicted natural frequencies of the system from the finite element analysis therefore approach the exact solutions of the system. Without losing generality, several different finite element mesh patterns have been considered and the same asymptotic formula for correcting the finite element predicted natural frequency has been obtained for all the different mesh patterns because of the uniqueness of the exact solution to the natural frequency of a real structure. The usefulness, effectiveness and efficiency of the present asymptotic formula have been assessed by a simple but critical problem, for which the exact solution is available for comparison. In order to investigate the applicability of the asymptotic formula to practical engineering problems, two challenging membrane vibration problems of irregular shapes, an L-shape and a tapered shape with a circular hole in the centre, have also been analysed. The related numerical results have demonstrated that the asymptotic formula provides a very useful post-processing error corrector for the finite element predicted natural frequencies of membrane transverse vibration problems, even though the problem domains are of irregular shape. The greatest advantage in using the present asymptotic formula is that it yields a solution of higher accuracy, by simply using the formula to correct the rough solution obtained from a much coarser finite element mesh with fewer degrees of freedom, without any further finite element calculation.
    Additional Material: 7 Ill.
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  • 177
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    Chemical Engineering & Technology - CET 19 (1996), S. 137-142 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The equilibria and kinetics of adsorption of lysozyme and bovine serum albumin on the Fractogel-EMD tentacle-type cation exchanger and the Fractogel-TSK conventional cation exchanger have been studied experimentally by batch stirred-tank method. Adsorption equilibrium data corresponded well to the Langmuir isotherm. For both proteins, the tentacle-type exchanger exhibited a higher binding capacity than the conventional exchanger. This is attributed to the flexibility of the functional groups in the tentacle-type exchanger which enhance optimal electrostatic interactions. The dynamic data were analyzed by a simplified data model which lumped mass transfer resistances and intrinsic adsorption kinetics into a single rate constant. For both proteins, it was found that the tentacle-type exchanger showed a smaller lumped rate coefficient than the conventional exchanger. The difference in the values of the lumped rate coefficients was shown to be due to the influence of nonlinear equilibrium constants rather than due to any difference in rate of adsorption.
    Additional Material: 5 Ill.
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  • 178
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    Chemical Engineering & Technology - CET 19 (1996) 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 179
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The paper briefly reviews the historical development of exergoeconomics, the existing methodologies, and their application. Particular emphasis is placed on the optimization of the design of new energy-conversion systems.
    Additional Material: 1 Ill.
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  • 180
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A critical comparison of the strength and weakness of two optimization strategies for thermochemical process is made, i.e. pinch analysis and exergy analysis. Although both methods have a unique root, i.e. the minimization of the exergy losses, pinch analysis has evolved to become an instrument of direct and optimal design of a heat exchanger network while exergy analysis as such does not give an indication about process optimization. In combination with an adequate simulation code of a process, however, it can help to find the optimum process structure.
    Additional Material: 5 Ill.
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  • 181
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    Chemical Engineering & Technology - CET 19 (1996), S. 215-221 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The growth of a thin liquid film surrounded by gas pocket(s), undergoing absorption with a zero-order chemical reaction, has been simulated by an apt mathematical model in order to study the influence of various parameters involved. The solution has been obtained semi analytically using Goodman's integral method and solving the resulting differential equation by a fourth-order Runge-Kutta numerical integration algorithm. The computations reveal the strong dependence of film growth on reaction rate, diffusivity, and molar volume whereas the effect of gas-pocket volume and initial film thickness are moderate.
    Additional Material: 7 Ill.
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  • 182
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The optimal layout of a chemical plant is determined by both economic and environmental aspects. The mathematical approach to this problem is given by representing the process through a superstructure, including any foreseeable process topology. It is described by integer variables, whereas real variables arise from the unit models and the thermodynamic calculations. By including process constraints and an objective function, a Mixed Integer Nonlinear Programming (MINLP) optimization problem is postulated. In this paper MINLP algorithms are combined with a technique for the exergy analysis of chemical processes for the preliminary screening of process alternatives. The exergy analysis as a screening technique is advantageous due to a significantly smaller amount of required data and computing time, compared with true optimization, including cost estimation at an earlier stage of process synthesis and analysis. Thus, a broader solution space can be examined. The subsequent cost analysis has then only to be focused on a reduced set of parameters.
    Additional Material: 5 Ill.
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  • 183
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    Chemical Engineering & Technology - CET 19 (1996), S. 243-248 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Heat transfer from a buried pipe carrying a flowing liquid is analysed using a 3-dimensional geometry, transient modeling and numerical methods. The pipe is buried horizontally in soil whose initial surface temperature is assumed to be below that of the bulk soil and the pipe, and also below the freezing temperature of the liquid. The problem is solved using string-intersected-boundaries and a three-level alternating-direction-implicit finite-difference method. It is possible to predict the time taken for the fluid anywhere in the pipe to fall to its freezing point. The minimum burial depth needed so that the pipe does not freeze is also predicted. The simulation was run on an ordinary mainframe computer with very small computation times. The package developed can be used by designers such as pipeline, plant and water distribution engineers.
    Additional Material: 7 Ill.
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  • 184
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    Chemical Engineering & Technology - CET 19 (1996), S. 272-282 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A chain growth model for heterogeneous secondary reactions is developed for the pyrolysis of large wood particles and the parameters determined by nonlinear optimization. The model takes both the volatile retention time and cracking and repolymerization reactions of the vapours with the decomposing solid as well as sutocatalysis into consideration. The extent of the secondary reactions is strongly influenced by the time and the ratio of the autocatalytic (propagation) reaction rate to noncatalytic (initiation) reaction rate. The wood which has a higher value of the autocatalytic/noncatalytic ratio also has a higher exothermic heat of reaction and yields a higher amount of final char residue. This fact confirms the heterogeneous secondary reactions lead to carbon enrichment of the final residue and are accompanied with an exothermic heat of reaction. The lower activation energies of the initiation and propagation reactions as compared to primary reactions (competitive reaction model consisting of weight loss and char forming reactions) confirm autocatalysis in large particles. The sealed reactor studies of small quantities of fine wood samples show that heterogeneous secondary reactions and not lower heating rates in large particles are the main source of char formed during the thermal decomposition of large wood particles. The model predictions are in agreement with the weight loss and temperature versus time curves over a wide range of particle size and furnace temperatures.
    Additional Material: 10 Ill.
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  • 185
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    Chemical Engineering & Technology - CET 19 (1996), S. 315-323 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Intermig impellers have been postulated as very efficient for mixing highly viscous non-Newtonian fluids (such as xanthan and mycelial broths). However, no formal characterisation has been published and no fair comparisons have been made, based on accurate power drawn measurements and using equal number of impeller stages and equal diameter, if compared (for example) with the performance of Rushton turbines. Characterisation of the shape, size, and evolution of the well-mixed zones or “caverns” were correlated with power drawn, for single and dual Rushton turbines and for one- as well as two-stage Intermig unslotted impellers. Cavern evolution studies were carried out in a mixing tank (diameter=0.205 m, H/T=1.6) equipped with an accurate air bearing dynamometer. Carbopol 940 (0.25 wt.-%) was used as a model, transparent fluid. Impeller to tank diameter ratio was 0.53 for both impellers. Caverns were visualised by injecting methylene blue in the well-mixed zones. A single Rushton turbine developed larger caverns if compared with one-stage Intermig of the same diameter under power drawn below 1.5 kW m-3. At higher power drawn, both impellers behaved very similarly, reaching a limit in cavern volume of about 40% of the total liquid volume, even at very high (20 kW m03) power drawn. A similar trend characterised dual combinations: below 3 kW m-3, dual Rushtons gave larger cavern volume if compared with the performance of two-stage Intermigs. In either case, power drawn higher than 3 kW m03 was sufficient to mix more than 90% of the liquid volume. The presence or absence of the slot in the Intermig did not influence cavern development. Experiments with a smaller if compared with those obtained with the larger Intermig (D/T = 0.53).
    Additional Material: 11 Ill.
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  • 186
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Heat exchanger network synthesis (HENS) is a frequently encountered class of chemical engineering optimization targets. Besides its immediate relevance to practical, industrial applications, the HENS problem presents an adequate complexity class to test new technique of numerical optimization and benchmark them.This paper first sketches two established approaches to HEN optimization. The fist one is based on thermodynamic insight, while the second one uses MINLP techniques for rigid optimization. Afterwards an alternative approach based on the paradigm of evolutionary optimization is introduced. The newly developed optimizer module is coupled to the well known ASPEN PLUS simulator. The program package allows the optimization of parameters as well as network structure.
    Additional Material: 5 Ill.
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  • 187
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    Chemical Engineering & Technology - CET 19 (1996), S. 197-202 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Interfacial properties exert a fundamental influence on fluid/liquid separation processes, with the interfacial tension being an important quantity associated with mass transfer and mutual solubility of participating compounds. A better understanding of transport phenomena is achieved by obtaining interfacial tension data under different conditions of pressure and temperature and as a function of time. Generally, interfacial tension decreases with increasing pressure due to increased adsorption of the compressed fluid at the interface. In the case of considerable mutual solubility, interfacial tension further decreases with time as mass transfer into the bulk phase proceeds. Prediction of colloidal behaviour in a separation process requires acquisition of additional information on the presence of surfactants.
    Additional Material: 10 Ill.
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  • 188
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    Chemical Engineering & Technology - CET 19 (1996), S. 448-455 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A mathematical model has been developed to simulate the operation of an absorption-driven multiple-effect evaporator. The model is based on mass and enthalpy balances and heat transfer rate equations of the various components of the system. The model has been validated by comparing model predictions to experimental results from the operation of a four effect absorption-driven falling film evaporator coupled with a two-effect regenerator which operated using solutions of sodium hydroxide as an absorptive medium. The model predictions are in satisfactory agreement with the experimental results.
    Additional Material: 10 Ill.
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  • 189
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    Chemical Engineering & Technology - CET 19 (1996), S. 467-472 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Knowledge of the compression factor is essential for the transport, storage and utilization of natural gas. The normal way to determine this property is by using an equation of state (EOS) which utilizes the gas temperature, pressure, volume, and composition. In many industrial situations, the composition of the natural gas is not available, yet it is still necessary to calculate the compression factor. In this paper, we present an EOS which uses relative density, heating value, and diluent compositions to determine the compression factor. The applicable ranges of conditions are 220 to 500 K up to 70 MPa (-60-450°F up to 10,000 psia). The calculations agree with data within 0.1% average absolute deviatation up to 10 MPa with a maximum deviation of 1.9% near pure component critical points or mixture cricondentherms. The equation also extrapolates through data up to 70 MPa within 1.9% We present comparisons to data of AGA Report No. 8 and to data in the paper.
    Additional Material: 2 Ill.
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  • 190
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Complex configurations of distillation columns have been shown to consume less energy than simple configurations. These complex configurations mainly results from two considerations: either a feed split, where the condensing vapor from the top of the high pressure column is used to heat the reboiler of the low pressure column, or the overheads from a high pressure column in a distillation train used to reboil a column under lower pressure. Industrial experience shows that very often in these configurations there is still incentive for more energy reduction simply because of inefficient control. The energy integration increases the control loop coupling the system, so that the operating strategy for the columns is no longer apparent. Therefore, the dynamic behaviour and the operational constraints of such systems become very important. The use of rigorous dynamic model of the processes is an essential instruments to pursue the goal of good and reliable process control Such models allow the engineer to realistically simulate the process with the desired control system in place and to analyze the effects of equipment sizing, hest integration, and disturbances. Variable pairing proved is used to illustrate that effective control of energy-integrated distillation columns can be achieved by proper selection of manipulated variables and pairing them correctly with control variables. Hints will also be given, when multivariable predictive control schemes should be used.
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  • 191
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    Chemical Engineering & Technology - CET 19 (1996), S. 514-525 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Many rectification processes are used to separate corrosive substances with high boiling points. This reports deals with a new type of structured column pacing mode of corrosion-resistant carbon fiber material. These column internals allows for low pressure drop at high throughput rated with reasonable column efficiency. Experiments in columns of 50 and 100 mm diameter have been carried out to investigated separation efficiency, pressure drop and liquid holdup of the packing even at low operation pressures. In the respective columns twp geometrical different types of packing have been tested using binary mixtures of chlorobenzene/ethylbenzene with a packing geometry similar to the Sulzer EX packing, the 100 mm diameter column was filled with elements of rougher structure and smaller specific surface. Basing on the experimental results, model equations are presented, which allow the calculation of the investigated performance characteristics.
    Additional Material: 14 Ill.
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  • 192
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    Chemical Engineering & Technology - CET 19 (1996), S. 432-437 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The wetting characteristics of fine powders play an important role in a variety of processes. The most important way of characterising the wettability of a fluid/fluid/solid system is to measure the contact angle. This paper describes a relatively simple method for the determination of the contact angle on powdery materials. The technique involves the measurement of the dynamic contact angle which is formed when a liquid drop is placed on a horizontal porous surface. On the basis of the measured dynamic contact angle as a function of time an “apparent” static contact angle has been defined, which gives a measure of the wettability of porous solid systems by analogy with the wetting of non-porous solids. Determinations with glass beads and NaCl-powders as the test materials indicate that the measured value depends on the particle size of the powder, the porosity and the temperature. It was concluded that the capillary penetration of the liquid droplet into the porous media itself influences the wetting characteristics.
    Additional Material: 12 Ill.
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  • 193
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    Chemical Engineering & Technology - CET 19 (1996), S. 456-461 
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A new reactive distillation device, the multistage gas/liquid/solid three-phase fluidized bed, has been developed. The flow regimes of the multistage three-phase fluidized bed have been studied and the regimes can be divided into the liquid leakage regime, the dispersed bubble regime, and the coalesced bubble regime. Liquid velocity has a much smaller effect on phase holdups in this device than in conventional three-phase fluidized beds. The three phase fluidized bed is used as a reactive distillation device for the hydrolysis of methyl acetate. Much higher reaction conversion than the equilibrium value and high catalyst-contacting efficiency are obtained. Different methods of feeding the water into the reactive distillation section are studied.
    Additional Material: 9 Ill.
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  • 194
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Chemical engineering analysis using entropy production has been proven to be an essential tool to identify areas in chemical plants, where degradation of energy occurs. Though, applied very extensively in the area of heat exchanger networks in the form of “pinch technology”, the method is rarely used with respect to processes with mass energy. Entropy productions in destillation columns have been evaluated and discussed with respect to feed introduction, sequences of columns and other technically important features.
    Additional Material: 12 Ill.
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  • 195
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Exergy analysis is an excellent tool for locating weak spots in a process. Purposefully applied, it improve our insight and allow us to design processes systematically. Yet for many engineers exergy remains a difficult subjects. To make analysis easier and the results easier to interpret, therefore, we need the best possible exergy analysis tools. The commercial performance of both plant suppliers and operating companies depends heavily on optimization to reduce plant costs (in the widest sense) to a minimum. As an optimization tool in plant design, exergy analysis has to compete with parametric studied and, increasingly, with equation-based optimization programs.
    Additional Material: 5 Ill.
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  • 196
    ISSN: 0930-7516
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: This paper presents results of temperature-programmed desorption (TDP) as a method for studying the acid and shape-selective properties of small- and intermediate-pore zeolites.A combination of an in situ infrared spectrometer and a downstream gas chromatograph for analyzing the desorption products is used to detect the desorption process. This is followed by a separate, newly installed microbalance facility.The studies shows that a part of the amines, esp. dimethylamine (DMA) and trimethylamine (TMA), adsorbed on the zeolites undergo decomposition, disproportionation and carbonization reaction during the TDP measurements at elevated temperatures. Comparison of the microbalance measurements and the gas chromatographic results give a good picture of the extent of these reaction.
    Additional Material: 20 Ill.
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  • 197
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    Particle and Particle Systems Characterization 13 (1996), S. 309-312 
    ISSN: 0934-0866
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Experimental investigations were carried out with mainly a Mogensen-Sizer, compared with test screening and additionally laser diffraction and light extinction, in order to check the qualification for on-line determination of particle size distribution under the specific conditions of feed milling. The different components of compound feed, the degree of milling, the difference in measured particle characteristics and the possibility of sample dispersion affect the comparability of the results. The results show that laser diffraction is a manysided method with accurate recording of the distribution. The modified Mogensen-Sizer can be a robust low-price alternative if the control of selected distribution parameters is sufficient.
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  • 198
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    Particle and Particle Systems Characterization 13 (1996), S. 301-308 
    ISSN: 0934-0866
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Laser diffraction (LD), with reference to the analysis time, is highly advantageous for the automation of particle size analysis. The high measuring frequencies alloy quasi-continous measuring operation. The fineness values obtained form the particle size distribution (PSD) can be transformed into electrical signals for automatic process control.For industrial purposes, an encapsulated measuring cell was developed where the laser beam penetrates the dispersed fines stream via two optical windows. Thus, hazardous materials can also be measured, specifically pharmaceutical or chemical products, or applications requiring explosion-proof plant design are possible. Great efforts had to be made to keep the inner side of the windows clean form product dust. Ultimately, batches running for more than 8 h could be analysed continuously without any contamination of the windows. For the PSD measurements, a standard LD instrument was used with a measuring range of 0.5/0.9-175 μm.As product fineness is monitored continuously in-stream, and virtually without delay, any changes in the fineness during classifier operation can be detected immediately. On the one hand, this opens up a new field for studies of classifier performance. On the other, immediate quality control of even very small batches is possible during the micronization process. The results demonstrate very clearly, for example, the importance of controlling the feed rate to the classifier. Therefore, fineness control by means of this in-line technique gives superior advantages for direct adjustment of the classifier speed.
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  • 199
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    Particle and Particle Systems Characterization 13 (1996), S. 313-321 
    ISSN: 0934-0866
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The precipitation of barium sulfate was investigated by photon correlation spectroscopic (PCS) measurements of the growing crystals combined with electrical conductivity measurements of the mother solution. Small silica seeds (36nm) were added to the solution. Therefore, heterogeneous nucleation did not take place on the walls and on the stirrer, which is usually the case, but on the seeds. Hence the growth of the crystals which had nucleated on the seeds could be studied by PCS. In order to avoid the ill-conditioned inversion of the measured raw data, the autocorrelation functions, a population balance model was used to calculate these functions with the help of a kinetic model taken from the literature. The measured an the calculated autocorrelation functions could coincide and adjustable parameters were found from a least-squares fit. The measurements revealed that nucleation is strongly enhanced by PMA-PVS (polymaleic acid-polyvinylsulfonic acid). However, a simple model which assumes langmuir adsorption of PMA-PVS on the crystal surface did not describe the kinetics very well. The nucleation rate in the absence of the additive was found to be J=1.3·1010 exp(-27/In2S) [m-3s-1], while the growth rate was G=2.6·10-8(S-1)2/3 S1/3 exp(-29/3 In S) [ms-1]. These results match results taken from the literature fairly well.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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  • 200
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Particle and Particle Systems Characterization 13 (1996), S. 322-326 
    ISSN: 0934-0866
    Keywords: Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: During the spherical agglomeration process, a suspended solid is agglomerated by adding a binding liquid. First, mircoagglomerates or flocs are produced, which are compacted in the course of the process. Agglomerate size was evaluated by laser diffraction spectrometry, image analysis was used to determine the size and some adequately defined shape parameters calculated by Fourier analysis of the particle contour.The shape analysis confirms the visual observations; the compaction of the flocs is expressed by the corresponding change of the shape parameters. The influence of several process parameters on changes in agglomerate shape can be described quantitatively and help to gain an insight into agglomeration mechanisms. The particle size distributions determined by image analysis and laser diffraction spectrometry hardly differ for fairly spherical flocs or agglomerates. Concerning the size distribution of the irregular flocs, laser diffraction spectrometry measures larger particles than image analysis.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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