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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 26 (1984), S. 297-299 
    ISSN: 1432-0428
    Keywords: Rat ; pathogenesis ; insulin-dependent diabetes ; dietary proteins ; milk proteins ; wheat proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Animals from a colony of spontaneously diabetic insulin-dependent BB rats were fed from weaning with semisynthetic diets in which natural proteins were replaced by l-amino acids with or without the addition of either milk or wheat proteins. The normal 50% incidence of diabetes in the colony was reduced to 15% in rats fed the basic semi-synthetic diet, while it was 35% and 52% when supplemented with gluten or milk, respectively. Thus, dietary factors might precipitate the expression of the disease.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 169 (1984), S. 271-274 
    ISSN: 1432-0568
    Keywords: Scanning electron microscopy ; Pericyte ; Skin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Surface morphology of pericytes of the subepidermal capillary network of rat skin was studied by scanning electron microscopy. Pericytes showed considerable variation in shape, one end of the spectrum representing a fusiform cell body and lateral projections, the other end a club-like, undulated appearance. Most cells of whatever form were disposed parallel to the capillary course and aligned on the dermal side of the vessels. The pericytic processes encompassed up to half of the endothelial circumference, and were not tapered but spatulated at the ends; the cells adhered to the vessel wall only in certain areas. These findings, together with our previous observation that the subepidermal capillaries exhibit fenestrations mainly at the epidermal side of the endothelial lining, suggest a possible functional role of the pericyte in control of material exchange through the vessel wall. The lateral processes of the fusiform pericytes may, by contraction, cause thinning of the capillary endothelium and the formation of fenestrae, while the club-like pericytes may straighten and push the capillary towards the epidermis, if pericytes are indeed contractile cells, as recent studies indicate.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 170 (1984), S. 79-85 
    ISSN: 1432-0568
    Keywords: Perineuronal net ; Astrocytes ; Fastigial nucleus ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphological study of the rat fastigial nucleus with the Golgi-Rio Hortega method showed the presence of glial perineuronal nets surrounding the large neurons, but not the small ones. This perineuronal net appeared as a mesh of tenuous glial processes which covers the neuronal perikarya and proximal dendrites. The small alveolate compartments in this mesh seem to correspond to the holes for the synaptic boutons. Our results also indicate that the perineuronal net is derived from interneuronal protoplasmic and velate astrocytes. Using camera lucida drawings of this perineuronal net we have made a quantitative estimation of the size and density of synaptic boutons on these large neurons. The average numerical density of synaptic boutons was about 19 per 100 μm2 of the neuronal surface, the mean area of the synaptic holes being 2.5 μm2. Furthermore, the quantitative data evidence that about 52.5% of the neuronal surface is presumably occupied by synaptic boutons whereas the remaining 47.5% is covered by the glial processes of the perineuronal net. Semithin sections prepared from thick Golgi sections were used for the cytological study of the neurons surrounded by this glial pericellular network. The possible functional significance of the perineuronal net in the regulation of synaptic transmission in the fastigial cerebellar nucleus is briefly discussed.
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  • 4
    ISSN: 1432-0568
    Keywords: Splenius muscle ; Muscle fiber types ; Primary afferents ; Spinal cord ; Brain stem ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The splenius muscle of the rat was investigated with regard to its structure and innervation. The latter was compared with that of the quadriceps muscle. The results can be summarized as follows: The splenius muscles of both sides form a bipennate muscle plate connecting the occipital bone with the spinous process of the second thoracic vertebra. The lateral parts of both muscles are attached directly to this prominent bony process, whereas the medial parts end in a median raphe which forms a tendinous cranial extension of the second thoracic vertebra. This tendinous extension, showing no connection to the cervical vertebrae, serves also for the attachment of acromio-trapezius muscle fibers. The lateral part of the splenius muscle is divided into two parts by a tendinous intersection. The splenius muscle consists mainly of fast twitch fibers: 55% were characterized as IIB and 40% as IIA fibers by histochemical demonstration of myosin ATPase-activity. A high content of muscle spindles — 57 spindles per gram of muscle tissue — was found. Comparing several aspects of the innervation of the splenius to that of the quadriceps muscle, the following results could be obtained: 1. The ratio of motor end plate size to muscle fiber volume is significantly higher in the splenius than in the quadriceps muscle. 2. As demonstrated by transganglionary HRP-transport, the main part of labeled splenius afferents to the spinal cord terminates in the central cervical nucleus. Quadriceps afferents, entering the lower thoracic and upper lumbar segments, mainly end in the area of Clarke's column. Several labeled fibers descend to the sixth lumbar and first sacral segments, where they terminate in the area of Stilling's nucleus. 3. A group of primary afferents from both muscles-most probably III- and IV-afferents — projects to the dorsal laminae of the dorsal horn; terminals from the splenius are accumulated in the lateral parts of these laminae, where-us those of the quadriceps are more concentrated in the medial areas. 4. Within the brain stem, most afferents from the splemus terminate in the external cuneate nucleus. Most of the quadriceps afferents course to the gracile nucleus. 5. Terminals from both muscle nerves were found in the area of the spinal vestibular nucleus. In conclusion, the most conspicuous results were: 1) Besides the segmental projection to the dorsal horn there is an almost exclusive projection of splenius primary afferents to relay nuclei to the cerebellum. 2) The relatively high ratio: end plate size/muscle fiber volume, which is characteristics of finely adjusting muscles. These results provide additional clues to the understanding of the particular role of the neck muscles in posture and head movement.
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  • 5
    ISSN: 1432-0568
    Keywords: Somatostatin ; Neurotensin ; Immunohistochemistry ; Septum ; Basal forebrain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies to the neuropeptides somatostatin (SOM) and neurotensin were used to study the distribution of the two peptides within the septum of the rat brain. In colchicine treated rats, numerous somatostatin-positive cell bodies were found in the dorsal and ventral subdivisions of the alteral septum, along the border of the nucleus accumbens, in the ventral tip of the horizontal limb of the diagonal band of Broca as well as in the anterior hippocampal rudiment, infralimbic area and several other structures of the basal forebrain (e.g., nucleus accumbens, olfactory tubercle and substantia innominata). Cell bodies containing immunoreactivity for neurotensin were situated in the intermediate and ventral subdivisions of the lateral septum, the medial septal nucleus, the diagonal band of Broca, the rostro-medial continuation of the substantia innominata and the olfactory tubercle. In untreated rats, somatostatin positive processes formed terminal plexuses in the medial septal nucleus and along an area close to the ventricular wall of the lateral ceptal nucleus. Other septal nuclei, such as the diagonal band of Broca contained a sparse innervation by somatostatin positive fibers. In contrast, the nucleus accumbens olfactory tubercle, and the substantia innominata contained a rich innervation by somatostatin positive axons and terminals. Within these structures the density of SOM positive processes show great variations with patches of densely packed terminals separated by areas of sparser or no innervation. The neurotensin positive terminals were situated predominantly within the intermediate part of the lateral septum and the medial septal nucleus. Both of these regions contained numerous pericellular baskets of neurotensin positive terminals around septal neurons. In addition to the septal innervation, several of the basal forebrain structures were rich in neurotensin positive processes with the densest innervation found in the nucleus accumbens and substantia innominata. Like the SOM-immunoreactivity distinct islands of dense neurotensin innervation separated by less or no innervation occur throughout the basal forebrain. Taken together, these findings suggest that somatostatin and neurotensin occur in separate neuronal populations and that each may influence important physiological functions within the individual septal nuclei.
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  • 6
    ISSN: 1432-0568
    Keywords: Terminal degeneration ; Dorsal rhizotomy ; Glomeruli ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After cervical dorsal rhizotomy, small dark central terminals (CI) of glomeruli underwent electron dense changes at 8 h and were all degenerated at 36 h; their number persisted, though slightly diminished, up to 15 days, glial engulfment being negligible. Light large central terminals without neurofilaments (CIIa) showed electron-lucent or electron-dense degeneration from 14 to 36 h, while those with neurofilaments (CIIb) exhibited increased neurofilamentous areas, with depletion and presynaptic concentration of synaptic vesicles as in the electron-lucent change, at the 8–36 h postrhizotomy periods. Both CII-varieties were all degenerated at 36 h and became electron dense at 48 h; glial phagocytosis was intense and no terminals were present after 4 days. It is concluded that in the rat the 3 types of central glomerular terminals are primary axons, and that each type undergoes a different pattern of degeneration which points to a separate primary afferent origin. Numerous nonglomerular axodendritic endings began showing electron-dense degeneration at 8 h which rapidly masked their normal structure, although most appeared to contain round agranular vesicles, and some of them dense-cored vesicles (in lamina I). A few endings exhibited electronlucent degeneration. Labeling methods seem preferable for studying the primary origin of nonglomerular terminals, due to the difficulty in recognizing the normal predegenerative structure of these profiles.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 170 (1984), S. 217-222 
    ISSN: 1432-0568
    Keywords: Juxtaglomerular apparatus ; Extraglomerular mesangial cell field ; Structure-function correlation ; Resetting of tubuloglomerular feedback ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extraglomerular mesangial cell field was studied by morphometric techniques in volume expanded and volume depleted rats. The volume density of the extraglomerular mesangial interstitium was found to be significantly different between the two conditions, 16.9±3.7% in volume depletion and 29.0±4.1% in volume expansion. No difference in the volume density of the peritubular interstitium could be detected under the same conditions. These findings are interpreted as indicating a specific sensitivity of the extraglomerular mesangial interstitium to changes in body fluid content, a phenomenon which may play a role in the mechanism of resetting the tubulo-glomerular feedback control.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 170 (1984), S. 117-121 
    ISSN: 1432-0568
    Keywords: Sexual dimorphism ; Serotonin fibers ; Lumbar cord ; Cremaster ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sexual dimorphism in the topographical organization of immunoreactive serotonergic fibers has been shown for the first time in the anterior column of the rat lumbar cord. A characteristic preferential arrangement of serotonergic fibers on the small cell column composed of anterior horn motoneurons, which have been proved to send their axons to the cremaster muscle, was demonstrated at the lumbar segments (L1–L2) of male rats, using the immunoperoxidase technique with antiserum against serotonin. A similar finding was also observed in female rats, but was less prominent than in males. Comparative analysis of the cell numbers and the size of neuronal somata of the aforementioned nucleus, done using retrograde transport of fluorescent dye (DAPI) via axonal fibers coursing down the genitofemoral nerve to the cremaster muscle, gave significantly larger values in males. The sexual difference in the serotonergic innervation pattern was, in consequence, surmised to be caused by the cytoarchitectonic contrast ascertained in the lumbar anterior column. Furthermore, there may be a striated muscle endowed with some active functions homologous to those of the male cremaster muscle in the female rat.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 64 (1984), S. 139-147 
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Cell death ; Endoplasmic reticulum ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An unusual, slowly progressing neuronal damage has been reported to occur in the gerbil hippocampus following ischemia (Kirino 1982). Delayed neuronal death following ischemia has also been noticed in the rat four-vessel occlusion model (Pulsinelli et al. 1982). By light microscopy this slow neuronal injury in the rat was not different from the previously known neuronal ischemic cell change. This report lead us to the question as to whether neurons in the rat hippocampus are damaged rapidly following an initial latent period or deteriorate slowly and progressively until they display overt changes. To clarify this point, observation was done on the hippocampal CA1 sector of the rat following ischemia. Rats were subjected to four-vessel occlusion, and those which developed ischemic symptoms were perfusion-fixed. Although the change appeared very slowly and lacked microvacuolation of the cytoplasm, neuronal alteration was practically not different from classical ischemic cell change. By electron microscopy, however, the change was detectable when the neurons still appeared intact by light microscopy. An increase in the membranous organelles and deposition of dark substances were the initial manifestations. It seemed that the CA1 neurons deteriorated very slowly and progressively, and that they retained partial viability in the initial phase of the change. In spite of the difference in light-microscopic findings, the mechanisms underlying delayed neuronal death in the rat and gerbil hippocampus seemed to be identical.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 65 (1984), S. 77-84 
    ISSN: 1432-0533
    Keywords: 2,4-dithiobiuret ; Rat ; Motor end plate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Daily dosing with 1–3 mg/kg dithiobiuret for 4–5 days causes progressive, generalised muscle weakness which is fatal in about 50% of cases on day 4 or 5. Survivors recover mobility by day 7 and appear normal, although still weak. Striking changes in the motor nerves and motor end plates can be observed before and during the development of this weakness, using the zinc iodide-osmium staining technique. The terminal internodes of intramuscular axons become densely stained: later this may extend back into the main intramuscular (i.m.) nerves, and is often followed by axonal degeneration. Many motor end plates lose their branching form and become globular, and profuse terminal sprouting develops before any nerve degeneration appears. Following axonal degeneration, collateral sprouting becomes prominent, and, within four weeks of beginning the dose regime, restores the normal appearance of the innervation. This pattern of response was observed clearly in the whole mounts of the sternocostalis muscle: similar but less marked changes occurred in the lumbrical muscles, while in the soleus and tibialis anterior muscles, loss of end plates seemed to be a more common response. Despite marked differences in the severity of the functional disability, the i.m. changes were similar in juvenile and adult rats. These changes are related to previous electrophysiological findings on the possible mechanism of action of dithiobiuret.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 64 (1984), S. 319-332 
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Selective vulnerability ; Neuronal necrosis ; Cell death ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The density and distribution of brain damage after 2–10 min of cerebral ischemia was studied in the rat. Ischemia was produced by a combination of carotid clamping and hypotension, followed by 1 week recovery. The brains were perfusion-fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained with acid fuchsin/cresyl violet. The number of necrotic neurons in the cerebral cortex, hippocampus, and caudate nucleus was assessed by direct visual counting. Somewhat unexpectedly, mild brain damage was observed in some animals already after 2 min, and more consistently after 4 min of ischemia. This damage affected CA4 and CA1 pyramids in the hippocampus, and neurons in the subiculum. Necrosis of neocortical cells began to appear after 4 min and CA3 hippocampal damage after 6 min of ischemia, while neurons in the caudoputamen were affected first after 8–10 min. Selective neuronal necrosis of the cerebral cortex worsened into infarction after higher doses of insult. Damage was worst over the superolateral convexity of the hemisphere, in the middle laminae of the cerebral cortex. The caudate nucleus showed geographically demarcated zones of selective neuronal necrosis, damage to neurons in the dorsolateral portion showing an all-or-none pattern. Other structures involved included the amygdaloid, the thalamic reticular nucleus, the septal nuclei, the pars reticularis of the substantia nigra, and the cerebellar vermis.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 62 (1984), S. 276-283 
    ISSN: 1432-0533
    Keywords: Rat ; Brain ; Lead intoxication ; Protein deprivation ; Growth and development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Most studies on lead toxicity in the suckling rat have been performed with doses leading to growth retardation. In a previous paper (Sundström et al. 1983), the effects of different lead doses on normal suckling rats were described. The dose of 10 mg/kg body weight daily given on days 1–15 pp produced minute hemorrhagic lesions on day 15 in the cerebellum, whereas rats given 5 mg/kg body weight daily lacked microscopically discernible pathologic changes in the brain. None of these groups exhibited growth retardation. To further elucidate the association between lead encephalopathy and malnutrition, lead was administered to protein-deprived suckling rats. Protein deprivation was achieved by a diet with 50% reduction of protein content. The móthers of the pups were fed this diet from 2 weeks before conception throughout the experiment. Experimental animals were injected i.p. with 5 mg or 10 mg lead nitrate/kg b.wt. daily. Littermates, injected with vehicle without lead nitrate served as controls. Protein-deprived rats without either treatment were “external” controls. Animals were killed at 10, 15, and 20 days age for determination of lead content in blood and brain and for light-microscopic examination. The protein-deprived rats given 10 mg/kg b.wt. daily were growth-retarded as compared to unexposed protein-deprived rats. The mortality was almost 100% at 15–20 days pp. At 15 days, the cerebellum of these rats showed abundant hemorrhages, and the cerebrum was also hemorrhagically discolored. Protein-deprived rats given 5 mg/kg b.wt. daily did not differ significantly from unexposed protein-deprived rats with regard to body weight gain. They presented a mortality of about 20% on days 15–20. At 15 days, cerebellar hemorrhages were a regular finding, though not as devastating as in the animals given 10 mg lead nitrate/kg b.wt. daily. The results imply an increased vulnerability to lead in protein-deprived rats as compared to normal rats. The severe encephalopathy in protein-deprived rats was associated with higher blood lead levels than in normal rats exposed to an equivalent lead burden.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 63 (1984), S. 57-65 
    ISSN: 1432-0533
    Keywords: Fetal alcohol syndrome ; Rat ; Cerebellum ; Purkinje cells ; Synaptic maturation ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetal alcohol syndrome was produced in rats by feeding an ethanol-enriched, vitamine-supplemented liquid diet over a period of 4 weeks before mating and throughout pregnancy. The amount of ethanol was equivalent to 38–40% of the daily calories; control animals were fed an isocaloric amount of sucrose. The offspring of experimental animals displayed a diminished birth weight. In contrast to previous experiments, the ethanol diet was also administered during the lactating period. On postnatal day 7, experimental animals and controls were killed by perfusion and the cerebella prepared for electron microscopy. Morphometric analysis showed a reduced number of Purkinje cells. On day 12, Purkinje cells of experimental animals displayed ultrastructurally fewer organelles. Furthermore, a delayed synaptogenesis in the molecular layer was demonstrated with osmiumzinc iodide and ethanolic phosphotungstic acid showing an immature appearance of the presynaptic grid and weaker stained synaptic cleft material. The following discussion deals with possible mechanisms underlying these alcohol-induced alterations of cerebellar synaptogenesis.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 64 (1984), S. 192-202 
    ISSN: 1432-0533
    Keywords: Astrocytoma ; Blood-brain barrier ; HVEM ; Transendothelial channels ; Protein tracer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain tumors, benign and malignant, are characteristically more permeable to various types of tracer molecules than the neuropil in which they are embedded. Impermeability of brain neuropil capillaries is imparted by the blood-brain barrier, the anatomic basis of which is the network of interendothelial zonulae occludentes that seal capillary endothelial cells. To explore both the vascular elements of brain neoplasms and the route of tracer extravasation from them, as well as the possible effects of brain tumors on the permeability of peritumoral neuropil capillaries, brain tumors were induced in newborn Wistar rats by intracerebral (i.c.) injection of C-6 astrocytoma cells. The protein tracer horseradish peroxidase (HRP) was injected systemically into both normal and tumorbearing rats to mark the pathway along which it flowed into the tumor parenchyma tissue spaces, and to signal any concomitant tracer loss from the tumor extracellular compartment or peritumoral brain capillaries, into the neuropil extracellular milieu. Electron-microscopic examination on thin plastic sections of tumor and peritumoral neuropil revealed massive extravasation of tracer into the tumor tissue spaces, but none was seen outside of the capillaries in the surrounding brain neuropil. Zonulae occludentes of both tumor capillary endothelium and brain capillary endothelium were devoid of tracer and judged tight (sealed). Tracer was seen in pinocytotic vesicles in the highly attenuated endothelium of tumor capillaries and also in cytoplasmic vesicles within the tumor cells. The peritumoral and contralateral neuropil capillary endothelium exhibited reaction product-filled pinocytotic vesicles and vesiculo-tubular conduits. Often, one end of a HRP-filled vesiculo-tubular channel appeared continuous with either the luminal or abluminal plasmalemma. High-voltage electron microscopy of these conduits often showed them to be continuous with both luminal and abluminal surfaces of the endothelium, thus forming a continuum across the capillary wall. In addition, these transendothelial channels, clearly constituted as chains of fused vesicles, were often seen in close proximity to, or fused with, dense bodies in the endothelial cytoplasm. In spite of the presence of HRP-filled structures in the peritumoral neuropil capillary endothelium of tumor-bearing rats, no evidence of tracer extravasation from these vessels was apparent. These results suggest that although peritumoral and contralateral neuropil capillaries possess the machinery for extravasation of tracer, likely as a response to the presence of the neoplasm, tracer is not lost but, instead, is degraded by endothelial enzymes. The extensive flooding of the tumor extracellular compartment with tracer may be achieved by transport of HRP across the very thin walls of tumor capillaries by single cytoplasmic vesicles which structurally and functionally play the role of transendothelial channels. Based on the results of this study, it is unlikely that molecules delivered systemically to treat brain neoplasms, will leak into the peritumor or contralateral neuropil, either from their own capillaries, or from the extracellular compartment of the tumor parenchyma.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 56 (1984), S. 87-91 
    ISSN: 1432-0738
    Keywords: Dimethylformamide ; N-Hydroxymethyl-N-methylformamide ; N-Methylformamide ; Metabolism ; Toxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After in vivo administration of dimethylformamide (DMF) to male rats, about 50% of the dose is excreted in urine as N-hydroxymethyl-N-methylformamide (DMF-OH) and about 4% as N-methylformamide (NMF). NMF is not a product of DMF-OH biotransformation but is directly formed from DMF. Comparison of the acute toxicity of DMF, DMF-OH and NMF shows that NMF is more toxic than DMF-OH, which is itself more toxic than DMF. This study explains the different toxicity profile of DMF and NMF which until recently was believed to represent the main metabolite of DMF.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 56 (1984), S. 109-112 
    ISSN: 1432-0738
    Keywords: 2,4,5-Tribromoimidazole ; Rat ; Neuronal necrosis ; Uncoupling of oxidative phosphorylation ; Ataxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4,5-tribromoimidazole and its 1-n-butylcarboxylate and 1-dimethylcarbamoyl derivatives, when administered to rats, induced poisoning typical of uncouplers of oxidative phosphorylation. At 48 h rats surviving a single toxic dose of 20–60 mg/kg developed permanent incoordination of the hindlimbs in the absence of brain oedema. Neuropathologic examination of brain and spinal cord from perfused fixed rats at 24 h revealed neuronal necrosis and chromatolysis in the vestibular nucleus, the outer parietal neocortex and red nucleus. Chromatolysis and necrosis in these areas had increased at 72–96 h and were also observed in the deeper layers of the neocortex, the medial entorhinal cortex, the reticular formation, the grey matter of the spinal cord extending into the ventral horns, the dorsal, and ventral cochlear nuclei and the deep cerebellar nuclei, in decreasing order of severity. Neuronal necrosis was accompanied by an increased glial response, including neuronophagia and at 16 days with astroglial hypertrophy and hyperplasia.
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  • 17
    ISSN: 1432-0738
    Keywords: Methyl mercury ; Toxicokinetics ; Differential toxicity ; Japanese quail ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Distribution of a single oral dose of methyl mercury (10 mg Hg/kg body weight) was followed from 90 min up to 120 h in plasma, erythrocytes, and brain of Japanese quails and rats. Significantly higher Hg concentrations were observed in plasma and brain of quails and red blood cells of rats. Blood/brain ratio decreased in quails from 6 to 2 at 24 h and 120 h respectively, whereas it increased in rats. Erythrocyte/plasma ratio in quails was about three times lower and averaged 54. The differences in Hg distribution were accompanied by a more than 3-fold higher acute toxicity in quails under adequate experimental conditions.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 56 (1984), S. 117-122 
    ISSN: 1432-0738
    Keywords: Rat ; Retinoids ; Bone alterations ; Adverse effects ; Arotinoid ethylsulfone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Repeated ingestion of high doses of retinoids cause the so-called hypervitaminosis A syndrome. In rats the main symptoms are weight loss, alopecia, erythema, desquamation of the skin, and alterations of the skeletal system, including bone fractures. In the present study, three retinoids (Ro 15-1570, arotinoid ethylsulfone, 6 mg/kg; retinoic acid, 100 mg/kg and etretinate, 50 mg/kg) were administered orally to rats for 1 and 2 weeks, respectively, to six male and six female rats/group. All the above changes were induced by all three retinoids, with the exception that the arotinoid ethylsulfone Ro 15-1570 did not cause bone alterations. The absence of toxic effects on the bones by Ro 15-1570 was confirmed by X-ray-film examinations, densitometry of the X-rayed femora and tibiae, examination of the thickness of the femoral and tibial compacta in histological slides plus the determination of the femoral ash weight and its main inorganic constituents (calcium, magnesium, sodium, and potassium). The present demonstration that the arotinoid ethylsulfone Ro 15-1570 was devoid of bone toxicity constitutes major progress in the pharmacologic development of retinoids with a better balance between therapeutic and adverse effects.
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  • 19
    ISSN: 1432-0738
    Keywords: 203Hg ; DMPS ; Age ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of DMPS (sodium 2,3-dimercaptopropane-1-sulfonate) in reducing inorganic mercury retention was studied in 2-, 6-, and 28-week-old albino rats. 203Hg was administered IP. The chelating agent DMPS was administered by IP injection at a dose of 250 μmol/kg body weight three times, 1 day after 203Hg administration and at 24 h intervals thereafter. The whole body retention determined 1, 2, 3, and 6 days after 203Hg administration showed that DMPS decreased the body retention of mercury in all age groups, being about twice as effective in adult compared to suckling rats. The reduced effectiveness was due to the reduced efficacy of DMPS in reducing kidney retention in young animals. In other organs the effectiveness of DMPS was not age dependent. These and previous results obtained with different chelating agents and other metals indicate that age might be an important factor in chelation therapy in general.
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  • 20
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    Electronic Resource
    Springer
    Archives of toxicology 55 (1984), S. 123-126 
    ISSN: 1432-0738
    Keywords: Rat ; Intestinal cells ; Glucuronidation ; 1-Naphthol ; Glucose ; Fructose ; d-Galactosamine ; Ethanol ; Diethyl ether ; Sorbitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glucuronidation of 1-naphthol was studied in mucosal cells isolated from the rat intestine. Glucuronidation was directly dependent on the supply of extracellular carbohydrates. Basal glucuronidation (ca. 0.3 nmoles/min · mg cell protein) was increased 2- to 3-fold by adding glucose or fructose to the incubation medium. Saturation of glucuroniation was achieved by adding 0.3 mM glucose, while saturation by fructose was not reached at concentrations below 2 mM. No carbohydrate reserves able to support glucuronidation appear to be present in intestinal cells, since no difference in glucuronidation was observed between cells prepared from fasted (18 or 42 h) and control rats. Glucuronidation was decreased by adding d-galactosamine to the incubation medium, but only when extracellular glucose was present. Various chemicals which are known to inhibit glucuronidation in hepatocytes (ethanol, diethyl ether, sorbitol) did not influence the glucuronidation of 1-naphthol in isolated intestinal cells. Only when ethanol was added to mucosal cells in the absence of extracellular glucose was a small decrease in glucuronidation observed.
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  • 21
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    Archives of toxicology 55 (1984), S. 132-136 
    ISSN: 1432-0738
    Keywords: Phthalate esters ; Inhalation ; Rat ; Enzymatic activities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague Dawley rats were exposed to dibutylphthalate (DBP) by inhalation with concentrations of 0.5, 2.5, and 7.0 ppm in the air for 5 days. The concentrations were considered relevant to human exposure. No quantitative changes were observed in liver microsomal cytochrome P-450 related enzymes, but significant increase was observed in the liver microsomal metabolism of benzo(a)pyrene and n-hexane, in the 2.5 ppm and 0.5 ppm groups, respectively. Inhaled DBF decreased in a dose-dependent way the lung microsomal concentration of cytochrome P-450 by as much as 63%, which was reflected in a significant reduction of the microsomal metabolism of n-hexane and benzo(a)pyrene in the 7.0 ppm group. It is concluded that DBP in doses relevant to human air exposure influences the cytochrome P-450 enzyme system in both liver and lung, with lung as the main target organ. The observed effects in lung microsomes were similar to those earlier reported after IP administration of high doses of DBP.
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  • 22
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    Archives of toxicology 55 (1984), S. 168-172 
    ISSN: 1432-0738
    Keywords: Aluminium ; Intestinal absorption ; Methodology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aluminium (Al) intoxication in dialysis patients is held to be caused not only by Al in the dialysis fluid but also by Al from orally administered phosphate binders. Studies on Al absorption in patients and healthy individuals as well as in animals are still scarce, and do not provide sufficient data to characterize the absorption process. This paper presents a method of studying the process of Al absorption in a perfusion system of rat small intestine in vivo, in combination with a cannulation system of the portal vein for serial blood sampling. Determination of concentrations of an absorbed substance in samples of both the perfusion medium and the portal blood, collected during the perfusion period, may clarify the nature of the absorption process. Although this method appears to be useful for the study of the intestinal absorption of any substance, it was adapted for the study of the intestinal absorption of Al compounds. The usefulness of this method for studying Al absorption was demonstrated in an experiment in which Al chloride (0.5 g/l) in buffered media of pH 7.0, 7.5, and 8.0 was perfused through the rat small intestine over a period of at least 30 min. The results of this experiment indicate that a decrease in pH of the perfusion medium leads to an increase in absorption of Al in the portal blood.
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  • 23
    ISSN: 1432-0738
    Keywords: Trialkylphosphorothioates ; Rat ; Lung ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The oral administration of an LD50 dose (25 mg/kg) of O,S,S-trimethyl phosphorodithioate to rats induced immediate, cholinergic symptoms. A delayed respiratory crisis followed, 3–4 days later, involving a pronounced increase in lung weight and extensive injury to the alveolar epithelium. This compound also induced the immediate liberation of secretory granules from the Clara cells. Minor changes in the surface appearance of these cells were also observed but no signs of injury were found in any cells of the bronchiolar epithelium. The complement of secretory granules was monitored, by the morphometric analysis of ultrathin sections. Clara cells from control animals were found to contain 9.55±1.16 (SEM) granules per cell profile. The Clara cells from dosed animals were largely devoid of granules until the 3rd day after administration. Many of these agranular cells were arranged in clusters and often showed signs of mitotic division. In surviving animals the subsequent replacement of granules resulted in a large increase in the numbers present and many exhibited abnormal morphology. Over twice the normal complement of granules, 22.45±0.42 (SEM) per cell profile, was found 6 days after dosing. The complement of granules subsequently returned to normal levels and the clusters of Clara cells were resolved within 14 days of dosing.
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  • 24
    ISSN: 1432-1106
    Keywords: Parataenial nucleus ; Nucleus accumbens ; Autoradiography ; Thalamus ; Limbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study the intrastriatal distribution of afferents arising from the parataenial nucleus of the thalamus was investigated. Tritiated leucine and proline injected into the parataenial nucleus was found to densely label the entire anterior-posterior extent of the medial nucleus accumbens. The projection was for the most part limited to this striatal subregion, although some moderate labelling was found along the medial wall of the anterior caudateputamen. The terminal labelling within accumbens was characterized by a distinct patchiness. Other efferent connections of the parataenial nucleus observed in this study include the thalamic reticular nucleus, the basolateral and central nuclei of the amygdala, the septum, the medial frontal cortex, the entorhinal cortex and subiculum. This projection is distributed to the “limbic afferented” sector of striatum, and there is a nearly complete overlap between the parataenial afferents and those coming from hippocampus. The present findings suggest that the parataenial nucleus is an important thalamic link between limbic and striatal processing.
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  • 25
    ISSN: 1432-1106
    Keywords: Cat ; Rat ; Spinal tract neurons ; Retrograde HRP transport ; Procedure and evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Modifications have been made in Mesulam's method for labelling neurons by retrograde transport of horseradish peroxidase, with tetramethylbenzidine as chromogen, with the object of increasing the extent of labelling of dendrites and axons. A procedure was devised specifically for studying spinomedullary and medullospinal tract systems, involving implanting easily-made HRP-agar pellets into areas of controlled damage in particular spinal fascicles, and sealing the site of implant with cyanoacrylate glue. Lesions of other fascicles were often made to limit transport to the implanted fascicle. Fourth-order dendrites were regularly labelled over long (30 cm or more) transport distances: axons were also labelled over this whole distance, often allowing exact study of the initial course of particular axons. Controls in both cat and rat showed that the uptake of HRP under these circumstances occurred almost wholly from the region of axonal damage at the site of implant which can be characterized histologically.
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  • 26
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    Experimental brain research 55 (1984), S. 368-371 
    ISSN: 1432-1106
    Keywords: Simple spike ; Purkinje cell ; Inferior olive lesion ; Rat ; Plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In recent experiments Montarolo et al. (1982) have shown that reversible inferior olive (IO) inactivation of up to 90 s induces a marked increase of the Purkinje cell (PC) simple spike (SS) frequency which lasts as long as the disappearance of the complex spikes (CS). The present work was aimed at studying how long this SS frequency increase lasts. We recorded the electrical activity of 724 PCs from rats (Nembutal anaesthesia 20–40 mg/kg) in which the IO was destroyed by means of cryocoagulation, electrocoagulation and 3-acetylpyridine injection. The SS activity was followed up to 1 month from the lesion. The average SS frequency of the first 5 days is 52.7 (±22.6 S.D.). The difference from the control (22.6±13.7 S.D.) is highly significant (P〈 0.001; Mann-Whitney U-test). Later the SS discharge shows a gradual decrease, to reach a value (24.2±12.1 S.D.) similar to the control at the 4th week. Our results demonstrate that the increase of the SS activity, due to the IO lesion, undergoes an adaptation. The time course of such an adaptation is well correlated with the metabolic changes in the intracerebellar nuclei, following an IO permanent lesion, described by Bardin et al. (1983).
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  • 27
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    Experimental brain research 55 (1984), S. 455-461 
    ISSN: 1432-1106
    Keywords: Rat ; Pineal gland ; Pinealocyte ; Rhythms ; Circadian rhythm ; Electrical activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular single-unit recordings were made during day- and night-time in the pineal gland of urethane-anesthetized adult male Sprague-Dawley rats. All cells exhibiting spontaneous electrical activity had firing frequencies from less than 1 Hz to about 100 Hz, and their discharge patterns were characterized as regular, irregular or bursting. While most of the spontaneously active cells (n=63) showed a uniform activity level throughout the recording period (30–120 min), a group of 9 cells exhibited oscillatory rhythms with periods of 4–8 min. In addition, long-term recordings across day- and night-time from five cells revealed increasing activity during night-time in three cells, while the remaining two units showed constant activity throughout the recording time (8–20 h). Comparison of day- and night-data in general indicated an overall higher level of activity at night.
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  • 28
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    Experimental brain research 56 (1984), S. 144-148 
    ISSN: 1432-1106
    Keywords: Rat ; Parabigeminal nucleus ; Superior colliculus ; Lateral geniculate nucleus ; HRP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The retino-recipient layers of the superior colliculus project predominantly to the dorsal and ventral divisions of the ipsilateral parabigeminal nucleus, while receiving an input chiefly from the medial division of the contralateral nucleus. A variety of retrograde tracing techniques was used to confirm that there is a projection from the medial division of the parabigeminal nucleus to the contralateral dorsal lateral geniculate nucleus in normal adult hooded rats. Some parabigeminal cells branch to supply both dorsal lateral geniculate nucleus and retino-recipient layers of the superior colliculus.
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  • 29
    ISSN: 1432-1106
    Keywords: Lateral ; Interposed nuclei ; Ipsilateral descending B.C. ; Lateral parvocellular reticular formation ; Trigeminal complex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution, organization and origin of the ipsilateral descending limb of the Brachium Conjunctivum (B.C.), have been studied in the rat by using anterograde and retrograde tracing techniques. After injections of tritiated leucine/proline into the lateral cerebellar nucleus, covering both its medial part, corresponding to the dorsolateral hump (DLH) of Goodman et al. (1963) and its lateral part, (designated here as the lateral dentate, LD), and the neighboring interposed nucleus (NI), emerging fibres are numerous and leave laterally from the B.C. On the contrary, injections restricted to LD reveal very few such fibers. Within the lateral parvocellular reticular formation (LPRF) terminal labelling is heavy, and moderate to sparse within the adjacent trigeminal complex. Rostro-caudally, silver grain accumulation within the LPRF extends from the level of the motor trigeminal nucleus (VM) to the pyramidal decussation, exhibiting a cephalocaudal decrease of grain density. Within the trigeminal complex, labelling occurs in the caudal VM, the dorsal portion of the principal sensory nucleus, and within and around the trigeminal spinalis oralis. In addition, the area surrounding the VM (in part corresponding to the supratrigeminal region of Lorente de Nó 1922, 1933) is moderately labelled. After injections of HRP into various levels of the ipsilateral descending B.C.'s projection field, retrogradely labelled cells are numerous within the DLH. A slightly lesser amount of labelled cells are found in the lateral half of the NI, primarily concerning the nucleus interpositus posterior. Within the LD, only a few labelled cells are observed: these are mainly restricted to the dorsal portion at rostral levels of the nucleus. The results obtained by both the anterograde and retrograde studies suggest an absence of a topographic organization within this descending B.C. component. The possible functional meaning of these results is discussed.
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  • 30
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    Experimental brain research 56 (1984), S. 502-508 
    ISSN: 1432-1106
    Keywords: Visual system ; Retinopetal cells ; Lateral mesencephalic tegmentum ; Retrograde tracing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The centrifugal innervation of the retina was reinvestigated in albino and pigmented rats with intraocular injections of horseradish peroxidase (HRP), radioactive wheat germ agglutinin (WGA) and proline. No labeled cells were found in the brains injected with HRP and proline, except some eye muscle motoneurons in one case apparently involving orbital contamination from the injection. In the cases injected with WGA and having a survival time of at least two days cells were labeled in the lateral mesencephalic tegmentum, ventral to the parabigeminal nucleus and in the periaqueductal gray. Both these findings are most likely due to transneuronal anterograde-retrograde transport of the tracer through the superior colliculus. The results yielded no compelling evidence for the existence of a direct retinopetal pathway in the rat, which is in contrast to a recently claimed retinal projection originating from the pretectum. Special attention was paid to the labeling in the lateral mesencephalic tegmentum, an area giving rise to retinal projections in various submammalian species. This finding is discussed with regard to the possibility that also in the rat the lateral tegmentum exerts an early influence on visual input, but at the “higher” collicular level and not at the “original” retinal one.
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  • 31
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    Experimental brain research 53 (1984), S. 341-348 
    ISSN: 1432-1106
    Keywords: Supraoptic nucleus ; Nucleus accumbens ; Septum ; Vasopressin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synaptic inputs from the nucleus accumbens (ACB) to neurosecretory cells of the supraoptic nucleus (SON) were studied in the rat. One hundred and twenty SON neurones responded antidromically to pituitary stalk stimulation and were identified as neurosecretory cells. Sixty-three of these cells were identified as vasopressin-secreting cells and 45 as oxytocin-secreting cells by their spontaneous firing patterns. About one half of the vasopressin-cells and two thirds of the oxytocin-cells were responsive to stimulation of the basal forebrain including the ACB. More vasopressin-cells were excited than were inhibited, and oxytocin-cells were mainly inhibited. Depth profile of effective stimulation sites in the basal forebrain revealed that ACB stimulation selectively produced the responses. Most of those SON neurones responsive to ACB stimulation also responded to septal stimulation. A positive correlation was observed between responses to ACB and septal stimulation in each unit. After septal lesion, the number of SON neurones which were responsive to ACB stimulation was significantly decreased. In two rats, a single SON unit was tested for ACB stimulation both before and after septal lesion, and the previously observed synaptic inputs were not seen after the lesion. Fifty septal neurones projecting to the area including the SON were antidromically identified after SON stimulation. About one half of these neurones were excited by ACB stimulation. These results demonstrate the existence of a neural pathway from the ACB to the SON and suggest that the pathway is mediated by septal neurones.
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  • 32
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    Experimental brain research 53 (1984), S. 374-383 
    ISSN: 1432-1106
    Keywords: Visual cortex ; Visual field properties ; Rat ; Vision
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Response properties of neurons in the visual cortex, area 17, of Long Evans pigmented rats were investigated quantitatively with computer-controlled stimuli. Ninety percent of the cells recorded (296/327) were responsive to visual stimulation. The majority (95%, 281/296) responded to moving images and were classified as complex (44%), simple (27%), hypercomplex (13%) and non-oriented (16%) according to criteria previously established for cortical cells in the cat and monkey. The remaining 5% of the neurons responded only to stationary stimuli flashed on-off in their receptive field. Results of this study indicate that neurons of the rat visual cortex have properties similar to those of cells in the striate cortex of more ‘visual’ mammals.
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  • 33
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    Experimental brain research 55 (1984), S. 515-522 
    ISSN: 1432-1106
    Keywords: Rat ; Serotonin ; Immunocytochemistry ; Trigeminal nuclear complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of serotonin immunoreactive (5-HT-IR) fibers in the trigeminal nuclear complex of the rat was mapped. In the sensory nuclei, innervation appeared to be dense in areas primarily related to nociceptive afferent activity, and sparse in areas primarily related to nonnociceptive afferent activity. Specifically, the marginal and gelatinosa layers of the spinal subnucleus caudalis contained many 5-HT-IR fibers while few labeled fibers were seen in the magnocellular portion of subnucleus caudalis or in the principal sensory nucleus. The spinal subnuclei oralis and interpolaris were sparsely innervated except for a few areas which contained more 5-HT-IR fibers. The motor nucleus contained as many immunoreactive fibers as the subnucleus caudalis, although fibers in the motor nucleus were thicker and varicosities more irregularly spaced than in caudalis.
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  • 34
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    Experimental brain research 55 (1984), S. 553-561 
    ISSN: 1432-1106
    Keywords: Thalamus ; Electrophysiology ; Iontophoresis ; Acetylcholine ; Choline acetyltransferase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several lines of evidence suggest a role for ACh in the mediation of cerebello-thalamic transmission. The physiological, pharmacological and biochemical experiments described were designed to test this hypothesis for the rat cerebello-thalamic pathway. Unilateral electrolytic lesions of the superior cerebellar peduncle resulted in modest falls of CAT from both ventromedial thalamic nuclei (contralateral 35%, ipsilateral 15%). Iontophoretic application of ACh to relay cells evokes three types of response (i) excitation (ii) inhibition (iii) polyphasic combinations of (i) and (ii). The type of response evoked was directly related to the firing pattern of the cell. Thus, for example, excitatory responses were never recorded during high-frequency bursting but were easily evoked following a switch to tonic, single-spike activity. All responses to ACh and synaptic responses to cerebellar stimulation were sensitive to muscarinic but not to nicotinic cholinergic antagonists. The nicotinic antagonist mecamylamine was a potent blocker of excitant amino acid responses but had no effect on cerebellarevoked synaptic responses. Cholinergic and anticholinergic agents had a profound action on relay cell firing pattern. ACh promoted single-spike activity whereas atropine promoted high-frequency bursting. The actions of ACh are discussed with reference to recently discovered voltage-sensitive ionic conductances. Because of the modulatory action of ACh on relay cell firing pattern and excitability no firm conclusion can be reached concerning the hypothesis under test here. We tentatively suggest a dual role for ACh as both neurotransmitter and neuromodulator.
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  • 35
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    Experimental brain research 55 (1984), S. 535-552 
    ISSN: 1432-1106
    Keywords: Thalamus ; Cerebellum ; Basal ganglia ; Electrophysiology ; Rat ; Firing patterns ; Transmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the basis of antidromic stimulation we have identified two distinct neuronal populations in the rat ventromedial thalamic nucleus. The largest population (96%) are thalamo-cortical relay cells which project via the internal capsule to the cerebral cortex. The smaller population of cells (4%) project caudally to the reticular formation and superior colliculus. These two cell types could be distinguished further on the basis of their patterns of spontaneous discharge. Relay cells fluctuate between two activity patterns (i) a rhythmic pattern characterized by periods of high-frequency bursting, and (ii) a more tonic discharge pattern of single spikes. The caudally projecting cells had a characteristic fast, regular type of spontaneous firing. Brachium conjunctivum stimulation evokes two distinct responses in thalamic relay cells, (i) a short-latency single spike, (ii) a longer latency, rhythmic response of 2–3 spikes. Both excitatory responses are followed by a period of cell quiescence. The type of response is dependent upon the cell's firing pattern. The short-latency response occurs during tonic, single-spike activity whilst the longer latency response occurs during highfrequency bursting activity. The short-latency response can be altered to the long latency response by increasing the level of anaesthesia or by applying a conditioning shock to known inhibitory pathways. Conversely the long latency response can be altered to the short-latency response by decreasing anaesthesia or by stimulation of the reticular formation. It is argued that both response types are evoked monosynaptically by activation of the same cerebello-thalamic fibres but that different ionic conductances which are active at different levels of membrane polarization are responsible for the two response patterns. Efficient time-locked cerebellothalamo-cortical transmission occurs only during tonic single-spike activity, when cerebellar stimulation evokes a short-latency response. Such transmission is allowed or disallowed by the fine balance between converging excitatory and inhibitory afferents. In addition to a monosynaptic excitatory input from the cerebellar nuclei, relay cells received converging synaptic inputs from the substantia nigra, cerebral cortex, reticular formation and superior colliculus. Due to the anatomical arrangement in the rat it proved impossible to assess the role of the pallidum. The population of caudally projecting cells also received several converging synaptic inputs, but unlike those influencing relay cells, these inputs were all excitatory. We have obtained no clear physiological evidence for the occurrence of local interneurones within the ventromedial nucleus. However, a powerful recurrent inhibitory circuit is activated following antidromic activation of relay cells. The interneurones responsible for this inhibition appear to lie in the thalamic nucleus reticularis.
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  • 36
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    Experimental brain research 55 (1984), S. 579-585 
    ISSN: 1432-1106
    Keywords: Septo-Hippocampal projections ; Hippocampal afferents ; Cholinergic projections ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a series of experiments in which the known projections of the septal complex to the hippocampal formation have been transected, we have used both anterograde and retrograde tracing techniques in an attempt to demonstrate a ventral septo-hippocampal pathway. In cases where transections of the fimbria, dorsal fornix and supracallosal stria were complete, injections of the retrograde tracers wheat germ agglutinin-conjugated horseradish peroxidase or Fast blue, resulted in labeled cells in the ipsilateral septal complex, primarily in the nucleus of the diagonal band. The number of cells labeled in these experiments was approximately 5–10% of that seen in experiments in animals with intact dorsal pathways who had received similar injections. The presence of a ventral pathway was confirmed in anterograde labeling experiments in which injections of 3H-amino acids were made into the septal complex. The autoradiogfaphs demonstrated that the projection terminates most heavily in the entorhinal cortex and to a lesser extent in the ventral subicular complex; there may be an additional minor projection to the temporal half of the hippocampus and dentate gyrus. Finally, using double labeling procedures, we were able to demonstrate that at least a portion of the cell population that gives rise to the ventral pathway demonstrates choline acetyltransferase immunoreactivity and is presumably cholinergic.
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  • 37
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    Experimental brain research 57 (1984), S. 107-117 
    ISSN: 1432-1106
    Keywords: Development ; Rat ; Optic nerve ; Cell death ; Myelination ; Eye removal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the albino rat, the number of optic axons increases from 400 on embryonic day 15 to reach a peak of 240000 at birth, before declining to adult numbers (100000) by postnatal day 5. Throughout the period of loss of axons there are few signs of degeneration in the optic nerve, which does not change its diameter: the decrease in density of axons is matched by an increase in the cross-sectional area of individual axons. Myelination of the initially non-myelinated axons starts on day 5, when axonal numbers stabilize. Following neonatal removal of one eye, fewer axons than normal are present in the contralateral optic nerve up to day 5. The axons removed by enucleation may be retino-retinal axons, representing up to 40% of the 83000 fibres lost between postnatal days 2 and 5. There is no increase in the numbers of optic axons in the remaining nerve in adult animals; this appears to be due to the small absolute numbers of ipsilateral axons saved by enucleation. After enucleation, axons remain clear and undergo a “watery” degeneration after initially swelling, and the removal of degenerative products is accomplished within four days.
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  • 38
    ISSN: 1432-1106
    Keywords: Harmaline tremor ; Cerebellum ; Inferior olive ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Purkinje cells were recorded extracellularly and mapped in the cerebellar cortex of the rat under tremogenic doses of harmaline. Four différent types of responses were encountered, of which two were considered as being responsible for the harmaline tremor. The latter had a regular firing pattern of complex spikes at 5 to 10 Hz and were mostly found in the vermis. Their number decreased in the more lateral region of the cerebellar cortex until they eventually disappeared. Horseradish peroxidase was injected into all the areas of the cerebellar cortex containing Purkinje cells with harmaline-induced activity. Labeled neurons were in all cases traced to the medial accessory olive. The metabolic activity of the inferior olive under harmaline was measured with 2-deoxyglucose. Increased labeling was only found in the medial accessory olive. Such an increase was demonstrated as being due to a direct effect of the drug on the inferior olivary neurons, indicating that the medial accessory olive is responsible for the harmaline tremor in the rat. Our results point out that, in the rat, there is an inverse relationship between serotoninergic innervation of a region in the inferior olivary nucleus and that with harmaline sensitivity, therefore a serotoninergic mechanism hypothesis for the harmaline tremor needs further investigation.
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  • 39
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    Experimental brain research 54 (1984), S. 337-348 
    ISSN: 1432-1106
    Keywords: Optokinetic pathways ; Pretectum ; Prepositus hypoglossi complex ; N. reticularis tegmenti pontis ; Vestibular nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1) Intra-and extracellular responses of neurons in the pretectum (Pt), the nucleus reticularis tegmenti pontis (NRTP), the prepositus hypoglossal complex (NPH) and the vestibular nuclei (VN) were recorded during orthodromic/antidromic stimulation of their afferent/efferent fibers. 2) In the Pt, many neurons were excited by stimulation of the contralateral optic nerve (ONc). Comparison of the latencies of evoked presynaptic action potentials and EPSPs yielded a time difference corresponding to one synaptic delay. Forty five per cent of these monosynaptically driven neurons were also excited antidromically from the ipsilateral NRTP. 3) In the NRTP, ONc and Pt stimulations evoked disynaptic and monosynaptic EPSPs, respectively. Thirty six per cent of NRTP neurons orthodromically driven from ONc and/or ipsilateral Pt stimulation were also antidromically invaded from either the contralateral (67%) or the ipsilateral (33%) flocculus but never from both. 4) In the NPH, both ipsilateral Pt and NRTP stimulations excited type II neurons monosynaptically. In addition, EPSPs evoked by Pt stimulation could be mediated to the NPH via a disynaptic route involving the NRTP. 5) In the VN, type II neurons were excited by ipsilateral Pt stimulation. When comparing the latencies of action potentials and EPSPs evoked by Pt stimulation in the NPH and in VN type II neurons respectively, a short, possibly monosynaptic connection, may be postulated between the NPH and the VN. 6) Our results suggest that vestibular neurons may be optokinetically driven from the contralateral eye both via Pt-NPH connections and Pt-NRTP-NPH paths. They also confirm the existence of a transcerebellar route from the Pt via the NRTP to the ipsior contralateral flocculi.
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  • 40
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    Experimental brain research 54 (1984), S. 437-445 
    ISSN: 1432-1106
    Keywords: Rat ; Spinal motoneurones ; Recurrent discharge ; Electrical synapse ; In vitro study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The excitatory interaction between spinal motoneurones was investigated by means of electromyogram (EMG) recordings from hindlimb muscles as well as intracellular ones from their innervating motoneurones in the isolated preparation of immature rats. Stimulation of the muscle nerve to biceps femoris or medial gastrocnemius or of the L5 ventral root evoked early and late EMG responses in the muscle of the preparations with the dorsal roots cut. The early response was produced directly by volleys in the motor nerve. The late response was of spinal origin, since it disappeared after the severance of the ventral root. The thresholds and the conduction velocities of nerve fibres, which conducted the centripetal impulse causing the late response, were compatible with those of motor nerve fibres. The amplitude of the late response was 5–10% of that of the maximum early EMG response. Intracellular recordings from spinal motoneurones revealed that stimulation of the ventral root elicited the double discharge composed of antidromic and delayed spike potentials. The delayed spike was never evoked after the spike potential elicited directly by a short depolarizing pulse. The double discharge was observed in about 6% of the motoneurones examined. The threshold of the stimulus intensity evoking the double discharge was in the range of those of motor nerve fibres. The latencies of the delayed excitation were 7.0–9.0 ms, comparable to the intraspinal delays of the late EMG response. Stimulation of the ventral root at intensities subthreshold for antidromic activation was found to produce a small depolarizing potential in about 60% of the motoneurones examined. The amplitudes were 0.5–5.0 mV, and the onset and the peak latencies 2.0–7.0 ms and 5.0–8.0 ms, respectively. The potential was unaffected by the deficiency of calcium ions in the perfusing medium and persisted after the degeneration of the afferent fibres in the ventral root. It was thus concluded that the depolarizing potential was generated by electrical synapses between motoneurones. In a few motoneurones the electrical synaptic potential was found to elicit spike potentials. Latencies of these spikes were similar to those of the delayed excitation in motoneurones with the double discharge. The time course of changes in the excitability in these motoneurones showed that the delayed excitation, hence the late EMG response, was also caused by the electrical synaptic potential.
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  • 41
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    Experimental brain research 53 (1984), S. 223-232 
    ISSN: 1432-1106
    Keywords: Cortico-geniculate influence ; Lateral geniculate nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unitary discharges of the lateral geniculate nucleus (LGN) were analyzed in anesthetized and paralyzed rats after inactivation of visual cortical areas (VC) by cryoblockade or by depositing a cotton wick soaked in KCl (3 M). The receptive fields were mapped prior to and following the interruption of the cortico-geniculate feedback. The responsiveness of the VC was controlled by monitoring evoked potentials and the EEG. In most off-center and about half on-center cells the surround excitatory responses were markedly reduced and even totally abolished. In contrast, the center excitation remained unchanged or increased suggesting a parallel decline of the inhibitory surround. This differential influence of cortical blockade on on- or off-responses failed to appear in on-off cells whose receptive field was nonconcentrically organized. It is proposed that the VC exerts a complex influence upon geniculate physiology while the spatial center-surround relationships are under the control of the VC. The results of this investigation are comparable to those obtained in rabbits and cats.
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  • 42
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    Experimental brain research 54 (1984), S. 1-6 
    ISSN: 1432-1106
    Keywords: ACTH ; Urethane ; Corticosterone ; Rat ; Electrical stimulation ; Pituitary-adrenal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of limbic forebrain stimulation on pituitary-adrenal function was assessed by evaluating plasma corticosterone obtained prior to and following sham or electrical stimulation of urethane (1.20 g/kg) anesthetized female rats. Cortical electroencephalogram (EEG), electrocardiogram (ECG), heart rate (HR), mean arterial blood pressure (MAP), and respiration were routinely monitored. Timed blood samples (0.25 ml) were obtained from a catherized femoral artery. The HR (Bts/min), MAP (mm of Hg), and corticosterone levels (μg/dl) for 7 non-stimulated rats averaged over 6 sampling periods were 385±19, 95±6, and 70.3±5.8 respectively. In electrically or sham stimulated rats, blood samples were taken just prior to stimulation (biphasic square waves, 100 μA, 50 or 60 Hz, 1 ms, 1 s on/1 s off for 15 or 30 min) and 5, 10, 15, and 30 min after initiation of stimulation. Significant changes in plasma corticosterone levels were obtained following stimulation of hippocampal and amygdaloid areas. In contrast, no change in corticosterone concentration was observed following stimulation of cortex, corpus callosum, fornix and a variety of other CNS areas. Detailed analysis of hippocampal influence on urethane stimulated plasma corticosterone levels showed increased plasma corticosterone levels following stimulation of CA1. In contrast, stimulation of CA3, dentate (includes CA4) and the subiculum produced significant decreases in plasma corticosterone levels. No change in corticosterone levels was observed following sham stimulation. Collectively, these data indicate that consideration must be given to the possibility that differential neuroendocrine regulatory mechanisms reside within various limbic forebrain complexes and that electrical stimulation of limbic forebrain sites of urethane anesthetized rats may provide information regarding sites inhibitory to pituitary-adrenal activity.
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  • 43
    ISSN: 1432-0738
    Keywords: TCDD ; 2,3,7,8-Tetrachlorodibenzo-p-dioxin ; 3-Methylcholanthrene ; Phenobarbital ; 2,3,7,8-Tetrabromodibenzo-p-dioxin ; Toxaphene ; 5-Chloro-2-(2,4-dichlorophenoxy)phenol ; 4,5,6-Trichloro-2-(2,4-dichlorophenoxy)phenol ; Vitamin A ; Retinol ; UDP-glucuronosyltransferase ; Aryl hydrocarbon hydroxylase ; Liver ; Rat ; High pressure liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrabromodibenzo-p-dioxin (TBrDD), 5-chloro-2-(2,4-dichlorophenoxy)phenol(3-Cl-predioxin) 4,5,6-trichloro-2-(2,4-dichlorophenoxy)phenol (5-Cl-predioxin), toxaphene, 3-methylcholanthrene (3-MC) and phenobarbital (PB) on the vitamin A storage, UDP-glucuronosyltransferase (UDPGT) and aryl hydrocarbon hydroxylase (AHH) activities in the liver of Sprague-Dawley rats was investigated. Vitamin A was determined as retinol by high pressure liquid chromatography. UDPGT was measured with p-nitrophenol as an aglycone and AHH with 3,4-benzopyrene as a substrate. Both in TCDD- and toxaphene-treated animals a reduced body weight gain was recorded, but no other overt signs of toxicity were seen in this study. Both the concentration and the total amount of hepatic retinol was significantly reduced in TCDD-, 3-MC-, PB- and TBrDD-treated animals. These compounds were also those which gave the most significant enzyme induction as regards the UDPGT and AHH activities. However, the reduction of hepatic retinol caused by these compounds did not correlate with the enzyme activities studied. When compared on a molecular basis, TCDD and TBrDD were in the order of several magnitudes more potent as reducers of hepatic retinol and likewise as enzyme inducers.
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  • 44
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    Journal of cancer research and clinical oncology 108 (1984), S. 56-59 
    ISSN: 1432-1335
    Keywords: DNA methylation ; Rat ; Procarbazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cytostatic drug procarbazine has previously been shown to be a potent transplacental neurotropic carcinogen in rats. Following a single IP administration of (14C-methylprocarbazine (110 mg/kg) on day 22 of gestation, methylation products with cellular DNA were determined in fetal and maternal rat organs. The concentration of the major adduct N7-methylguanine was highest in the maternal liver (224 μmol/mol guanine). Fetal and nonhepatic maternal tissues exhibited significantly lower levels, but differed little from each other. In brain, lung, intestines, and placenta the O 6-methylguanine/N7-methylguanine ratio was close to 0.11, indicating that procarbazine, like other methylating carcinogens, initiates malignant transformation via methyldiazonium hydroxide as the ultimate reactant. Following a single dose of (14C-methyl)procarbazine to newborn animals, methylpurine values were 30–60 times lower than after prenatal administration. This suggests that DNA alkylation in nonhepatic tissues occurs by systemic distribution of a proximate carcinogen formed in the adult rat liver.
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  • 45
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    Journal of cancer research and clinical oncology 108 (1984), S. 114-120 
    ISSN: 1432-1335
    Keywords: Nasal cavities ; Rat ; DOPN
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Weekly SC administration of 2,2-dioxopropylnitosamine to 88 Sprague-Dawley rats resulted in the induction of 76 separate neoplasms in the respiratory region of the nasal cavities. No tumors of the olfactory region were found. Histologically there were 37 squamous papillomas, 17 transitional papillomas, and 22 squamous cell carcinomas. These tumors were compared with a selected group of 53 related human tumors of the nasal and paranasal cavities, consisting of 11 squamous cell papillomas, 13 transitional papillomas, and 29 squamous cell carcinomas. While the experimental squamous cell papillomas showed a striking histological resemblance with the squamous papillomas observed in man, none of the experimental transitional papillomas had evidence of the characteristics inverted pattern seen in humans: nevertheless, the experimental tumors showed signs of incomplete squamous metaplasia and preservation of intraepithelial secretory glands, features commonly seen in transitional papillomas of man. The squamous cell carcinomas of this experiment were very similar to the corresponding human tumors in morphology and sex incidence. In both species a significant number of squamous cell carcinomas were keretinizing and of a high grade of histological malignancy. In addition, 69% of the human squamous cell carcinomas occurred in the male sex, and 72% of the experimental carcinomas developed in males. This comparative study suggests that further studies investigating the significance of nitrosamines as suspected etiologic factors of nasal carcinogenesis in man may be useful.
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  • 46
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    Diabetologia 26 (1984), S. 76-80 
    ISSN: 1432-0428
    Keywords: Rat ; islets of Langerhans ; oestradiol treatment ; adrenal glands ; corticosterone treatment ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ovarian-adrenal interactions on insulin secretion during oestradiol treatment were studied in sham-operated, ovariectomized and adrenalectomized-ovariectomized female rats, the latter thus treated to suppress interference from endogenous hormones. Islets of Langerhans isolated from oestradiol or oestradiol + corticosterone treated and control rats were incubated with various glucose concentrations. Oestradiol treatment enhanced basal and glucose stimulated insulin secretion from sham-operated (+12%) or ovariectomized rats (+24%). This effect disappeared in adrenalectomized-ovariectomized rats but reappeared when adrenalectomized-ovariectomized rats were treated with oestradiol + corticosterone (+37%). A 14-day oestradiol treatment had a trophic effect on total protein content independent of adrenal presence (+14%; +15%; +31%; +23% versus respective control groups). Our data demonstrate that corticosterone is necessary for the stimulating effect of oestradiol on insulin secretion.
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  • 47
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    Diabetologia 27 (1984), S. 32-37 
    ISSN: 1432-0428
    Keywords: Rat ; kidney ; streptozotocin diabetes ; tubular lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Renal tubular lesions have been studied in streptozotocin-diabetic rats after 50 days of diabetes and compared with age-matched controls. The kidney weight increased by 67% in the diabetic animals and the length of the proximal tubules increased by 22%, but no abnormalities were found. The length of the distal tubules increased by 20% and the total increase was due to abnormal distal tubules. These abnormalities were confined to the cortex and the outer stripe of the outer medulla, but they were not seen in the inner stripe of the outer medulla. Abnormal cells were found also in the distal tubular cells of the macula densa. The total length of the collecting ducts was the same in the two groups and the cells appeared normal. The cells of the abnormal distal tubules appeared either empty or full of a PAS-positive material, digestable with α-amylase. At the electron microscope level, the cytoplasm of the cells contained glycogen-like granules, strikingly few organelles and the basal infoldings were greatly reduced. It is suggested that these tubular lesions might play a role in the development of renal functional changes in diabetes.
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  • 48
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    Naunyn-Schmiedeberg's archives of pharmacology 326 (1984), S. 248-253 
    ISSN: 1432-1912
    Keywords: Neonatal capsaicin ; Antinociceptive effects ; Adjuvant arthritis ; Substance P ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were treated with capsaicin (50 mg/kg, SC) either on the second day or on the second and third days of life. A significant attenuation of the responses to noxious stimuli was obtained in the capsaicin treated animals as measured by the hot-plate or paw pressure tests but not by the tail-flick test. Furthermore, neonatal capsaicin produced a significant reduction of response in the formalin test. Capsaicin reduced the reaction latency in rats with adjuvant arthritis as measured by the hot-plate and paw pressure tests, though capsaicin did not alter the overall time course of the response to Freund's adjuvant. Capsaicin also attenuated the weight loss or the decreased ambulatory and rearing behaviour which occurred in the control animals with adjuvant arthritis. It is suggested that neonatal treatment with capsaicin may relieve the responsiveness to longlasting nociceptive stimuli by adjuvant in rats.
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  • 49
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    Naunyn-Schmiedeberg's archives of pharmacology 327 (1984), S. 14-17 
    ISSN: 1432-1912
    Keywords: Bethanechol ; Electromyogram ; Substantia nigra pars reticulata ; Morphine ; Muscular rigidity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bethanechol chloride (5–25 μg), when injected into the substantia nigra pars reticulata (SNR) of rats, produced muscular rigidity in a dose-dependent way, and in addition, catalepsy and ipsilateral posture. The effects of bethanechol in the dose of 25 μg were prevented by coadministration of 10 μg scopolamine hydrochloride. Injections of 25 μg betanechol or 10 μg scopolamine into the reticulata only slightly affected the muscular rigiditiy produced by 15 mg/kg i.p. morphine hydrochloride. The results suggest that muscarinic cholinergic mechanisms in the substantia nigra pars reticulata, although effective by themselves, affect by expression of at least one striatal functional alteration, the muscular rigidity, in a less effective way than GABAergic or endogenous opioid mechanisms do.
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  • 50
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    Naunyn-Schmiedeberg's archives of pharmacology 326 (1984), S. 227-232 
    ISSN: 1432-1912
    Keywords: Pentobarbital ; Benzodiazepine derivatives ; Cerebellar Purkinje cell ; Interposed nucleus cell ; Discharge pattern ; Rabbit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The discharge of cerebellar neurons was investigated in the rabbit and the rat under the influence of pentobarbital, diazepam or medazepam. In the rabbit, these drugs are known to induce a rhythm ranging between 4 and 25 Hz in the red nucleus (RN) and the cerebellum (Cb). Purkinje cells (P cells) in the intermediate zone of the cerebellar cortex as well as neurons of the interposed nucleus (IPN) were found to discharge with burst patterns fully synchronized with the drug-induced RN rhythm. In contrast, P cells in the medial cerebellar zone responded to these drugs only with changes in their discharge rate. Since P cells of the intermediate longitudinal zone project to the RN mainly via the IPN, the present findings complement our previous results, indicating that the rhythmic electrical activity in the RN is initiated by the cerebellum. The three drugs had similar effects on the activity of cerebellar units in the rabbit and the rat. The investigation also shows that, in spite of the uniform morphological structure of the cerebellar cortex, P cells do not respond uniformly to a given drug: the diversity of findings published on the P cell response to barbiturates or benzodiazepine derivatives may be explained by differences in the recording sites.
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  • 51
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    Pflügers Archiv 401 (1984), S. 414-417 
    ISSN: 1432-2013
    Keywords: Brown adipose tissue ; Microspheres ; Noradrenaline ; Rat ; Regional blood flow ; Xenon clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The xenon clearance method was adapted to continuous measurement of interscapular brown adipose tissue (ISBAT) blood flow in anaesthetized rats. The ISBAT-blood partition coefficient for xenon was determined to 3.6 ml·g−1. The blood flow values obtained by Xe clearance were compared with flow values obtained concomitantly by the microsphere technique in 17 cold acclimated rats, at ISBAT blood flows between 0.1 and 6 ml·g−1·min−1. Variations in blood flows were obtained by infusion of noradrenaline at different rates. The blood flow values obtained from the xenon clearance method showed a close correlation to the blood flow values determined with microspheres.Y=0.98.X+0.15 (r=0.96,P〈0.001). The Xe clearance method has the advantages compared to the microsphere technique that it permits continuous monitoring of the blood flow and does not require the sacrifice of the animal.
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  • 52
    ISSN: 1432-2013
    Keywords: Cardiac anoxia ; Enzyme release ; Reoxygenation damage ; Mitochondrial swelling ; Contracture development ; Cell lysis ; Adult heart cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cultured adult cardiac myocytes were exposed to anoxia under substrate-free conditions and then reoxygenated. When comparing the oxygen deficient organ to the anoxic cell culture, we see that metabolic changes in the latter system proceed in a similar, yet prolonged manner, as in arrested hearts. Release of cytosolic enzymes starts with minor energetic disturbances and proceeds closely correlated to the actual ATP level. Below 2 μmol ATP/gww, an increasing number of cells becomes irreversibly damaged, above this level, 30 min reoxygenation leads to extensive recovery of the whole preparation. The results indicate that leakage of cytosolic enzymes during the early stage of anoxia is due to a gradual protein release from the individual cells and is related to reversible membrane alterations. Reoxygenation does not induce changes considered typical of the ‘oxygen paradox’. Since mechanical cell-cell interactions are absent in this model, it is suggested that aggravation of tissue damage in heart tissue reoxygenated late is mainly caused by mechanical forces.
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  • 53
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    Psychopharmacology 82 (1984), S. 181-184 
    ISSN: 1432-2072
    Keywords: Corticosterone ; Adrenal catecholamine ; Ethanol ; Withdrawal ; Naloxone ; Stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats maintained on an ethanol-liquid diet developed physical dependence after 16 days. Activation of adrenocortical function and overactivity of the sympathoadrenal system were observed during withdrawal from ethanol. The opiate antagonist naloxone prevented the adrenomedullary response, and attenuated, though not significantly, the increases in serum corticosterone induced by ethanol deprivation. These findings suggest that endogenous opioid pathways may be involved in the ethanol-withdrawal syndrome.
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  • 54
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    Psychopharmacology 82 (1984), S. 185-188 
    ISSN: 1432-2072
    Keywords: Stress ; Antinociception ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of drugs which alter dopaminergic function on footshock-induced antinociception were studied in the rat. Antinociception due to brief (30 s) footshock was inversely related to dopamine (DA). Thus, it was increased by the DA receptor antagonists pimozide and haloperidol and decreased by the specific D2 dopamine receptor agonist LY 141865, but not by the specific D1 agonist SKF 38393. Although pimozide increased the antinociceptive effect of 30-s shock, it decreased that of 30-min shock. It is suggested that DA may have physiological roles in stress-induced antinociception, and that these may differ according to the duration of stress.
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  • 55
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; Intracerebral infusion ; Dopamine ; Neurotransmitter substances ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats selected as high-activity and low-activity responders to the hyperactivity-inducing action of peripherally administered (-)N-n-propylnorapomorphine [(-)NPA] were subject to intra-accumbens infusion of dopamine, noradrenaline, serotonin, acetylcholine and GABA (0.48 μl/h, 25 μg/24 h, 13 days). Locomotor activity was measured during infusion and for a minimum of 35 days thereafter. After discontinuation of infusion the animals' responsiveness to (-)NPA was also assessed and, on the 2nd day of withdrawal, sensitivity to the hyperactivity-inducing action of acute intra-accumbens dopamine was determined. Dopamine caused a biphasic pattern of hyperactivity during infusion with peaks of responding between days 2–5 and 8–12: normal values returned after withdrawal of infusion. However, 2–3 weeks after withdrawal of intra-accumbens dopamine infusion animals showed reversed responding to (-)NPA challenge, the initial low-active animals giving a high-active response and high-active animals giving low-activity. Infusions of noradrenaline, serotonin, GABA and acetylcholine produced some increase in locomotor activity towards the termination of infusion, but no treatment could replicate the first hyperactivity peak and no treatment, after withdrawal, could reverse the responsiveness to (-)NPA of high- and low-active animals. Acute injections of dopamine into the nucleus accumbens showed that the infusion of the different neurotransmitter substances caused change within that nucleus. Nevertheless, changes in locomotor behaviour following the infusion of dopamine into the nucleus accumbens are specific for dopamine.
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  • 56
    ISSN: 1432-2072
    Keywords: Naloxone ; Methamphetamine ; Apomorphine ; Haloperidol ; Stereotypy ; Catalepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment with the opiate antagonist naloxone, at 1.25–5 mg/kg, increased the intensity of methamphetamine stereotypy, had no effect (over a range of 0.3125–5 mg/kg) on apomorphine stereotypy, and antagonized haloperidol catalepsy in rats at 1.25–5 mg/kg. It is suggested that naloxone, by blocking the opiate receptors located on the nigro-striatal and mesolimbic dopamine (DA) nerve terminals, releases the DA systems from endogenous inhibition, presumably caused by endogenous opiate systems, and thereby potentiates methamphetamine stereotypy and antagonizes haloperidol catalepsy. However, the possibility that naloxone might have affected methamphetamine stereotypy and haloperidol catalepsy by modulating the activity of the central noradrenergic and GABAergic systems, which are reported to influence dopaminergically mediated behaviours, also needs to be considered.
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  • 57
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    Psychopharmacology 82 (1984), S. 241-247 
    ISSN: 1432-2072
    Keywords: Opiates ; Morphine ; Naloxone ; Conditioned place preference ; Reward ; Reinforcement ; State-dependent learning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats, conditioned place preferences are produced by morphine and conditioned place aversions produced by naloxone. In the present studies, several issues concerning the demonstration and interpretation of place conditioning findings were examined in a two-compartment (black and white) tilt box: (1) the responses of naive rats to testing, (2) place conditioning in rats with strong unconditioned biases to one of the sides, and (3) modifications of the testing situation so that naive rats respond to the black and white sides with a minimum of initial bias. Experiments involving manipulation of the conditions of training and testing, use of pentobarbital, and use of a three-compartment test box helped to control for morphine's ability to produce state dependent learning as an explanation of its conditioned place preference. In addition, we examined previous place conditioning studies that failed to show aversive effects of naloxone. These negative findings were suggested to be due to the use or procedures insensitive to aversive stimuli and to the IP administration of naloxone. Finally, in the course of the experiments, novel data on general parameters of the place conditioning were provided. Dose-response curves for subcutaneous (SC) morphine (0.04–5.0 mg/kg) and naloxone (0.02–5.0 mg/kg) were established. Conditioned preferences were also shown to occur after at three pairings of SC drug, and they were retained for at least 1 month.
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  • 58
    ISSN: 1432-2072
    Keywords: Saccharin intake ; Pain threshold ; Diabetes ; Streptozotocin ; Morphine tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats of the LC-2-HI strain, selected for high rates of self-stimulation, were supplied with a 3 mM saccharin solution. Within 1 week they developed markedly prolonged latencies to painful stimuli on a hot-plate. In contrast, a similar effect became manifest in LC-2-LO rats only after 3 weeks. Both strains of rats were made diabetic by injection of streptozotocin. LO rats showed more polydipsia and hyperglycemia than HI rats and, when drinking saccharin solution, developed cross-tolerance to morphine within about 2 weeks. It is assumed that saccharin consumption stimulates the release of endogenous opioid peptides, probably via stimulation of gustatory sweet receptors. The opioid peptides exert a biphasic effect: initially they raise the pain threshold, but at a later stage they cause chronic crosstolerance to morphine.
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  • 59
    ISSN: 1432-2072
    Keywords: Punishment-induced suppression ; Diazepam ; Serotonin ; Dorsal raphé ; Substantia nigra ; 5,7-Dihydroxytryptamine ; Ro 15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 μg in 0.4 μl) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 μg in 0.5 μl) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10−5–10−4 M in 0.2 μl) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.
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  • 60
    ISSN: 1432-2072
    Keywords: Opiates ; Opioid peptides ; Enkephalin analogues ; β-Endorphin ; Analgesia ; Species differences ; Morphine ; d-Met2, Pro5-enkephalinamide ; Rat ; Mouse ; Opiate receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). β-Endorpin, d-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of μ- and δ-receptors in mediation of the analgesic effect induced by different types of opioids.
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