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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetic properties of the antimuscarinic drug [3H]-hexahydro-sila-difenidol in the rat (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 146-152 
    Details
    ISSN: 1432-1912
    Keywords: Pharmacokinetics ; [3H]-Hexahydro-siladifenidol ; Sila-drug ; Rat ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pharmacokinetics of tritiated hexahydrosila-difenidol ([3H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography. After i. v. administration of 2.9 mg/kg HHSiD plus [3H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5% of the radioactivity was recovered in blood after 23 s and 0.4% after 2.5 h. 64% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52% of the radioactivity was eliminated within 2.5 h, 13% by urinary and 39% by biliary excretion. Following oral administration of 8.6 mg/kg HHSiD plus [3H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i. v. injection) as well as by tissue distribution measurement the highest levels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and pancreas. Thus, after i. v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00166957
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of morphine on different aspects of social play in juvenile rats (1995)
    Springer
    Psychopharmacology 117 (1995), S. 225-231 
    Details
    ISSN: 1432-2072
    Keywords: Social play ; Opioid ; Morphine Environment ; Social isolation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify the influence of opioids on social play, the effects of morphine on playful and non-playful social behavior in juvenile rats was investigated under different conditions. Environmental variables employed were different (dim and intense) levels of illumination during testing, familiarity to the test cage, and different periods of social isolation prior to testing. Under dim light conditions, morphine markedly increased playful social behavior, such as pinning, boxing/wrestling and following/chasing, whereas non-playful social behavior such as social exploration and contact behavior was hardly affected. This effect of morphine was independent of duration of previous isolation and dose-dependent, with a maximal effect at 1.0 mg/kg. The mechanism of this effect is interpreted as an action on the rewarding aspects of play. A dose of 0.1 mg/kg of morphine abolished the initial suppression of play induced by unfamiliarity to the test cage, without influencing total levels of play. This may be an effect of morphine on the integration of sensory stimuli. Under intense light conditions, where playful behavior was completely suppressed, morphine itself hardly affected such behavior, but decreased some aspects of non-playful social behavior. These results suggest that in juvenile rats playful and non-playful forms of social behavior are differentially regulated. In addition, opioid systems may be involved at different levels in the regulation of social play.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245191
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  • 3
    Electronic Resource
    Electronic Resource
    Role of repeated exposure to morphine in determining its affective properties: place and taste conditioning studies in rats (1991)
    Springer
    Psychopharmacology 103 (1991), S. 183-186 
    Details
    ISSN: 1432-2072
    Keywords: Sensitization to drug reward ; Morphine ; Place conditioning ; Taste conditioning ; Abuse potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague Dawley rats were injected daily with saline (morphine naive rats) or 20 mg/kg morphine (morphine experienced rats), starting at least 12 days before training. Subsequent place and taste conditioning indicated that 2.5 mg/kg morphine caused a significant increase in the amount of time spent on the least preferred side by morphine experienced but not by morphine naive rats; furthermore, saccharin consumption was markedly decreased and slightly increased by 10–20 mg/kg morphine in naive and experienced rats, respectively. It was concluded that morphine experience enhances the reinforcing efficacy of morphine and broadens the conditions under which the drug is reinforcing; thus it possibly increases morphine abuse potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244201
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  • 4
    Electronic Resource
    Electronic Resource
    Cell deletion by apoptosis during regression of rat parotid sialadenosis (1995)
    Springer
    Virchows Archiv 427 (1995), S. 181-186 
    Details
    ISSN: 1432-2307
    Keywords: Isoproterenol ; Apoptosis ; Rat ; Parotid ; Sialadenosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Enlargement of the rat parotid salivary glands was induced by repeated administration of isoproterenol. Mean wet weights of the treated glands increased steadily to 240% of control values. Following withdrawal of the drug, quantitative histological techniques were used to investigate the balance between hypertrophy, hyperplasia and apoptosis. The volume occupied by acinar cells relative to the total gland volume together with cytoplasmic|:|nuclear area ratios as measures of hypertrophy increased during the early experimental period. Similarly, serous acinar cell mitotic counts increased, indicating that hyperplasia had occurred. Apoptosis was demonstrated at light microscopical level to be the main mechanism for cell deletion as the glands returned to normal size and weight. The results indicate that hypertrophy and hyperplasia of serous acinar cells contribute to isoproterenol-induced sialadenosis. The experimental animal model demonstrates that these proliferative changes are completed by 48 h and thereafter are balanced by apoptosis as the glands recover their normal size and weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196524
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  • 5
    Electronic Resource
    Electronic Resource
    Expression of the α-subunit of glycoprotein hormones in the pars tuberalis-specific glandular cells in rat, mouse and guinea-pig (1994)
    Springer
    Cell & tissue research 278 (1994), S. 617-624 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Pituitary ; Pars tuberalis ; α-Subunit ; Immunocytochemistry ; In situ hybridization ; Rat ; Mouse ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The nature of the hormone(s) secreted by the pars tuberalis (PT) is still unknown. This pituitary lobe is mainly formed by specific glandular cells that differ in their ultrastructural features from the other adenohypophysial cell types. Data from the literature indicate the presence of thyroid-stimulating hormone immunoreactivity in the PT-specific cells of the rat and the Djungarian hamster but not of other species, including the mouse and guinea-pig. The PT also encloses variable numbers of pars distalis cells, essentially gonadotrophs that are mainly dispersed in its caudal area. We studied the expression of the glycoprotein hormone α-subunit in the PT of the rat, mouse and guinea-pig by in situ hybridization and immunocytochemistry. In situ hybridization, using an oligonucleotide probe complementary to rat cDNA sequence 196–237 revealed the expression of the α-subunit gene throughout the PT of the rat and the mouse; in the guinea-pig, the probe labelled no pituitary cells. Light- and electron-microscopic immunocytochemistry demonstrated α-subunit immunoreactivity in the secretory granules of the PT-specific cells in the three species examined. These cells did not react with a specific antibody against the β-subunit of luteinizing hormone, an antibody that labelled scattered gonadotrophs. The present data suggest that hormone(s) produced by the PT-specific glandular cells are, at least partly, related to glycoprotein hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050253
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  • 6
    Electronic Resource
    Electronic Resource
    Expression of the α-subunit of glycoprotein hormones in the pars tuberalis-specific glandular cells in rat, mouse and guinea-pig (1994)
    Springer
    Cell & tissue research 278 (1994), S. 617-624 
    Details
    ISSN: 1432-0878
    Keywords: Pituitary ; Pars tuberalis ; α-Subunit ; Immunocytochemistry ; In situ hybridization ; Rat ; Mouse ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The nature of the hormone(s) secreted by the pars tuberalis (PT) is still unknown. This pituitary lobe is mainly formed by specific glandular cells that differ in their ultrastructural features from the other adenohypophysial cell types. Data from the literature indicate the presence of thyroid-stimulating hormone immunoreactivity in the PT-specific cells of the rat and the Djungarian hamster but not of other species, including the mouse and guinea-pig. The PT also encloses variable numbers of pars distalis cells, essentially gonadotrophs that are mainly dispersed in its caudal area. We studied the expression of the glycoprotein hormone α-subunit in the PT of the rat, mouse and guinea-pig by in situ hybridization and immunocytochemistry. In situ hybridization, using an oligonucleotide probe complementary to rat cDNA sequence 196–237 revealed the expression of the α-subunit gene throughout the PT of the rat and the mouse; in the guinea-pig, the probe labelled no pituitary cells. Light-and electron-microscopic immunocytochemistry demonstrated α-subunit immunoreactivity in the secretory granules of the PT-specific cells in the three species examined. These cells did not react with a specific antibody against the β-subunit of luteinizing hormone, an antibody that labelled scattered gonadotrops. The present data suggest that hormone(s) produced by the PT-specific glandular cells are, at least partly, related to glycoprotein hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00331382
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  • 7
    Electronic Resource
    Electronic Resource
    The development and purification of a bispecific antibody for lymphokine-activated killer cell targeting against the rat colon carcinoma CC531 (1993)
    Springer
    Cancer immunology immunotherapy 36 (1993), S. 403-408 
    Details
    ISSN: 1432-0851
    Keywords: Bispecific monoclonal antibody ; Lymphokine-activated killer cell ; Rat ; CD8
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo targeting of lymphokine-activated killer (LAK) cells to tumour deposits by bispecific monoclonal antibodies (bimAb) may be a way to improve adoptive immunotherapy. We developed a bimAb against adherent LAK (ALAK) cells and colon tumour CC531 in Wag rats. The bimAb was produced by somatic hybridization of two mouse hybridomas, one producing monoclonal antibodies (mAb) against CD8 (IgG2b, OX8), and the other producing mAb against a CC531-associated antigen (IgG1, CC52). A bimAb-producing clone was selected by an enzyme-linked immunosorbent assay with CC531 tumour cells. BimAb were purified from ascitic fluid by protein A affinity chromatography. Each of five pooled peak fractions was analysed by flow cytometry for the presence of bimAb. Most bimAb were found in a fraction that was eluted at pH 4.5 from protein A. FPLC analysis of this fraction revealed that no parental antibodies were present. The OX8 × CC52 bimAb greatly increased conjugate formation in vitro between ALAK cells and CC531. Results of51Cr-release assays with CC531 as target cells and ALAK cells as effector cells were not significantly different in the presence or in the absence of the bimAb. The methods we used here, a cell enzyme-linked immunosorbent assay and flow cytometry, are simple methods for development and purification of a bimAb when a functional selection method is not a priori available. The OX8 × CC52 bimAb we developed this way may increase in vivo tumour targeting of ALAK cells and thus augment antitumour effect in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01742257
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  • 8
    Electronic Resource
    Electronic Resource
    Soluble factors produced by macrophages/monocytes inhibit lymphokine-activated killer activity in rat splenocyte cultures (1994)
    Springer
    Cancer immunology immunotherapy 38 (1994), S. 61-67 
    Details
    ISSN: 1432-0851
    Keywords: Lymphokine-activated killer activity ; Interleukin-2 ; 2-Mercaptoethanol ; Macrophages/monocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study we investigated the inhibition of interleukin-2(IL-2)-induced lymphokine-activated killer (LAK) activity in rat splenocyte cultures in relation to the presence of 2-mercaptoethanol and macrophages/monocytes. The presence of 2-mercaptoethanol is necessary for induction of LAK activity in rat splenocyte cultures. Removal of macrophages/monocytes from rat splenocytes by plastic or nylon-wool adherence, or iron ingestion resulted in LAK induction by IL-2 in the absence of 2-mercaptoethanol. The effect of macrophages/monocytes on LAK activity was also studied in transwell co-cultures. In the absence of 2-mercaptoethanol, the induction of LAK activity was very low in macrophage/monocyte-depleted splenocytes with macrophages/monocytes in the upper compartment of a transwell culture. In contrast, in the presence of 2-mercaptoethanol a high level of LAK activity was induced in these transwell cultures, showing that 2-mercaptoethanol abolished the LAK-inhibiting capacity of macrophages/monocytes. In addition, established LAK activity was strongly inhibited when, after LAK induction, splenocytes were cultured with supernatant of unfractionated splenocytes, which were cultured with IL-2 but in the absence of 2-mercaptoethanol. Addition of 2-mercaptoethanol abrogated the inhibiting effect of the supernatant completely. These experiments demonstrate that rat macrophages/monocytes produce 2-mercaptoethanolsensitive soluble LAK-inhibiting factors. Ultrafiltration of conditioned culture medium of macrophages/monocytes revealed the presence of LAK-inhibiting factors larger than 10 kDa. We concluded that 2-mercaptoethanol-sensitive soluble factors produced by macrophages/monocytes determine the level of LAK induction in rat splenocyte cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01517171
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  • 9
    Electronic Resource
    Electronic Resource
    Peroxisomes and Hepatotoxicity (1995)
    Springer
    Comparative clinical pathology 5 (1995), S. 189-195 
    Details
    ISSN: 1433-2981
    Keywords: Cell lines ; Guinea pig ; Human ; Hypolipaemic agents ; Peroxisome proliferators ; Rat ; Species difference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Peroxisomes are ubiquitous organelles of eukaryotic cells and are present in significant amounts in hepatic liver cells. Peroxisomal enzymes contribute to several metabolic pathways including fatty acid, purine and amino acid catabolism or bile acid synthesis. The peroxisomal oxidative reactions produce hydrogen peroxide, mostly degraded by catalase which prevents oxidative stress. Moreover, peroxisomes are involved in arylderivative drug detoxification through its epoxide hydrolase activity. In rodents the exposure of cells to xenobiotic compounds such as fibrates, phthalates/adipates and chlorophenoxyacetic acid derivatives, which are used as hypolipaemic drugs, plasticizers and pesticides respectively, lead to a liver mass increase and to a high peroxisome proliferation. This latter event is due to a strong genetic activation triggered by the PPAR (peroxisome proliferator activated nuclear receptor). Human contrasts with rodent since there is no, or little, effect of the above cited compounds. In contrast, the defect of single or multiple peroxisomal functions caused by genetic disorders lead to an increase of very long chain fatty acid level, which is toxic, especially for brain and kidney. The liver response to xenobiotics of the peroxisome proliferator class may be modulated by auxiliary compounds such as hormones (e.g. thyroid hormone) or nutriments (e.g. retinoids).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00368043
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  • 10
    Electronic Resource
    Electronic Resource
    Haematology and clinical chemistry in rats: Comparison of different blood collection sites (1996)
    Springer
    Comparative clinical pathology 6 (1996), S. 160-166 
    Details
    ISSN: 1433-2981
    Keywords: Clinical chemistry ; Haematology ; Rat ; Sampling technique(s)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Blood samples from male and female rats were collected from four different sampling sites by the same technicians and analysed by the same procedures. The sampling sites were the abdominal aorta, orbital venous plexus, dorsal anastomotic orbital vein and sublingual vein. Values obtained in blood samples collected from peripheral sites were compared to those from the abdominal aorta, a sampling site which is normally unaffected by the sampling technique. There were significant differences in haematological parameters, particularly in leucocyte counts which were higher in samples collected from the peripheral sites than in those withdrawn from the central one. No significant changes were observed in coagulation parameters. A significant increase in clinical chemistry parameters related to soft tissue damage, namely creatinine kinase, lactate dehydrogenase, hydroxybutyrate dehydrogenase and aspartate aminotransferase, was seen in samples collected from both orbital sites. From this study it can be concluded that haematological and biochemical values obtained from rats in toxicological studies using different sampling sites are reliable both in males and females, provided that they are compared to values obtained from the same site in untreated controls. Sampling from the orbital plexus proved to be the least invasive method.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00368460
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