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  • 2000-2004  (59)
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  • Rat
  • 1
    Electronic Resource
    Electronic Resource
    ras p21 isoprenylation inhibition induces flat colon tumors in Wistar rats (2000)
    Springer
    Diseases of the colon & rectum 43 (2000), S. 70-75 
    Details
    ISSN: 1530-0358
    Keywords: Pravastatin ; ras p21 isoprenylation ; Colon carcinogenesis ; Flat colon tumor ; Azoxymethane ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The effect of pravastatin, an inhibitor ofras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats. METHODS: Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45. RESULTS: Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associatedras p21 in colon tumors. CONCLUSIONS: These findings suggest that theras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02237247
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  • 2
    Electronic Resource
    Electronic Resource
    Development of the bones and synovial joints in the rat model of the VATER association (2000)
    Springer
    Journal of orthopaedic science 5 (2000), S. 390-396 
    Details
    ISSN: 1436-2023
    Keywords: Key words Adriamycin ; Rat ; Embryo ; VATER association ; Synovial joint ; Bones ; Limbs ; Vertebra ; Sirenomelia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75 mg/kg of adriamycin on days 6–9 or 10–13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6–9, while it was low in the GD 10–13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6–9, and was often associated with a short tail and anal atresia. The joint cavities, and intra-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007760050015
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  • 3
    Electronic Resource
    Electronic Resource
    Induction of adenocarcinoma containing myoepithelial cells in rat submandibular gland by 7,12-dimethylbenz(a)anthracene (2000)
    Springer
    Virchows Archiv 437 (2000), S. 314-324 
    Details
    ISSN: 1432-2307
    Keywords: Keywords 7 ; 12-dimethylbenz(a)anthracene ; Rat ; Submandibular gland ; Adenocarcinoma Myoepithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In an attempt to induce adenocarcinoma containing myoepithelial cells (MECs) in the rat submandibular gland, we injected 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in acetone into the glands of rat pups at the age of 10 days. In both male and female pups, the glands, including their developing terminal secretory units, contained far greater numbers of cells positive for proliferating cell nuclear antigen (PCNA) than did adult glands. A single administration of 1% DMBA (0.05 ml/130 g b.w.) did not produce adenocarcinoma, but did induce occasional sarcomas, such as rhabdomyosarcoma and fibrosarcoma, in 2 months. Most glands regenerated with minimal scar formation. Microscopically, these glands were atypical in that they contained increased numbers of PCNA-positive cells, underdeveloped granular ducts, and striated ducts surrounded by MECs positive for alpha smooth muscle actin (αSMA). Though these features were also observed in the regenerated glands after acetone injection, the number of PCNA-positive cells was relatively high in the glands of DMBA-treated females, especially in the terminal secretory unit. The second DMBA injection at 10 weeks of age produced adenocarcinoma made up of αSMA-positive MECs and keratin 19-positive duct cells. Such MEC-associated adenocarcinoma was induced in the glands of more than half the female but not the male animals. Replacement of either of the double DMBA treatments with acetone, or DMBA treatment, single or double, of adult glands did not produce adenocarcinoma, but did produce sarcoma and squamous cell carcinoma. These results suggest that (1) at least two genetic mutations are necessary for induction of adenocarcinoma with MECs in the rat submandibular gland, (2) the mutation is efficiently introduced to pup glands whose terminal secretory units exhibit extreme proliferative activity, and (3) the second mutation is difficult to introduce in male glands, whose proliferative activity is relatively low, and/or transformed cells need some female hormone after the mutation to propagate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280000223
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  • 4
    Electronic Resource
    Electronic Resource
    Myocardial enzyme activities in plasma after whole-heart irradiation in rats (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 27-32 
    Details
    ISSN: 1432-1335
    Keywords: Key words Heart irradiation ; Plasma enzyme levels ; Myocardial enzyme levels ; Rat ; AbbreviationsCK creatine kinase ; LDH lactate de-hydrogenase ; AST aspartate aminotransferase ; ALT alanine aminotransferase ; α-HBDHα-hydroxybutyrate dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma levels of myocardial enzymes present after local heart irradiation were studied in a rat model. The purpose was to investigate whether, within days after irradiation, these enzyme levels change to such an extent that they may be helpful in assessing the severity of cardiac damage after radiotherapy. Therefore, activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and α-hydroxybutyrate dehydrogenase (α-HBDH) were determined in the plasma and left ventricular myocardium of rats following local heart irradiation with a single dose of 20 Gy. A dose of 20 Gy is known to cause irreversible cardiac damage and to reduce survival times of the animals. Cardiac enzyme assays were performed directly after and twice daily for up to 2 weeks after radiation. Plasma CK, LDH, AST and α-HBDH levels were increased between 2 h and 24 h after irradiation. Plasma ALT levels remained unchanged. Myocardial enzyme levels, measured between 24 h and 16 days after radiation, did not differ between irradiated and control animals, although acute (first 12 h) reductions were observed in the irradiated group. The elevated enzyme levels in plasma appeared to correlate with the acutely reduced myocardial enzyme levels. Although irradiation with a dose of 20 Gy induced acute rises of cardiac enzyme levels in plasma, it is doubtful that fractionated radiation, as applied clinically for treatment of solid tumors, will induce plasma enzyme elevations that are large enough to indicate the extent of cardiac damage occurring acutely or chronically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008461
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  • 5
    Electronic Resource
    Electronic Resource
    Decreased expression of vascular endothelial growth factor in glomeruli of puromycin aminonucleoside nephrosis (2000)
    Springer
    Clinical and experimental nephrology 4 (2000), S. 29-33 
    Details
    ISSN: 1437-7799
    Keywords: Key words VEGF ; Glomeruli ; Ribonuclease protection assay ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Vascular endothelial growth factor (VEGF) is a selective endothelial growth factor which potently enhances microvascular permeability. In the kidney, VEGF mRNA is known to be highly expressed in visceral epithelial cells in glomeruli. However, the physiological role of VEGF in glomerular function and its involvement in the pathogenesis of proteinuria are not clear. The present studies were designed to determine whether altered expression of VEGF mRNA was observed in the course of puromycin aminonucleoside (PAN) nephrosis in rats (a model of human minimal change nephrosis). Methods. The message level of VEGF in isolated glomeruli of PAN nephrosis rats was measured using a ribonuclease protection assay. Results. VEGF expression began to decrease 4 days after PAN injection and could not be detected in the nephrotic stage of PAN nephrosis (on days 8 and 16). In the remission of stage of PAN nephrosis (on day 28), mRNA was restored to the control level. Conclusions. According to our results, a functional defect in the VEGF expression of visceral epithelial cells was observed in PAN nephrosis. VEGF could be a functional marker of visceral epithelial cells, and the loss of normal expression of VEGF after damage to visceral epithelial cells could affect glomerular endothelial cell function in PAN nephrosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101570050058
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  • 6
    Electronic Resource
    Electronic Resource
    Apoptosis in murine duodenum during embryonic development (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 485-487 
    Details
    ISSN: 1437-9813
    Keywords: Key words Duodenum ; Apoptosis ; Fetus ; Rat ; Duodenal atresia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Duodenum is thought to go through a solid-core stage followed by recanalization during its development. This study investigates the role of apoptosis in normal duodenal development, especially during widening of the lumen, and hence, the possible role of apoptosis in duodenal atresia (DA). Twenty-four time-mated Sprague-Dawley rats were killed from day 13 to day 20 of gestation. Duodenums of 3 fetuses were chosen randomly from each rat and processed. Apoptosis was determined by the terminal deoxytransferase-mediated biotin dUTP nick-end labeling (TUNEL) technique (ApopTag). Apoptosis count and cross-sectional areas were measured with an image analyzer (MetaMorph). The number of apoptotic cells per unit area duodenum peaked on day 15 for the mucosal/submucosal layer and on day 14 for the muscular/mesenchymal layer. The maximal number of apoptotic cells per cross-section of duodenum was between 7 and 8. The cross-sectional areas of the duodenal wall and lumen increased exponentially between day 17 and day 19 while duodenal-wall thickness remained relatively constant throughout duodenal development. The localization, timing, and intensity of apoptosis do not suggest that apoptosis is responsible for the widening of the duodenal lumen; enlargement of the lumen is related to the increase in duodenal circumference. Apoptosis thus may not be involved in the pathogenesis of DA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830000408
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  • 7
    Electronic Resource
    Electronic Resource
    Organ-specific distribution of major histocompatibility antigens in rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 285-292 
    Details
    ISSN: 1437-9813
    Keywords: Key words Major histocompatibility complex (MHC) ; Rat ; Immunohistochemistry ; Distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study systematically investigated the expression and distribution of the major histocompatibility complex (MHC) classes I and II in the rat. About 150 native tissue probes from eight adult Lewis rats were taken, representative for most organs, tissues, and the vascular system. MHC expression was analyzed by two monoclonal antibodies (mAb) generated against the non-polymorphic determinants of rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen), histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations on various tissues and the alkaline phosphatase-anti-alkaline phosphatase technique allowed semiquantitative evaluation of serial cryostat tissue sections. MHC class I expression was detected on most immunocompetent cells. Endothelial cells were stained heterogeneously along the vascular system and the organ-specific microcirculation. Furthermore, some organs showed staining of parenchymal cells. MHC class II was found on all immunocompetent cells positive for the B-cell marker and about 15% of cells positive for the histiocytic markers. Besides the well-known expression of MHC class II in the outer zone of the renal proximal tubule, further organ-specific cell forms were found positive. In conclusion, the present study outlines tissue-specific distribution of MHC I/II and implies that each organ carries a variable immunologic burden that needs to be considered for any transplantation model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050746
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  • 8
    Electronic Resource
    Electronic Resource
    Proliferation, zonal maturation, and steroid production of fetal adrenal transplants in adrenalectomized rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 293-296 
    Details
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Proliferation ; Adrenal glands ; Addisonian crisis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study investigated the histologic maturation, proliferative capacity, and steroid production of fetal adrenal transplants (Tx) in adrenalectomized rats. A pair of fetal adrenal glands (18–20 days of gestation) was transplanted into the omentum of syngeneic Lewis rats (n=45). Four weeks later, in 5 animals the grafts were excised for morphologic evaluation. Proliferation was investigated by immunohistochemical staining for KI-67 protein and quantified by the proliferation index (PI = positive cells/100 counts). All other hosts (Tx; n = 40) underwent bilateral adrenalectomy (AE) to induce Addisonian crisis. Postoperatively, survival and concentrations of potassium, sodium, aldosterone, and corticosterone were recorded for 6 months. These data were compared to controls (C = only AE; n = 30) and a sham group (S; n = 10). At the end of the study period all surviving hosts were killed for histologic examination of grafts. At 4 weeks post-Tx the adrenal grafts demonstrated a distinct zona glomerulosa and frequent proliferation with a PI of 0.084, comparable to normal control (0.092). Following AE survival was significantly prolonged in Tx (86% vs 12% of C, P 〈 0.05). Control animals developed severe hyponatremia and hyperkalemia, whereas in Tx only transient signs of Addisonian crisis were recorded. Levels of aldosterone dropped within 7 days in the Tx and C groups, but returned to normal for Tx within 8 weeks. Corticosterone levels of Tx animals fell to 25% within week, but steadily increased to 70% by the end of the study. At 6 months, grafts revealed a mature adrenocortical structure with little proliferative activity, which was comparable to controls. In a syngeneic rat model fetal adrenal transplants thus mature and proliferate to provide sufficient steroid production for adrenalectomized hosts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050747
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  • 9
    Electronic Resource
    Electronic Resource
    Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia in rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 414-416 
    Details
    ISSN: 1437-9813
    Keywords: Key words Congenital diaphragmatic hernia ; Hypoplastic lung ; Bromodeoxyuridine (BrdU) ; Antenatal glucocorticoids ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 ± 3.01) compared to groups I (9.16 ± 2.20) and III (6.83 ± 1.70) (P 〈 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003839900336
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  • 10
    Electronic Resource
    Electronic Resource
    Long-term small bowel allograft function induced by short-term FK 506 application is associated with split tolerance (2000)
    Springer
    Transplant international 13 (2000), S. S532 
    Details
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Split tolerance ; FK 506 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0–5 in the rejection model and from days 0–9 in the long-term functional model. Mean survival time in the rejection model was 98 ± 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term ( 〉 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely ( 〉 70 days). In vitro, mixed leukocyte reactivity of CD4 + T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050396
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  • 11
    Electronic Resource
    Electronic Resource
    Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model (2000)
    Springer
    Transplant international 13 (2000), S. S528 
    Details
    ISSN: 1432-2277
    Keywords: Key words Implantation model ; Aortic valves ; Valve dysfunction ; Rejection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050395
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  • 12
    Electronic Resource
    Electronic Resource
    Hypoxia-reoxygenation differentially stimulates stress-activated protein kinases in primary-cultured rat hepatocytes (2000)
    Springer
    Transplant international 13 (2000), S. S597 
    Details
    ISSN: 1432-2277
    Keywords: Key words Hypoxia-reoxygenation ; JNK1/SAPK1 ; Rat ; Hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Organ injury after ischemia and reperfusion (I/R) remains one of the most important limiting factors in liver surgery and transplantation. Oxygen-free radical (OFR) generation is considered a major cause of this damage. JNK1/SAPK1, a member of MAPK family, regulates cell adaptation to stressful conditions. The aim of this study was to determine if hypoxia-reoxygenation (H/R) can activate JNK1/SAPK1 and if OFR are involved in this activation. Primary cultured rat hepatocytes isolated from other liver cells and blood flow were submitted to warm and cold H/R phases mimicking surgical and transplant conditions. JNK1/SAPK1 was activated by both warm and cold H/R. Deferoxamine (1 mM), di-phenyleneiodonium (50 μM) and N-acetylcysteine (10 mM) significantly inhibited this kinase activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050410
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  • 13
    Electronic Resource
    Electronic Resource
    Real-time monitoring of nitric oxide in ischemia-reperfusion rat kidney (2000)
    Springer
    Urological research 28 (2000), S. 141-146 
    Details
    ISSN: 1434-0879
    Keywords: Key words Kidney ; Nitric oxide ; Ischemia-reperfusion injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we attempted to clarify the release of nitric oxide (NO) and its role in the ischemia-reperfusion rat kidney. After right nephrectomy, male Wistar rats were divided into four groups: one sham operated and three groups who underwent ischemia (30 min) and reperfusion of the left renal artery. Thirty minutes prior to ischemia-reperfusion, two groups were injected intraperitoneally with 10 and 30 mg/kg of NG-nitro-l-arginine methylester (L-NAME). Real-time monitoring of blood flow and NO release in the rat kidney was measured with a laser Doppler flowmeter and an NO-selective electrode, respectively. Serum creatinine and blood urea nitrogen (BUN) levels were measured 1 and 7 days after the induction of ischemia-reperfusion. Clamping of the renal artery decreased blood flow to 1–5% of the basal level measured before clamping. After removal of the clip, the blood flow of the 30 mg/kg L-NAME rats was significantly lower than that of the controls. Immediately following the clipping of the renal artery, NO release rapidly increased. After removing the clip, NO release immediately returned to three-quarters of the basal level. Serum creatinine and BUN levels of the ischemia-reperfusion rats were slightly but not significantly higher and those of 30 mg L-NAME rats were significantly higher than those of the control or ischemia-reperfusion rats 1 day and 7 days after ischemia-reperfusion. Our data suggest that NO acts as a cytoprotective agent in ischemia-reperfusion injury of the rat kidney.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050153
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  • 14
    Electronic Resource
    Electronic Resource
    Systemic treatment with epidermal growth factor but not insulin-like growth factor I decreases the involution of the prostate in castrated rats (2000)
    Springer
    Urological research 28 (2000), S. 75-81 
    Details
    ISSN: 1434-0879
    Keywords: Key words Castration ; Epidermal growth factor ; Insulin-like growth factor I ; Prostate ; Testosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are strong inducers of proliferation to prostate cells cultured in serum-free medium. Accordingly we wanted to study the growth of the prostate gland in castrated rats after treatment with EGF, IGF-I and testosterone. Castrated Wistar rats were treated with growth factors (EGF 35 μg/rat per day; IGF-I 350 μg/rat per day) or testosterone (2 mg/rat per day) for 3 days either immediately after or 10 days after castration. Prostate tissue was examined by stereological and immunohistochemical techniques and by enzyme-linked immunosorbent assay (ELISA). Treatment with EGF inhibited the involution of the prostate (P 〈 0.05), whereas treatment with IGF-I did not affect the prostate involution as compared to castrated controls. EGF treatment significantly increased the endogenous rat EGF in the ventral prostate, but cellular proliferation was not affected. Testosterone treatment increased the weight of the prostate, by increase of all tissue components of the prostate, and significantly increased cellular proliferation. Systemic administration of EGF but not IGF-I decreased the involution of the rat prostate induced by castration. Compared with testosterone, the effects of EGF treatment on the prostate involution were moderate, and the effects of EGF were not related to cellular proliferation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050141
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  • 15
    Electronic Resource
    Electronic Resource
    Effect of aging on bladder function and the response to outlet obstruction in female rats (2000)
    Springer
    Urological research 28 (2000), S. 33-37 
    Details
    ISSN: 1434-0879
    Keywords: Key words Bladder ; Rat ; Aging ; Obstruction ; Cystometrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bladder dysfunction in the aging population is a significant problem. However the concomitant presence of other diseases in many patients can make it difficult to distinguish between changes in bladder function and other influences. The present study was designed to study, in aging rats, bladder function and the effect of partial bladder outlet obstruction (BOO) on bladder function. Cystometrics were performed in awake, female Fischer 344 rats of four age groups (6, 12, 18 and 24 months) following subcutaneous implantation of a mediport catheter. Cystometric evaluations were carried out in control rats or those subject to three weeks of BOO. Bladder compliance significantly decreased with aging, which reflected an increase in threshold pressure without changes in bladder capacity. Partial BOO caused development of severe bladder instability. Following BOO, bladder capacity and compliance were significantly increased in all age groups. Threshold pressure was lower in obstructed animals, except for 6-month rats. Younger animals were able to generate a higher contraction pressure to compensate for the BOO, whereas older animals did not. Using an awake model of cystometric measurement, we have demonstrated that aging, by itself can affect bladder function. Furthermore, aged animals respond differently to BOO than younger animals. These results demonstrate that both aging and disease can contribute to bladder dysfunction, and suggest that treatment of bladder dysfunction may require a combination of therapies targeted to multiple etiologies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050007
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  • 16
    Electronic Resource
    Electronic Resource
    Morphological analysis of peripheral nerve regenerated by means of vein grafts filled with fresh skeletal muscle (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 475-482 
    Details
    ISSN: 1432-0568
    Keywords: Key words Nerve repair ; Nerve fiber regeneration ; Sciatic nerve ; Muscle-vein-combined graft ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical data have shown that a vein segment filled with fresh skeletal muscle can be considered a good autologous grafting conduit for the repair of peripheral nerve lesions. In this study, the long-term morphological organization of rat sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is further analysed by light and electron microscopy. Regenerated nerve fibers were organized into fascicles of various sizes that were clearly delimited by perineurial-like shells made by long and thin cytoplasmic processes of perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted skeletal muscle fibers were still detectable among nerve fiber fascicles. However, in spite of the persistence of skeletal muscle along the graft, regenerated nerve fibers showed a good morphological pattern of regeneration, providing further evidence that the muscle-vein-combined grafting technique represents an effective surgical alternative to the classical fresh nerve autograft for the repair of peripheral nerve defects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050334
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  • 17
    Electronic Resource
    Electronic Resource
    Immunocytochemical distribution of the GABAB receptor splice variants GABAB R1a and R1b in the rat CNS and dorsal root ganglia (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 1-13 
    Details
    ISSN: 1432-0568
    Keywords: Key words GABAB receptor ; CNS ; Dorsal root ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The anatomical distribution of the GABAB receptor (GBR) splice variants GBR1a and 1b in the CNS has not previously been studied. In the present study, distribution of the splice variants was mapped using immunohistochemistry. Polyclonal antibodies against splice variant unique epitopes were raised in rabbits. Affinity purified antibodies were used according to routine immunohistochemical procedures in sections from the rat CNS or dorsal root ganglia (DRG). The staining intensity was high in the cerebral cortex but lower in basal ganglia and the hippocampus. In the cerebellum, there was a marked difference in the distribution of GBR1a- and 1b-like immunoreactivity (LI). GBR1a-LI was preferentially localised in the granule cell layer whilst GBR1b-LI was mostly found in Purkinje cells and in the molecular layer. Cell bodies of the deep cerebellar nuclei stained for the GBR1a antibody while terminals surrounding the cell bodies were strongly labelled with the GBR1b antibody. A similar pre- vs postsynaptic pattern was seen in several nuclei ventral or caudal to the cerebellum (e.g. the cochlear nucleus, the facial nucleus, the spinal cord) but not in regions rostral to the cerebellum. In the spinal cord, strong labelling for both antibodies was seen in the dorsal horn. The GBR1b but not the GBR1a antibody stained tanycytes in the epithelium of the 3rd ventricle and in the central canal at the brain stem level. DRG neurons were positive for both the GBR1a and 1b antibody, but the former stained the cells much more intensely. Satellite cells were labelled with the GBR1b antibody. The most important aspect of these findings is that in some nuclei, GBR1b may mediate inhibition of transmitter release while in the same regions, GBR1a may mediate postsynaptic inhibition. Further, the observations support previous findings that GBR1b is the predominant splice variant in Purkinje cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008224
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  • 18
    Electronic Resource
    Electronic Resource
    NK1, NK2 and NK3 tachykinin receptor localization and tachykinin distribution in the ileum of the mouse (2000)
    Springer
    Anatomy and embryology 202 (2000), S. 247-255 
    Details
    ISSN: 1432-0568
    Keywords: Key words Enteric neurons ; Interstitial cells of Cajal ; Smooth muscle cells ; Guinea-pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tachykinin receptors NK1r, NK2r and NK3r bind tachykinins with different affinities and share pharmacological and molecular differences among animal species. NK1r, NK2r, NK3r and tachykinin (SP/NKA) distribution was studied by immunohistochemistry in the ileum of mouse since no data are available for this species. The results were then compared to those obtained in the rat and guinea pig either by us or by others to ascertain interspecies similarities and/or differences. NK1r- and NK3r-immunoreactivity (IR) were detected in neurons and NK1r-IR in the interstitial cells of Cajal at the deep muscular plexus. At variance with rat and guinea pig, NK1r-IR was also found in the myoid cells of the villi, while NK2r-IR was never detected in nerve varicosities. This latter datum suggests that the NK2r does not play a presynaptic role in the mouse. Unexpectedly, a high NK2r-IR and the presence of NK3r-IR were observed at the inner portion of the circular muscle layer in the mouse as well as in the rat and guinea pig, demonstrating a subregional distribution of these receptors. Tachykinin distribution did not show noticeable species-related differences. The present findings show species-related differences in the tachykinin receptor distribution that might be related to a different tachykinin controlof intestinal motility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290000106
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  • 19
    Electronic Resource
    Electronic Resource
    Systemic hypothermia following spinal cord compression injury in the rat: an immunohistochemical study on MAP 2 with special reference to dendrite changes (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 546-552 
    Details
    ISSN: 1432-0533
    Keywords: Key words Hypothermia ; Immunohistochemistry ; Microtubule-associated protein 2 (MAP2) ; Rat ; Spinal cord injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 °C to 30 °C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000206
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  • 20
    Electronic Resource
    Electronic Resource
    Changes of Fas and Fas ligand immunoreactivity after compression trauma to rat spinal cord (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 75-81 
    Details
    ISSN: 1432-0533
    Keywords: Key words Fas ; Fas ligand ; Rat ; Spinal cord ; Trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This immunohistochemical study evaluated Fas and Fas ligand (FasL) in the rat nervous system and their changes in the spinal cord subjected to compression. Normal spinal cord showed a low level of Fas and FasL immunoreactivity in the white matter except in the corticospinal tracts. Fas and FasL immunoreactivity seemed to be located in axons and their myelin sheaths. Other regions of the nervous system did not show immunoreactivity to Fas and FasL. Moderate and severe compression injury of the spinal cord resulted in a reduction of Fas and FasL immunoreactivity in the white matter of injured T8–9 segments at 4 h and a complete loss at 1 day after trauma. This was seen even in the remaining white matter. In contrast, increased immunoreactivity to Fas and FasL was present in the cranial T7, caudal T10 (moderate injury) and T12 (severe injury) segments at day 4 with most intense staining were seen at day 9 after trauma. Increased Fas and FasL immunoreactivity may have pathophysiological implications for the development of secondary injuries after trauma to the spinal cord. Fas-FasL interactions may for instance be involved in apoptosis of oligodendrocytes which occurs as a delayed phenomenon after trauma to the spinal cord. The integrity of myelin sheaths may in this way be jeopardized by apoptosis of oligodendrocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051195
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  • 21
    Electronic Resource
    Electronic Resource
    Maximum tolerated doses of methotrexate and 7-hydroxy-methotrexate in a model of acute toxicity in rats (2000)
    Springer
    Cancer chemotherapy and pharmacology 46 (2000), S. 69-73 
    Details
    ISSN: 1432-0843
    Keywords: Key words 7-Hydroxymethotrexate ; Methotrexate ; Maximum tolerated dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: After more than 50 years of methotrexate (MTX) treatment of acute lymphoblastic leukaemia (ALL), it is currently believed that as long as dose escalations are followed by adequate leucovorin rescue guided by monitoring MTX serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD-MTX) can be tolerated without life-threatening toxicity. However, our recent experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1 mM, which is below the levels routinely found in patients on HD-MTX, demonstrate intolerable toxicity and some animals die within 8 h. Electron microscopy indicates that endothelial cell and platelet functions are perturbed. Since animal data are lacking, and interspecies differences not known, we wanted to investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of short-term effects. The maximum tolerated dose was chosen instead of LD50 for reasons of animal welfare. Methods: We infused MTX and 7-OH-MTX into anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were given as a bolus plus continuous infusion. The dose-finding ranges were 1.8–11.3 g/kg MTX and 0.1–1.2 g/kg 7-OH-MTX. Results: The maximum tolerated dose was between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or 7-OH-MTX doses and concentrations died after sudden reductions in heart rate and blood pressure. Conclusions: We demonstrated a lower maximum tolerated dose of 7-OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the therapeutic range after HD-MTX. If the rat/human interspecies differences are not large, our data may indicate that HD-MTX regimens should not be further dose intensified, due not so much to the effects of MTX as to those of 7-OH-MTX.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800000111
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  • 22
    Electronic Resource
    Electronic Resource
    A polymorphism of the rat T-cell receptor β-chain variable gene 13 (BV13S1) correlates with the frequency of BV13S1-positive CD4 cells (2000)
    Springer
    Immunogenetics 51 (2000), S. 296-305 
    Details
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050623
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  • 23
    Electronic Resource
    Electronic Resource
    Constitutive NF-κB activity is modulated via neuron-astroglia interaction (2000)
    Springer
    Experimental brain research 130 (2000), S. 100-104 
    Details
    ISSN: 1432-1106
    Keywords: Key words NF-κB ; p65 ; Hippocampal neurons ; Glia ; Astrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  NF-κB is found in many neuronal cell types in different states of activity. This study aimed to define which conditions induce constitutive NF-κB activity in cultured hippocampal neurons using activity-specific antibody staining. In co-culture with astroglia, hippocampal neurons were devoid of activated NF-κB. In these co-cultures, NF-κB could not be activated via kainate or glutamate. In contrast, separating neurons from the glial compartment resulted in a time-dependent increase of activated neuronal NF-κB. In this line, activation of NF-κB by kainate or glutamate is very effective in freshly separated cultures, but inhibited when the cultures are reassembled after stimulation. These findings suggests that a neuronal-glial interaction may regulate gene expression via NF-κB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050011
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  • 24
    Electronic Resource
    Electronic Resource
    Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat (2000)
    Springer
    Histochemistry and cell biology 122 (2000), S. 507-517 
    Details
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00418-004-0708-7
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  • 25
    Electronic Resource
    Electronic Resource
    Resistance to growth hormone and insulin-like growth factor-I in acidotic rats (2000)
    Springer
    Pediatric nephrology 14 (2000), S. 720-725 
    Details
    ISSN: 1432-198X
    Keywords: Key words Metabolic acidosis ; Growth ; Growth hormone ; Insulin-like growth factor-I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth impairment induced by chronic metabolic acidosis is associated with an abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To examine the potentially beneficial effects of IGF-I on acidosis-induced growth impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis, three groups of acidotic young rats (untreated, AC, n=12; treated with recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8) were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair-fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH-binding protein (GHBP), and IGF-I concentrations (mean±SEM) were analyzed. Significant decreases of 4.7-kb GH receptor [26±2 vs. 49±6 arbitrary densitometry units (ADU)] and 7.5 kb IGF-I (41±3 vs. 104±10 ADU) transcripts and low serum GHBP (25±1 vs. 32±1 ng/ml) and IGF-I (279±50 vs. 366±6 nmol/l) levels were found in the AC compared with the C rats. The majority of these alterations were also observed in PF rats. Compared with acidotic untreated rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I. In contrast, IGF-I administration depressed the hepatic expression of all GH and IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of associated malnutrition, and induced growth retardation that is resistant to GH therapy. Our study also shows that administration of IGF-I does not accelerate the growth of acidotic rats, suggesting a peripheral mechanism, at the level of target tissues, is responsible for the resistance to the growth-promoting actions of GH and IGF-I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00013425
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  • 26
    Electronic Resource
    Electronic Resource
    Apoptosis parallels ceramide content in the developing rat kidney (2000)
    Springer
    Pediatric nephrology 15 (2000), S. 188-191 
    Details
    ISSN: 1432-198X
    Keywords: Key words Apoptosis ; Ceramide ; Development ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ceramide is emerging as an important hydrophobic sphingolipid involved in cell differentiation and apoptosis. Since apoptosis plays a significant role in cellular remodeling during renal morphogenesis, we measured ceramide content and apoptosis in the fetal (18 days gestation), neonatal (3, 7, and 14 days postnatal), and adult rat kidney. In addition, to determine whether developmental changes in ceramide content are tissue-specific, we compared renal ceramide content with that in lung and liver. Ceramide was measured by the diacylglycerol kinase assay, and apoptosis was determined by the TUNEL technique. Renal ceramide content fell over 100-fold from the fetus to the 7th postnatal day. Renal apoptosis paralleled ceramide content, with a greater than 300-fold decrease in apoptosis from fetal to adult life. Ceramide content of the lung and liver was significantly less than that of the kidney, and changed less with maturation. We conclude that maturational changes in ceramide content are tissue-specific, and that the high rate of apoptosis in the developing kidney may be related to the elevated ceramide content.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004670000444
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  • 27
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    Electronic Resource
    Environmental modulation of the response to amphetamine: dissociation between changes in behavior and changes in dopamine and glutamate overflow in the rat striatal complex (2000)
    Springer
    Psychopharmacology 151 (2000), S. 166-174 
    Details
    ISSN: 1432-2072
    Keywords: Keywords Novelty ; Context ; Environment ; Stress ; 6-OHDA ; Rotational behavior ; Striatum ; Nucleus accumbens shell ; Caudate ; Amphetamine ; Dopamine ; Glutamate ; Aspartate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900359
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  • 28
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    Electronic Resource
    Human interferon-α increases immobility in the forced swimming test in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 106-110 
    Details
    ISSN: 1432-2072
    Keywords: Key words Interferon ; Depression ; Forced swimming test ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objectives: We examined the immobility of the forced swimming test induced in an animal model by human interferon (IFN), which has often been reported to induce depression in clinical use. Methods: In the present study, we examined the effects of human IFNs on results of the forced swimming test in rats. Results: Single intravenous (IV) administration of human IFN-α (6×104 IU/kg), but not of human IFN-β or -γ, significantly increased immobility time in the forced swimming test in rats. Repeated administration of human IFN-α (6×103 IU/kg) also significantly increased the immobility time. On the other hand, none of the rat IFNs (rat IFN-α, -β and -γ, 6×104 IU/kg, IV) changed the immobility time. Neither human IFNs nor rat IFNs changed the locomotor activity of rats. Conclusions: These findings suggest that human IFN-α has a greater potential for inducing increase of the immobility in the rat forced swimming test than human IFN-β and -γ, and that the effect of human IFN-α might not be mediated through IFN-α/β receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050031
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  • 29
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    Electronic Resource
    Selective mu and delta, but not kappa, opiate receptor antagonists inhibit the habituation of novelty-induced hypoalgesia in the rat (2000)
    Springer
    Psychopharmacology 148 (2000), S. 99-105 
    Details
    ISSN: 1432-2072
    Keywords: Key words Opiate receptor ; Antinociception ; Habituation ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: There is now extensive evidence demonstrating that exposure to novel stimuli induces hypoalgesia and that this effect habituates over repeated exposure to the stimuli. Moreover, it has been shown that administration of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia. Objectives: The present experiments were conducted to determine the relative influence of different opiate receptor subtypes in the attenuation of the habituation of novelty-induced hypoalgesia. Methods: In experiments 1–3, different groups of male, Wistar rats (275–300 g) were administered vehicle, 0.5, 1.0 or 2.0-nmol doses of the µ-selective antagonist Cys2-Tyr3-Orn5-Pen7-amide (CTOP), the δ-receptor selective antagonist naltrindole, or the κ-selective antagonist nor-binaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections were delivered to the right lateral ventricle 30 min prior to exposure to a novel hot-plate apparatus (48.5°C), once a day for eight consecutive days. Results: Paw-lick latencies in vehicle-treated animals were long during the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was significantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of CTOP, by a 2.0-nmol dose of naltrindole, but was unaffected by all doses of nor-BNI. Conclusions: These results support the involvement of the µ and δ, but not the κ, opiate receptor subtypes in the habituation of novelty-induced hypoalgesia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050030
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  • 30
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    Electronic Resource
    Acute exposure to saccharin reduces morphine analgesia in the rat: evidence for involvement of N-methyl-d-aspartate and peripheral opioid receptors (2000)
    Springer
    Psychopharmacology 149 (2000), S. 56-62 
    Details
    ISSN: 1432-2072
    Keywords: Key words Morphine ; Opioid receptor ; NMDA ; Tolerance ; Rat ; Tail flick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug’s peripheral effect, while learned tolerance involves activation of N-methyl-d-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist. Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation. Methods: Six experiments used the rat’s tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the non-competitive NMDA receptor antagonist MK-801 on this modulation of analgesia. Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment 1a), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin. Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900337
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    Electronic Resource
    Opiate withdrawal-induced place aversion lasts for up to 16 weeks (2000)
    Springer
    Psychopharmacology 149 (2000), S. 115-120 
    Details
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900358
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  • 32
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    Role of dopamine in prepulse inhibition of acoustic startle (2000)
    Springer
    Psychopharmacology 149 (2000), S. 181-188 
    Details
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Prepulse inhibition of acoustic startle is the reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Prepulse inhibition occurs normally in humans and experimental animals, but schizophrenic persons often exhibit a marked impairment in this measure. Previous studies have shown that dopamine (DA)-dependent neuronal mechanisms are involved in the modulation of prepulse inhibition. Objective: Experiments were conducted in rats to elucidate further the involvement of DA-ergic mechanisms in prepulse inhibition. Results: In line with previous studies, the indirect DA agonist, amphetamine, was shown to decrease prepulse inhibition. A close reverse relationship over time between DA overflow in the nucleus accumbens and prepulse inhibition was obtained using a technique allowing concomitant measurement of these parameters in awake, freely moving rats. This effect was more pronounced in amphetamine-treated rats compared to rats treated with equimolar doses of cocaine, which increased DA overflow without affecting prepulse inhibition. In other experiments, the combined treatment with subthreshold doses of the selective DA D1 agonist, SKF 38393, and the selective DA D2 agonist, quinpirole, was also shown to decrease prepulse inhibition. Finally, the selective DA D2 antagonist, raclopride, was shown to enhance prepulse inhibition. Conclusions: In line with previous studies, it is concluded that DA neurotransmission is involved in the modulation of prepulse inhibition and that the ventral part of the mesostriatal DA system may serve an important role in this modulation. Furthermore, the possibility is discussed that the discrepant results on prepulse inhibition obtained with amphetamine and cocaine may disclose functionally relevant differences in their mechanisms of action, and that the enhancement of prepulse inhibition induced by some antipsychotics in rats may reflect their propensity to induce adverse mental effects in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000369
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    Prefrontal dopamine is directly involved in the anxiogenic interoceptive cue of pentylenetetrazol but not in the interoceptive cue of chlordiazepoxide in the rat (2000)
    Springer
    Psychopharmacology 149 (2000), S. 366-376 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prefrontal cortex ; Dopamine ; Anxiety ; Drug discrimination ; Pentylenetetrazol ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The prefrontal cortical (PFC) dopamine (DA) system has been implicated in anxiety-related behavioral changes, but direct, unequivocal support for this idea is sparse. Objectives: The present aim was to study the functional significance of prefrontal DA using the pentylenetetrazol (PTZ) discrimination model of anxiety. A comparison was made with its role in the cue of the anxiolytic drug chlordiazepoxide (CDP). Methods: Two groups of rats were trained to discriminate either PTZ (20 mg/kg, s.c.) or CDP (10 mg/kg, i.p.) from saline using an operant drug discrimination procedure. After prolonged training, half of each group was used to assess biochemical changes induced by both drugs in different sub areas of the PFC. For the remaining rats, discrimination training continued and generalization tests with PTZ and CDP were performed. Rats were then provided with bilateral guide cannulae aimed at the ventromedial (vm) PFC, and the effects of local infusions of DAergic drugs on discriminative performance were evaluated. Results: CDP did not affect PFC DA activity, but PTZ increased the DOPAC/DA ratio in the vmPFC selectively. Generalization tests showed that the cues of PTZ and CDP were dose dependent. In PTZ-trained rats, infusions of the DA receptor antagonist cis-flupenthixol into the vmPFC blocked the PTZ cue dose dependently, whereas the agonist apomorphine partially generalized to this cue. In CDP-trained rats, neither drug antagonized or generalized to the CDP cue, showing that PFC DA is not critically involved in the CDP cue and that local pharmacological manipulations of PFC DA do not affect discriminative abilities per se. Conclusions: The DAergic innervation of the PFC is directly involved in the behavioral effects of PTZ, suggesting a role for it in anxiety.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000390
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    In vivo estimates of efficacy at 5-HT1A receptors: effects of EEDQ on the ability of agonists to produce lower-lip retraction in rats (2000)
    Springer
    Psychopharmacology 149 (2000), S. 377-387 
    Details
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A agonist ; Intrinsic activity ; Efficacy ; Irreversible antagonism ; Lower-lip retraction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Maximal responses are often used as a measure of intrinsic activity or efficacy, but cannot be directly equated to efficacy. Using irreversible antagonists, estimates of efficacy can be obtained that may be less dependent on specific conditions. Objectives: To characterize the intrinsic activity of serotonin (5-HT)1A agonists by examining the effects of an irreversible antagonist on their ability to produce 5-HT1A receptor-mediated responses. Methods: The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the ability of 5-HT1A agonists to produce lower-lip retraction (LLR) in rats were studied. Results: In the absence of EEDQ, each 5-HT1A agonist produced full effects, the rank order of potency being: S 14506 〉 8-OH-DPAT 〉 buspirone 〉 ipsapirone. EEDQ decreased the number of 5-HT1A binding sites and shifted the dose–response curves (DRCs) of each agonist either to the right or, at higher EEDQ doses, to the right and downward. The manner in which these shifts occurred, however, differed among the compounds. For each agonist, all DRCs obtained after different doses of EEDQ were fitted to models proposed by Furchgott and Black and Leff, and the results indicated the following rank order of efficacy: ipsapirone 〈 buspirone ≈ 8-OH-DPAT 〈 S 14506. 5-HT1A agonist-induced LLR appears to be mediated by 5-HT1A receptors, because the 5-HT1A antagonist, WAY 100635, shifted the agonist DRCs to the right in a parallel and dose-related manner, with pA2 values ranging from 7.8 to 8.1. Moreover, pretreatment with WAY 100635 protected against the antagonist activity of EEDQ. Conclusions: The results suggest that the effects of EEDQ on the ability of 5-HT1A agonists to produce LLR in rats may be useful to obtain estimates of their apparent efficacy at 5-HT1A receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000374
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    Repeated dose (28 days) oral toxicity study of flutamide in rats, based on the draft protocol for the `Enhanced OECD Test Guideline 407' for screening for endocrine-disrupting chemicals (2000)
    Springer
    Archives of toxicology 74 (2000), S. 127-132 
    Details
    ISSN: 1432-0738
    Keywords: Key words Flutamide ; Androgen antagonist ; Rat ; Enhanced OECD Test Guideline 407 ; Endocrine disrupters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In association with the international validation project to establish a test protocol for the `Enhanced OECD Test Guideline 407', we performed a preliminary 28-day, repeated-dose toxicity study of flutamide, a non-steroidal androgen antagonist, and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine-disrupting chemicals (EDCs). Seven-week-old CD(SD)IGS rats were divided into four groups, each consisting of 10 males and 10 females, and administered flutamide once daily by oral gavage at doses of 0 (control), 0.25, 1 and 4 mg/kg body weight/day. Male rats were killed 1 day after the 28th administration. Female rats were killed on the day they entered the diestrus stage in the estrous cycle following the last treatment. Male rats receiving flutamide at dose levels of 1 and 4 mg/kg showed lobular atrophy of the mammary gland and a decrease in epididymal weight. In addition, 4 mg/kg flutamide-treated males exhibited raised serum testosterone and estradiol levels and decreased weight of the accessory sex glands. In females, a slight prolongation of the estrous cycle was also observed in the 4 mg/kg flutamide-treated group. No dose-related changes could be detected by haematology, serum biochemistry and sperm analysis. Thus, among the parameters tested in the present experimental system, the weight of endocrine-linked organs and their histopathological assessment, serum hormone levels, and estrous cycle stage allowed the detection of endocrine-related effects of flutamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050664
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    Changes in serum α2u-globulin levels in male rats given diethylstilbestrol and applicability to a screening test for endocrine-disrupting chemicals (2000)
    Springer
    Archives of toxicology 74 (2000), S. 48-53 
    Details
    ISSN: 1432-0738
    Keywords: Key wordsα2u-Globulin ; Diethylstilbestrol ; Endocrine disrupter ; Rat ; Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α2u-Globulin (AUG) is a major rat urinary protein, which has a molecular weight of 16 kDa (kidney type) or 19 kDa (native type). The biosynthesis of this protein is under multi-hormonal regulation. In this study, we investigated changes in serum AUG level and their association with changes in the reproductive organs of male rats after the administration of the estrogenic chemical, diethylstilbestrol (DES) at doses ranging from 0.01 mg/kg per day to 100 mg/kg per day by gavage for 14 days. Our aim was to establish basic data for the development of a new screening method for endocrine disrupting chemicals based on serum AUG levels. DES treatment decreased the weight of testes in a dose-dependent manner; and was accompanied by atrophic histopathological changes in testes. Testis weights were significantly decreased by the group given 1 mg/kg per day DES; however, histopathological abnormalities were found in the group given 0.1 mg/kg per day DES. In four of five animals in the group given 1 mg/kg per day there was no significant decrease in testis weight and only a slight or moderate degeneration of the pachytene spermatocytes. Despite these findings, serum AUG levels in this group decreased markedly, while the serum AUG level markedly decreased even in the animals with no histopathological change in the 1 mg/kg per day or 0.1 mg/kg per day groups with no histopathological change also showed decreased serum AUG level. These results suggest that the serum AUG level may be a sensitive parameter for detecting the activity of estrogenic chemicals in intact male rats. Although a uterotropic assay has been proposed for immature female or ovariectomized female rats and is currently undergoing validation studies internationally, there is no screening method for estrogenic chemicals in intact male animals. More data on AUG changes by treatment with other estrogenic chemicals are needed in order to determine the sensitivity and specificity of this response to estrogens. Nonetheless, an AUG-based screening test for estrogenic chemicals may be useful owing to its applicability to conventional toxicity studies and an apparently higher sensitivity of this parameter compared to organ weight change or histology of testis in intact male rats and applicability to conventional toxicity studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050651
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    The T-type calcium channel blocker mibefradil reduced interstitial and perivascular fibrosis and improved hemodynamic parameters in myocardial infarction-induced cardiac failure in rats (2000)
    Springer
    Virchows Archiv 436 (2000), S. 147-157 
    Details
    ISSN: 1432-2307
    Keywords: Key words T-type calcium channel blockade ; Mibefradil ; Myocardial infarction ; Cardiac remodeling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dtmax) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dtmax were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dtmax were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008215
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    Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal (2000)
    Springer
    Psychopharmacology 149 (2000), S. 170-175 
    Details
    ISSN: 1432-2072
    Keywords: Key words  m-Chlorophenylpiperazine ; Drug discrimination ; Ethanol withdrawal ; Anxiety ; 17β-estradiol ; Sex difference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900353
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    The dynamic infusion test in rats (2000)
    Springer
    Child's nervous system 16 (2000), S. 451-456 
    Details
    ISSN: 1433-0350
    Keywords: Keywords Intracranial pressure ; CSF dynamics ; Infusion test ; Rat ; H-Tx rat ; Outflow resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although the hydrocephalic H-Tx rat is a widely used model, data on the cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or – as the pressure volume index (PVI) – not available. We used hydrocephalic and nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited hydrocephalus, for the evaluation of such data. In addition, a new, simple mathematical algorithm (”dynamic infusion test”), which has not formerly been used in animal experiments, was used as a pathophysiological model of CSF dynamics. Compared with classical methods for evaluation of these data, the dynamic infusion test gives a deeper insight into the relation between ICP and CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic rats was at least twice that in nonhydrocephalic rats. The PVI measured was similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than the values reported in the literature. This may be attributable to the fact that the classically used bolus test, in contrast to the ”dynamic infusion test”, is representative only for the CSF compartment which is directly exposed to the bolus application.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007290
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    Sensitization of amphetamine-induced wheel running suppression in rats: dose and context factors (2000)
    Springer
    Psychopharmacology 151 (2000), S. 219-225 
    Details
    ISSN: 1432-2072
    Keywords: Keywords Amphetamine ; Wheel running ; Behavioral sensitization ; Pharmacological sensitization ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study explored whether repeated injections of amphetamine (AMP), which increase general locomotion, also increase acute wheel running, a highly structured, rewarding, motor behavior not correlated with other locomotor activities. Objectives: The experiments determine how 1–5 mg/kg d-AMP affects wheel running and see if, over repeated injections, the AMP effects show context specific sensitization. Methods: In experiment 1, 2 mg/kg AMP or saline (SAL) was injected on days 1, 3, 6, 8, and 10 to male Sprague-Dawley rats with either limited or no wheel experience. 20 min after the injection animals were tested in an open field for 5 min and then in a running wheel for 1 h. Rats were injected with SAL or AMP on the days following testing. On days 13 and 15, animals were tested for conditioning (following SAL) and sensitization (following AMP). In experiment 2, the effects on wheel running of repeated 1, 2, or 5 mg/kg AMP were tested. Results: In experiment 1, AMP (2 mg/kg) elevated open field ambulation but suppressed wheel running. Limited wheel experience potentiated the AMP-induced suppression. At test, the suppression of running was found to be context specific. In experiment 2, 1 mg/kg did not affect running, while 2 and 5 mg/kg resulted in dose-dependent running suppression. Acquisition and test AMP dose both influenced the running suppression at test; context had a marginal influence. Conclusions: The degree of running suppression induced by repeated AMP is determined by both psychological (the injection context) and pharmacological (the acquisition dose) factors. This AMP-induced running suppression is consistent with the sensitization of stereotyped behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000446
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    Discriminative stimulus effects of two doses of fentanyl in rats: pharmacological selectivity and effect of training dose on agonist and antagonist effects of mu opioids (2000)
    Springer
    Psychopharmacology 148 (2000), S. 136-145 
    Details
    ISSN: 1432-2072
    Keywords: Key words Fentanyl ; mu opioids ; Drug discrimination ; Training dose ; pA2 analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Discriminative stimulus effects of mu opioids vary systematically as a function of training dose. Differences among training doses may arise from multiple mechanisms. Objectives: In vivo apparent pA2 analyses were used to examine the contributions of opioid mechanisms to stimulus control by low and high training doses of the mu opioid fentanyl. Methods: Saline and one of two doses of fentanyl, administered s.c., were established as discriminative stimuli in two groups of rats (low training dose group: 0.01 mg/kg; high training dose group: 0.04 mg/kg). Generalization tests and in vivo apparent pA2 analyses were used to evaluate receptor mechanisms of stimulus control. Results: Fentanyl, etonitazene, methadone, and morphine evoked full fentanyl generalization in both groups but were more potent in the low-dose group. Spiradoline and d-amphetamine did not evoke generalization in either group. Naltrexone antagonized stimulus and rate-altering effects of fentanyl in both groups, with apparent pA2 values of 7.6 in the low-dose group and 7.5 in the high-dose group. Nalbuphine and nalorphine evoked full generalization in the low-dose group but less than 40% generalization in the high-dose group. In the high-dose group, nalbuphine and nalorphine antagonized the stimulus and rate-altering effects of fentanyl with apparent pA2 values of 5.3 and 6.1, respectively, demonstrating lower efficacy mu actions. Conclusions: Changes in fentanyl training dose preserved the mu opioid selectivity of stimulus control but altered the intensity of the transduced mu opioid stimulus required for generalization. These differences in intensity of the fentanyl stimulus determined whether low efficacy mu opioids would evoke or antagonize fentanyl generalization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050035
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    Discriminative stimulus properties of alprazolam (2000)
    Springer
    Psychopharmacology 148 (2000), S. 146-152 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alprazolam ; Drug discrimination ; Benzodiazepines ; Antidepressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The triazolobenzodiazepine alprazolam has a unique clinical profile compared to most other benzodiazepines (e.g. diazepam, chlordiazepoxide), in that it is used to treat panic disorder and is effective in depression, two disorders that are usually treated with anti-depressants. Previous drug discrimination studies suggested that alprazolam has stimulus properties in common with antidepressants. Objective: In the present study, the discriminative stimulus properties of alprazolam were investigated to test more conclusively the role of benzodiazepine receptors and whether alprazolam has stimulus properties in common with antidepressants. Methods: Male Wistar rats (n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and vehicle in an operant two-lever drug discrimination procedure under a tandem VI40”-FR10 schedule of reinforcement. Generalization and antagonism tests were carried out under 2 min extinction. Results: In generalization tests, a number of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the barbiturate pentobarbital substituted completely, while zolpidem and abecarnil substituted partially for alprazolam. In contrast, no significant degree of generalization to the antidepressants imipramine and fluvoxamine and the putative antidepressants buspirone and flesinoxan was found. In antagonism studies alprazolam could be antagonized (almost) completely by flumazenil, partially by pentylenetetrazole, but not by methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), N-methyl-β-carboline-3-carboxamide (FG-7142) and picrotoxin. Conclusions: These results show that the discriminative stimulus properties of alprazolam are mediated by benzodiazepine receptors and that the finding that antidepressants share discriminative stimulus effects with alprazolam may have limited generality.
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    URL: http://dx.doi.org/10.1007/s002130050036
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    Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 209-216 
    Details
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Drug-discrimination ; Dopamine ; Cocaine ; GBR-12909 ; Nomifensine ; Bupropion ; Chloro-PB ; Chloro-APB ; NPA ; 7-OH-DPAT ; SCH-23390 ; Spiperone ; cis-Flupenthixol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Dopamine plays a major role in the behavioral effects of methamphetamine. Objective: In the present experiments, the effects of different dopaminergic agonists, antagonists, and uptake inhibitors were evaluated in rats discriminating methamphetamine from saline. Methods: In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food delivery, the ability of various dopaminergic agonists and uptake inhibitors to substitute for methamphetamine was evaluated. Subsequently, the ability of various dopaminergic antagonists to block the discriminative-stimulus effects of the training dose of methamphetamine was tested. Results: The dopamine-uptake inhibitors cocaine (10.0 mg/kg), nomifensine (3.0 mg/kg), GBR-12909 (18.0 mg/kg), and bupropion (30.0 mg/kg) fully substituted for the 1.0 mg/kg training dose of methamphetamine. Chloro-APB (SKF-82958), a full agonist at D1 dopamine receptors, produced about 85% methamphetamine-appropriate responding, but the dose required (0.18 mg/kg) markedly decreased rates of responding. Chloro-PB (SKF-81297), another agonist at D1 receptors with a lower intrinsic activity than Chloro-APB, produced only partial generalization (maximum about 55%) at a dose of 1.0 mg/kg. Full substitution for the training dose of methamphetamine was observed with 0.03 mg/kg of the D2 agonist NPA and 0.56 mg/kg of the D3/D2 agonist 7-OH-DPAT. Both NPA and 7-OH-DPAT markedly decreased rates of responding at these doses. The D1 antagonist SCH-23390 (0.056 mg/kg), the D2 antagonist spiperone (0.18 mg/kg), and the mixed D1,D2 antagonist cis-flupenthixol (0.56 mg/kg) all completely blocked the discriminative-stimulus actions of the training dose of methamphetamine. Conclusions: The present findings in rats support previous research findings in other species indicating a major role of dopamine in the discriminative-stimulus effects of methamphetamine. These findings further indicate involvement of dopamine uptake sites as well as D1 and D2 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050044
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    Effects of the competitive nicotinic antagonist erysodine on behavior occasioned or maintained by nicotine: comparison with mecamylamine (2000)
    Springer
    Psychopharmacology 148 (2000), S. 234-242 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Drug discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The cellular effects of nicotine underlying its addictive liability are thought to be mediated by neuronal nicotinic receptors (nACHRs) in the central nervous system. It is believed that densely expressed β2-containing nACHRs in the central nervous system are responsible for these actions, but few data are available that can directly assess subtype mediation of nicotine’s acute subjective and reinforcing effects. Objective: The present study compared the effects of the competitive nACHR antagonist erysodine and the noncompetitive antagonist mecamylamine in rats trained to discriminate or self-administer nicotine. Methods: Adult male rats were trained to disciminate 0.4-mg/kg injections of nicotine from vehicle in a two-lever procedure of food-maintained behavior, or to self-administer 0.03-mg/kg injections of nicotine under fixed-ratio 5 or progressive-ratio schedules of reinforcement. Additional rats were trained under a food-maintained procedure of lever pressing. Results: Erysodine (0.3–10 mg/kg) and mecamylamine (0.1–1.0 mg/kg) blocked nicotine discrimination, although only erysodine produced the rightward shift that would be predicted of a competitive antagonist. Erysodine (0.32–32 mg/kg) and mecamylamine (0.32–3.2 mg/kg) also selectively reduced nicotine self-administration on a fixed-ratio schedule and lowered break points on a progressive-ratio schedule. Conclusions: Based on the known affinity of erysodine for α4β2 nACHRs and its selectivity relative to α7 and α1β1γδ receptors, the present data support a critical role of β2-containing nACHR constructs in the discriminative and reinforcing actions of nicotine.
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    URL: http://dx.doi.org/10.1007/s002130050047
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    The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 224-233 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Olanzapine ; Clozapine ; Chlorpromazine ; Haloperidol ; Thioridazine ; Raclopride ; Risperidone ; Scopolamine ; Ritanserin ; Atypical antipsychotic ; Neuroleptic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Analysis of the preclinical behavioral effects of atypical antipsychotic agents will provide a better understanding of how they differ from typical antipsychotics and aid in the development of future atypical antipsychotic drugs. Objectives: The present study was designed to provide information about the discriminative stimulus properties of the atypical antipsychotic olanzapine. Methods: Rats were trained to discriminate the atypical antipsychotic olanzapine (either 0.5 mg/kg OLZ or 0.25 mg/kg OLZ, i.p.) from vehicle in a two- lever drug discrimination procedure. The atypical antipsychotic clozapine fully substituted for olanzapine in both the 0.5-mg/kg OLZ group (99.3% drug lever responding [DLR]) and the 0.25-mg/kg OLZ group (99.9% DLR). The typical antipsychotic chlorpromazine also substituted for olanzapine in both the 0.5-mg/kg OLZ group (87.5% DLR) and in the 0.25-mg/kg OLZ group (98.9% DLR); whereas, haloperidol displayed partial substitution for olanzapine in the 0.5-mg/kg OLZ group (56.1% DLR) and in the 0.25-mg/kg OLZ group (76.4% DLR). The 5.0-mg/kg dose of thioridazine produced olanzapine-appropriate responding in the 0.5-mg/kg OLZ group (99.6% DLR), but only partial substitution was seen with the 0.25-mg/kg OLZ training dose (64.0% DLR). The atypical antipsychotics raclopride (53.9% DLR) and risperidone (60.1% DLR) displayed only partial substitution in the 0.5-mg/kg OLZ group. Both the muscarinic cholinergic antagonist scopolamine (90.0% DLR) and the 5-HT2A/2C serotonergic antagonist ritanserin (86.0% DLR) fully substituted for olanzapine in the 0.5-mg/kg OLZ group. Conclusions: In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine’s discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050046
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    Electronic Resource
    The role of nicotinic and muscarinic acetylcholine receptors in attention (2000)
    Springer
    Psychopharmacology 148 (2000), S. 243-250 
    Details
    ISSN: 1432-2072
    Keywords: Key words Attention ; Scopolamine ; Mecamylamine ; Oxotremorine ; Physostigmine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study tried to determine the relative roles of muscarinic and nicotinic cholinergic receptors in attentional processing. Methods: The effects of cholinoceptor agonists and antagonists, and of an anticholinesterase, were studied on performance of rats in a five-choice serial reaction time task. Results: Scopolamine (0.1 mg/kg) and mecamylamine (5.0 mg/kg) produced deficits in accuracy and reaction time, respectively. This may suggest a differential role for the two types of cholinoceptors in information processing. Combinations of sub-threshold doses of scopolamine (0.01–0.03 mg/kg) and mecamylamine (0.5–1.6 mg/kg), which alone did not affect accuracy or reaction time, did not produce significant deficits in attention. However, the pattern of effects after combined treatment suggested that the differential deficits seen with these drugs alone remained. The anticholinesterase physostigmine (0.1 mg/kg) and the non- selective muscarinic agonist oxotremorine (0.03 mg/kg) induced severe behavioural disruption at doses that appeared to be relatively well tolerated in previous studies; this precluded the derivation of accuracy and response time data at these doses. At lower doses, neither physostigmine (0.05 mg/kg) nor oxotremorine (0.003 mg/kg) significantly affected any performance measure; this may reflect the ability of both drugs to indirectly or directly activate presynaptic muscarinic receptors that inhibit acetylcholine release, respectively. Conclusions: Both muscarinic and nicotinic cholinoceptors may be important in attention but they may serve different roles in information processing; this hypothesis could be tested using tasks that place different emphasis on different stages of information processing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050048
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    Behavioral tolerance to the force differentiation effects of diazepam and midazolam in rats (2000)
    Springer
    Psychopharmacology 148 (2000), S. 327-335 
    Details
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Operant ; Force ; Tolerance ; Chronic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Several benzodiazepines (BZs) have been shown to increase the peak force of operant responses at doses that increased, decreased, or had no effect on response rate, suggesting that operant response force may be a sensitive index of BZs’ effects rather than solely a correlate of rate-dependent effects. In addition, contingent tolerance to the rate-dependent effects of BZs has been reported, but the degree of contingent tolerance that develops when the critical variable of the task is force of the response has not been explored. Objectives: These experiments examined the effects of acute and repeated oral administration of diazepam (DZ) and midazolam (MZ) on a force-differentiation task to explore the importance of task requirements on the development of contingent tolerance. Methods: Two groups of rats were trained to press a force-sensing operandum, and responses having peak forces falling within fixed lower and upper limits [low force (8–10 g) or high force (40–50 g)] were reinforced with water. Acute effects of the oral administration of DZ (0.3, 1.0, 3.0, 10.0, 30.0 mg/kg) and MZ (same doses) were determined for the discriminated-force task before and after a repeated-administration procedure. Results: When administered acutely, both drugs increased the peak force of responses in a dose-related manner and concomitantly reduced the proportion of reinforced responses, with MZ exhibiting greater potency. For the next 36 days, one group received drug before experimental sessions and the other group received drug after the experimental session. A second dose–effect determination demonstrated that rats chronically dosed with DZ or MZ pre-session displayed more contingent tolerance to alterations in peak force than rats that had received 36 drug injections post- session, where there was no opportunity to practice the force-discrimination response while under the drug state. Conclusions: These results suggest that perceptual motor difficulty of the task rather than effort may be an important variable in predicting the degree of contingent tolerance that develops. Additionally, these results suggest that both behavioral and pharmacological mechanisms are involved in the development of drug tolerance to the BZs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050059
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  • 48
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    Diazepam-like effects of a fish protein hydrolysate (Gabolysat PC60) on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenal activity (2000)
    Springer
    Psychopharmacology 149 (2000), S. 34-40 
    Details
    ISSN: 1432-2072
    Keywords: Key words ACTH ; Corticosterone ; GABA ; Noradrenaline ; Adrenaline ; Stress ; Rat ; Diazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Gabolysat PC60 is a fish protein hydrolysate with anxiolytic properties commonly used as a nutritional supplement. Objective: The diazepam-like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. Methods: The activity of the pituitary-adrenal axis, measured by plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (B) of the sympathoadrenal complex, measured by circulating levels of noradrenaline (NA) and adrenaline (A), and the gamma aminobutyric acid (GABA) content in the hippocampus and the hypothalamus were investigated in male rats which received daily, by an intragastric feeding tube, for 5 days running either diazepam (1 mg/kg) or PC60 (300 or 1200 mg/kg). Controls received only solvent (carboxymethylcellulose 1%). Six hours after the last force-feeding, the rats were subjected to 3 min ether inhalation or 30 min restraint and killed by decapitation 30 min after ether stress or at the end of restraint. Results: Baseline plasma levels of ACTH, B, NA and A were not affected by either diazepam or PC60. Both ether- and restraint-induced release of ACTH, but not B, were similarly and drastically reduced by diazepam and PC60 (1200 mg/kg). Both diazepam and PC60 (1200 mg/kg) deleted restraint-induced NA and A increases. Both treatments also reduced the ether-induced rise of A. Basal levels of GABA were significantly increased in both the hippocampus and the hypothalamus in PC60-treated rats and only in the hippocampus in diazepam-treated ones. In controls, ether inhalation as well as restraint increased GABA content of these two brain structures. In contrast, such stress procedures performed in PC60-treated rats reduced GABA content slightly in the hippocampus but significantly in the hypothalamus. In diazepam-treated rats, GABA content of the hypothalamus was unaffected by stresses but that of the hippocampus was slightly decreased. Conclusions: Present data suggest diazepam-like effects of PC60 on stress responsiveness of the rat pituitary adrenal axis and the sympathoadrenal activity as well as GABA content of the hippocampus and the hypothalamus under resting and stress conditions. These effects of PC60 agree with anxiolytic properties of this nutritional supplement, previously reported in both rats and humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900338
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    The 5-HT1A receptor agonist 8-OH-DPAT reduces rats’ accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT1A receptors (2000)
    Springer
    Psychopharmacology 149 (2000), S. 259-268 
    Details
    ISSN: 1432-2072
    Keywords: Key words 8-OH-DPAT ; WAY 100635 ; 5 ; 7-Dihydroxytryptamine ; Attention ; Impulsivity ; Pre- and postsynaptic 5-HT1A receptor ; Dorsal raphe ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Whilst several studies have investigated the role of serotonergic receptor subtypes in learning and memory, relatively few studies have examined their role in attentional processes. Objective: The present study investigated the role of pre- and postsynaptic 5-HT1A receptors on rats’ attentional performance in the five-choice serial reaction time task (5-CSRT). Methods: Hungry rats were trained in the 5-CSRT task to detect brief (0.5 s) flashes of light presented randomly in one of five locations with a fixed intertrial interval of 5 s paced by the rat. We studied the effects of 8-OH-DPAT, a 5-HT1A receptor agonist, at various subcutaneous (SC) doses (10–100 µg/kg) on measures of rats’ discriminative accuracy (the index of attentional functioning) and various behavioural indices of response control and motivation. Manipulations of basic task parameters, intracerebroventricular (ICV) injections of 5,7-dihydroxytryptamine (5,7-DHT) to deplete forebrain 5-HT and treatments with a selective 5-HT1A receptor antagonist WAY 100635 were made in order to determine the behavioural and neural specificity of the effects of 8-OH-DPAT. Results: A dose of 100 µg/kg, but not lower doses, significantly reduced choice accuracy and increased errors of omission, latencies to respond correctly and to collect food reward and premature responses. All these effects were completely blocked by WAY 100635, injected SC 5 min before 8-OH-DPAT at doses from 10–100 µg/kg. WAY 100635 by itself had no effect in the task. Dimming the visual stimuli to one-third of the usual brightness did not modify the effect of 8-OH-DPAT on choice accuracy. Prolonging the stimuli from 0.5 to 1.0 s reversed 8-OH-DPAT’s effect on choice accuracy but did not modify the other effects on rats’ performance. An ICV injection of 150 µg 5,7-DHT, which depleted forebrain serotonin by 90%, reversed 8-OH-DPAT’s effect on choice accuracy but did not modify the effects on errors of omission and latency to make correct responses. Similar effects were found by infusing 1.0 µg/0.5 µl WAY 100635 in the dorsal raphe 5 min before 8-OH-DPAT. 8-OH-DPAT increased the latency to collect the reinforcement; this effect was attenuated by ICV 5,7-DHT and completely antagonized by WAY 100635 in the dorsal raphe. Rats treated with 5,7-DHT or 8-OH-DPAT showed more premature responses and these effects were markedly reduced by the combined treatment. Conclusions: The results suggest that stimulation of presynaptic 5-HT1A receptors is involved in the ability of 8-OH-DPAT to cause attentional dysfunction and enhance impulsivity while slowing of responding and increase in errors of omission mainly depend on stimulation of postsynaptic 5-HT1A receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900368
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    Effects of cytomegalovirus infection and prolonged cold ischemia on chronic rejection of rat renal allografts (2000)
    Springer
    Transplant international 13 (2000), S. 54-63 
    Details
    ISSN: 1432-2277
    Keywords: Key words Kidney transplantation ; Rat ; Chronic rejection ; Cytomegalovirus ; Adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that both cytomegalovirus (CMV) infection and prolonged cold ischemia of the allograft (CI) are associated with chronic rejection of renal transplants. The purpose of this study is to investigate the effect of CMV infection, of CI and of the combination of both, on the progression of chronic rejection, and to obtain a more detailed insight in their effects on the expression of adhesion molecules. Therefore, a rat transplantation model was used. Lewis recipients of renal allografts (with and without CI) from MHC-incompatible Brown Norway rats were inoculated with rat CMV or left uninfected. CMV infection alone resulted in an increased influx of CD4+ cells and macrophages early after infection, and in an increase in glomerular sclerosis and intima proliferation. CI caused an increase in infiltrating NK cells and an effect on intimal proliferation, glomerular sclerosis, and tubular atrophy. When CMV infection and CI were combined, an additive effect could be measured. This was however not the case for the function of the kidney. The creatinin showed a synergistic effect of the two influencing factors. Due to the CMV infection, an increase in CD49 d cells was detected. CI resulted in an increase in CD18 cells and an increase in the expression of CD62P on vessels, and CD54 and CD44 on tubules. When CMV infection and CI were combined, all the effects caused by CMV and CI alone were present in an additional way.¶The results of the present study suggest that special attention should be paid to the recipient of an ischemically injured graft when either the donor or the recipient is CMV-infected. The patterns seen in histology, the infiltration of leukocytes and the expression of adhesion molecules, suggest that CI and CMV infection both have an effect on rejection, but act by different mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050009
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    Effect of anti-CD4 monoclonal antibody administration on rat small bowel allograft survival and circulating leukocyte populations (2000)
    Springer
    Transplant international 13 (2000), S. 211-217 
    Details
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Monoclonal antibody ; Rat ; Rejection ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effect of an anti-rat CD4 monoclonal antibody (OX38) on heterotopic small bowel allograft rejection. Fully allogeneic small bowel transplants were performed in the PVG-to-DA-rat strain combination. Animals received either i) short course (days –1, 0 and 1) of 1 mg/kg per day OX38, ii) short course of 5 mg/kg per day or iii) extended course (days –2, –1, 0, 1, 2 and twice weekly thereafter) of 1 mg/kg per day. Both the high dose (13 days) and extended low-dose (12 days) courses prolonged graft survival compared to untreated control animals (7 days). The low-dose, short-course treatment had no effect. Similar regimens were given to animals that did not receive transplants and in which peripheral blood CD4+ cell counts fell to between 20 and 55 % of pretreatment levels and 20–30 % of binding sites were blocked. In summary, anti-CD4 monoclonal antibody therapy delayed rejection of rat small bowel allografts; however, long-term survival was not achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050689
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    Regional Spinal Cord Blood Flow and Energy Metabolism in Rats after Laminectomy and Acute Compression Injury (2000)
    Springer
    European journal of trauma 26 (2000), S. 122-130 
    Details
    ISSN: 1615-3146
    Keywords: Key Words Spinal cord compression ; Autoradiography ; Blood flow ; ATP ; Glucose ; Lactate ; Bioluminescence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many data are available concerning spinal cord blood flow (SCBF) and metabolism on various models and timing after spinal cord injury, however, detailed information on their exact relationship in the same injury model is lacking. This relationship is a crucial factor in the understanding of the pathophysiology of spinal cord trauma. Rats were subjected to lumbar laminectomy or lumbar spinal cord compression trauma. 3 hours later, changes in SCBF were evaluated autoradiographically and changes in ATP, glucose and lactate levels were analyzed using substrate-specific bioluminescence techniques. Measurements were performed at the lesion site (segment L4), adjacent segments (L3 and L5) and at remote thoracic segments (Th8 to Th9). Laminectomy alone did not change SCBF, both in thoracic and lumbar segments. In contrast, ATP levels were significantly reduced and lactate levels were increased at the lesion site and in adjacent lumbar segments at 3 hours after laminectomy, whereas glucose levels were not significantly changed. In animal subjected to additional compression trauma, SCBF was significantly reduced in segments L3, L4 and L5 paralleled by a significant ATP reduction and lactate increase. Glucose levels did not differ significantly from controls 3 hours after compression injury. This metabolic profile was also reflected in the remote thoracic segments. In contrast, SCBF was not reduced in thoracic segments of traumatized animals. The observation that ATP was already significantly reduced and lactate increased in laminectomized segments and in remote thoracic regions after trauma signals that metabolic changes are sensitive indicators to spinal stress. The fact that posttraumatic metabolic profile differs from the pattern of hemodynamic and metabolic changes induced by ischemia, suggests posttraumatic mediators may be involved in the different regulation of the energy producing machinery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000680050010
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    Mechanomyograms recorded during evoked contractions of single motor units in the rat medial gastrocnemius muscle (2000)
    Springer
    European journal of applied physiology 83 (2000), S. 310-319 
    Details
    ISSN: 1439-6327
    Keywords: Key words Motor unit ; Mechanomyography ; Evoked contraction ; Medial gastrocnemius muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acoustic phenomena accompanying contractions of single motor units (MUs) have previously received little attention. Therefore, in the present study, the mechanomyographic (MMG) signals during evoked contractions of single MUs have been recorded from the medial gastrocnemius muscle of the rat. A piezoelectric transducer immersed in a paraffin-oil pool was used for the measurement of these signals. Muscle fibre action potentials, tension and MMG were recorded in parallel during twitch (the weakest) and fused tetanic (the strongest) MU contractions. It was observed that the onset of the MMG signals was coincident with the beginning of the increase in tension for both the twitch and tetanus. Weaker MMG signals than those accompanying the beginning of the first phase of the fused tetanus were seen during the beginning of the relaxation after tetanic contraction. During contraction and relaxation, MMG signals were characterised by the reverse-direction of the first extreme phase, positive and negative, respectively. No MMG signals were observed when the tension was constant during the fused tetanus. The amplitude of MMG signals was correlated with both the tension increase and the velocity of tension increase during both the twitch and the fused tetanus. The strongest MUs (fast fatiguable) generated MMG signals of the highest amplitude. MMG signals were not detected for some of the weakest slow MUs (with tension increases of ≤2 mN). These results indicate a strong correlation between the MMG and the change of tension. Therefore, we believe that MMG signals are generated by muscle deformation that occurs during the contraction of MU muscle fibres. We conclude that the number of active muscle fibres, their topography, and their localisation in relation to the muscle surface (which is variable for different types of MUs) influence these MMG phenomena.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210000261
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    Modulation of Paired-Pulse Responses in the Dentate Gyrus: Effects of Normal Maturation and Vigilance State (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 128-134 
    Details
    ISSN: 1573-9686
    Keywords: Hippocampus ; Vigilance states ; Paired-pulse ; Dentate gyrus ; Dentate granule cells ; Evoked response ; Rat ; In vivo studies ; Perforant path ; Maturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract This study examined the effect of normal development and vigilance state on the modulation of dentate granule cell activity in the freely moving rat at 15, 30, and 90 days of age across three vigilance states: quiet waking, slow-wave sleep, and rapid eye movement sleep. Using paired-pulse stimulation, the paired-pulse index (PPI) was obtained for the dentate evoked field potentials elicited by the stimulation of the medial perforant path. Although significant differences in PPI values were observed during development, no significant vigilance state related changes were obtained. Preweaning infant rats, i.e., 15-day old, exhibited significantly less early (interpulse intervals, IPI= 20–50 ms) and late (IPI = 300–1000 ms) inhibition, and less facilitation (IPI = 50–150 ms) when compared to the 90-day old adult rats during all three vigilance states. PPI values obtained from the 30-day old group fell intermediate between the 15- and 90-day old animals. These changes in PPI values provide a quantitative measure of changes in the modulation of dentate granule cell excitability during normal maturation. They can now can be used to evaluate the impact of various insults, such as prenatal protein malnutrition or neonatal stress, on hippocampal development. © 2000 Biomedical Engineering Society. PAC00: 8717Nn, 8719La, 8719Nn
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.261
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    Left Ventricular Contractility is Impaired Following Myocardial Infarction in the Pig and Rat: Assessment by the End Systolic Pressure–Volume Relation Using a Single-Beat Estimation Technique and Cine Magnetic Resonance Imaging (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 484-494 
    Details
    ISSN: 1573-9686
    Keywords: Heart ; Left ventricle ; LV contractility ; ESPVR ; Pig ; Rat ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The end systolic pressure–volume relation (ESPVR) has been shown to be a relatively load independent measure of left ventricular (LV) contractility. Recently, several single-beat ESPVR computation methods have been developed, enabling the quantification of LV contractility without the need to alter vascular loading conditions on the heart. Using a single-beat ESPVR method, which has been validated previously in humans and assumes that normalized elastance is constant between individuals of a species, we studied the effects of myocardial infarction on LV contractility in two species, the rat and the pig. In our studies, LV pressure was acquired invasively and LV volume determined noninvasively with magnetic resonance imaging, at one week postinfarction in pigs and at 12 weeks postinfarction in rats. Normalized systolic elastance curves in both animal species were not statistically different from that of humans. Also, the slope of the ESPVR $$\left( {E_{es} } \right)$$ decreased significantly following infarction in both species, while the volume-axis intercept $$\left( {V_0 } \right)$$ was unaffected. These results indicate that a single-beat ESPVR method can be used to measure the inotropic response of the heart to myocardial infarction, and that the basis for this method (i.e., constant normalized elastance) is applicable to a variety of mammalian species. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8761Lh, 8719Hh, 8719Rr, 8719Ff
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    URL: http://dx.doi.org/10.1114/1.289
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    Quantifying Coevolution of Nonstationary Biomedical Signals Using Time-Varying Phase Spectra (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 1101-1115 
    Details
    ISSN: 1573-9686
    Keywords: Time–frequency analysis ; Coherence ; Cross correlation ; Nonstationary persistent signals ; Central pattern generator ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We present a novel time-varying phase spectrum (TVPS) method to quantify the dynamics of coevolution of two persistent nonstationary coupled signals. Based on the TVPS, an instantaneous intersignal phase shift is defined within the primary frequency range in which the two signals are highly correlated. The TVPS is estimated using a fixed-window method or an adaptive-window method. In the latter method, the window length changes dynamically and automatically as a function of change in frequency of the signals. The effects of altering window types and lengths on the accuracy of the estimation of the primary phase shift is assessed by analyzing synthesized linear chirp signals with decaying amplitude and constant relative phase shift or decaying amplitude and changing relative phase shifts. The methods developed are also used for determining the evolution of the primary phase shift among ventral root activities during fictive locomotion in an in vitro rat spinal cord preparation. The analyses indicate that the TVPS method in conjunction with the determination of the primary frequency range, allows determination of both the evolution of the coupling strength and the evolution of the phase shift between two persistent nonstationary rhythmic signals in the joint time–frequency domain. An adaptive window reduces the estimation bias and the estimation variability. © 2000 Biomedical Engineering Society. PAC00: 0230-f, 8780Tq
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.1313775
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    Halothane anesthesia decreases the extracellular level of dopamine in rat striatum: a microdialysis study in vivo (2000)
    Springer
    Journal of anesthesia 14 (2000), S. 82-90 
    Details
    ISSN: 1438-8359
    Keywords: Key words: Halothane ; Dopamine release ; Dopamine uptake ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose. In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. Methods. Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. Results. General anesthesia with halothane alone de-creased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. Conclusion. These results suggest that halothane po-tently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005400050072
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    c-Fos Expression by Dopaminergic Receptor Activation in Rat Hippocampal Neurons (2000)
    Springer
    Molecules and cells 10 (2000), S. 546-551 
    Details
    ISSN: 0219-1032
    Keywords: c-Fos ; Dopamine ; D1 ; Hippocampus ; Rat ; Synaptic Plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract While dopamine is likely to modulate hippocampal synaptic plasticity, there has been little information about how dopamine affects synaptic transmission in the hippocampus. The expression of IEGs including c-fos has been associated with late phase LTP in the CA1 region of the hippocampus. The induction of c-fos by dopaminergic receptor activation in the rat hippocampus was investigated by using semiquantitative RT-PCR and immuno-cytochemistry. The hippocampal slices which were not treated with dopamine showed little expression of c-fos mRNA. However, the induction of c-fos mRNA was detected as early as 5 min after dopamine treatment, peaked at 60 min, and remained elevated 5 h after treatment. Temporal profiles of increases in c-fos mRNA by R(+)-SKF-38393 (50 μM) and forskolin (50 μM) were similar to that of dopamine. An increase in [cAMP] was observed in dopamine-, SKF-, or forskolin-treated hippocampal slices. By immunocytochemical studies, control hippocampal cells showed little expression of c-Fos immunoreactivity. However, when cells were treated with dopamine, an increase in the expression of c-Fos immunoreactivity was observed after treatment for 2 h. The treatment of hippocampal neurons with R(+)-SKF38393 (50 μM) or forskolin (50 μM) also induced a significant increase in c-Fos expression. These results indicate that the dopamine D1 receptor-mediated cAMP dependant pathway is associated with the expression of c-Fos in the hippocampal neurons. These data are consistent with the possible role of endogenous dopamine on synaptic plasticity via the regulation of gene expression. Furthermore, these results imply that dopamine might control the process of memory storage in the hippocampus through gene expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s10059-000-0546-y
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  • 59
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    Electronic Resource
    Detection and analysis of gastrointestinal sounds in normal and small bowel obstructed rats (2000)
    Springer
    Medical & biological engineering & computing 38 (2000), S. 42-48 
    Details
    ISSN: 1741-0444
    Keywords: Bowel sounds ; Rat ; Motility ; Body acoustics ; Signal detection ; Signal characterisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This study is aimed at detecting gastrointestinal sounds (GIS) and correlating their characteristics with gastrointestinal (GI) conditions. The central hypotheses are that GIS generation depends on the motility patterns and the mechanical properties of the gut, and that changes in those result in measurable differences in GIS. An animal model which included both healthy rats and those with small bowel obstruction (SBO) was developed. The acoustic bursts, of GIS were detected by amplitude thresholding the signal envelope. Three methods of envelope estimation were proposed and evaluated. Envelope estimation using a Hilbert transform was found to produce the best results in the current application. The duration and dominant frequency of each detected GIS event was estimated and clear differences between healthy and diseased rats were discovered. In the control state, GIS events were found to consistently be of relatively short duration (3–65ms). Although the majority of events in the SBO state had similar short duration, infrequent longer events were also detected and appeared to be pathognomonic. Long duration events (〉100 ms) occurred in each of seven obstructed, but in none of 14 non-obstructed, cases (p〈0.001). It is concluded that GIS analysis may prove useful in the non-invasive, rapid, and accurate diagnosis of SBO.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02344687
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  • 60
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    Electronic Resource
    The ponto-cerebellar projection in the rat: Differential projections to sublobules of the uvula (1980)
    Springer
    Experimental brain research 38 (1980), S. 11-17 
    Details
    ISSN: 1432-1106
    Keywords: Cerebellum ; Pontine nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microinjections of horseradish peroxidase (HRP) were made in different sublobules of the uvula (lobule IX, a, b, and c of Larsell, 1952) of the cerebellar cortex in the rat. These injections resulted in retrograde labeling of cells located in the pontine nuclei. Sublobule IXa receives a predominant input from a single column of cells situated in a dorsointermediate position in the caudal pontine nuclei. Sublobules IXb and IXc receive a pontine projection from two different columns of cells, one medial and one lateral. The location of the labeled cells in the lateral part of the caudal pons suggests a topographic projection to the subdivisions of the uvula. Sublobule IXa receives a projection from a distinct dorsointermediate region and sublobule IXb and IXc receive a projection from partially overlapping ventral regions. The cells of origin in the medial pons are organized such that more dorsally located cells project to sublobule IXc and ventrally located cells project to sublobule IXb with extensive overlap. These differential patterns of projections to the sublobules of the uvula along with other data in the literature suggest that sublobule IXa may be involved with different functional correlates than sublobules IXb and IXc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00237925
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  • 61
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    Cytometric investigations in histochemically identified neurons — Changes of fluorescence intensities and nuclear diameters in dopamine neurons of the arcuate nucleus in the cycling rat (1980)
    Springer
    Experimental brain research 38 (1980), S. 293-298 
    Details
    ISSN: 1432-1106
    Keywords: Rat ; Estrous cycle ; Hypothalamic arcuate nucleus ; Dopamine perikarya ; Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative formaldehyde-induced fluorescence intensities and the diameter of cell nuclei of fluorescent perikarya of the arcuate nucleus were recorded in serial cross-sectioned hypothalamic arcuate nuclei of regularly cycling rats (5 estrous and 4 proestrous animals). Stress-induced changes of cytometric parameters were avoided by preadaptation of animals to handling procedures. Dopamine neurons in a 75 μm thick periventricular layer of the arcuate nucleus exhibited significantly smaller nerve cell nuclei and significantly reduced relative fluorescence intensities in proestrous rats. Both of these cytometric parameters indicate a decrease in the activity of periventricular dopamine neurons of the arcuate nucleus. The reported findings might support the hypothesis that dopamine inhibits the release of LH-RH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236648
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  • 62
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    Stimulation-dependent changes in synaptic effects on unit activity of medial preoptic nucleus neurones in rats (1980)
    Springer
    Experimental brain research 39 (1980), S. 121-124 
    Details
    ISSN: 1432-1106
    Keywords: Amygdala ; Medial preoptic nucleus ; Median eminence ; Rat ; Synaptic plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Stimulation-dependent changes in synaptic effects were observed in medial preoptic nucleus neurones during stimulation of the amygdala or pyriform cortex in anaesthetized female rats. The changes occurred after 35–240 triple pulse stimuli repeated at 0.89 Hz. Median eminence stimulation did not produce any synaptic change. These data show the existence of synaptic plasticity in the neural pathway from the amygdala and pyriform cortex to the medial preoptic nucleus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00237076
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  • 63
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    Electronic Resource
    The distribution of spinal projection neurons in the hypothalamus of the rat, studied with the HRP method (1980)
    Springer
    Experimental brain research 40 (1980), S. 79-87 
    Details
    ISSN: 1432-1106
    Keywords: Spinal tract neuron ; Hypothalamus ; HRP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution and number of hypothalamospinal tract (HST) neurons were studied following injections of horseradish peroxidase (HRP) at various levels of the rat spinal cord. The hypothalamus was divided into four areas and one nucleus, that is, the dorsal (DHA), posterior (PHA), medial (MHA) and lateral (LHA) hypothalamic areas and the paraventricular nucleus (PVN). The total numbers of HST neurons labeled with HRP varied according to the injection levels: 6,160 (C2 injections), 3,808 (T8), 1,961 (L1), 919 (L7) and 13 (S4). With C2 injections LHA contained 3,464 neurons, which accounted for 56% of the full number of HST neurons; similarly, PVN, 1,114 (18%); MHA, 865 (14%); DHA and PHA, 817 (12%). With L7 injections, LHA contained 444 labeled neurons, which accounted for 48% of the total; PVN, 327 (36%); MHA, 71 (8%); DHA with PHA, 77 (8%). As for the rostrocaudal distribution of labeled neurons, there was only a slight difference between the C2 and L6 injections in LHA, but no difference was noticed in PVN, DHA nor PHA. The present findings suggest that 70% of HST neurons may project to the cervical and thoracic cords. Although the number of labeled HST neurons decreased as the injection sites were placed caudally, no clearcut topographical arrangement was recognized in terms of the spinal projection levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236665
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  • 64
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    Positive two-stage carcinogenesis in female sprague-dawley rats using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and 12-o-tetradecanoylphorbol-13-acetate (TPA) as promotor (1980)
    Springer
    Virchows Archiv 385 (1980), S. 181-186 
    Details
    ISSN: 1432-2307
    Keywords: Tumor promotion ; Tumor initiation ; DMBA ; TPA ; Two-stage carcinogenesis experiment ; Carcinogenesis ; Cocarcinogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In contrast to a previous report by Shubik, the validity of the 2-stage skin carcinogenesis experiment was demonstrated in the rat. The modified experiment was carried out in female Sprague-Dawley rats using intragastrically administered DMBA as a carcinogen and the topically applied phorbol ester TPA as a promoter. Seven groups of animals were used. Two groups were treated with TPA only, two groups were initiated only with DMBA, two further groups were both initiated and promoted, and one group served as a control. Each of the initiated/promoted groups or only initiated or promoted groups contained one sub-group in which the animals had been bilaterally ovarectomized prior to the experiment. Hyperplasia of the dorsal epidermis occurred only in the promoted and in the initiated/promoted groups. Tumors of the back skin were observed exclusively after initiation/promotion. Ovarectomy — leading to a prolonged survival time of the animals — seems to be crucial for the manifestation of malignant skin tumors. Initiation/promotion also gives rise to tumors of the forestomach, the small intestine, the liver and the colon. Tumors in other organs (especially in the mammary gland and the Zymbal gland) were also be observed after initiation alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427403
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  • 65
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    Electronic Resource
    Differential effects of naloxone against the diazepam-induced release of behavior in rats in three aversive situations (1980)
    Springer
    Psychopharmacology 69 (1980), S. 101-105 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Naloxone ; Behavioral inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of naloxone on diazepam-induced release of behavior in aversive situations were investigated in rats. Naloxone (0.5 and 1 mg/kg-1) suppressed diazepam-induced eating in an unfamiliar situation and reduced (1 mg/kg-1) spontaneous food intake. Naloxone (1 mg/kg-1) canceled the increased lever pressing produced by diazepam in a conflict procedure in which one electric shock was delivered at each seventh press. Naloxone (1 mg/kg-1) failed to reverse the enhanced responding for food induced by diazepam in the presence of a signal previously paired with electric foot shocks. In this situation, naloxone alone reinforced the behavioral suppression. These results suggest that transmission mediated by opiate peptides may be involved in only some ‘disinhibitory’ effects of benzodiazepines. In addition, such a peptidergic transmission may play a role in the control of stress-induced behavioral suppression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426529
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  • 66
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    Effect of 5,7-dihydroxytryptamine on the development of tolerance to ethanol (1980)
    Springer
    Psychopharmacology 67 (1980), S. 143-146 
    Details
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; 5,7-Dihydroxytryptamine ; 5-HT ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 5,7-Dihydroxytryptamine (5,7-DHT) or the vehicle was administered once into both lateral ventricles of the rat. Desmethylimipramine (DMI) was administered IP prior to the intraventricular injection of 5,7-DHT to prevent the destruction of norepinephrine (NE) terminals. Following recovery from surgery, ethanol (5 g/kg, PO) or isocaloric sucrose was given daily for 25 days. Tests at 5-day intervals showed that chronic ethanol treatment produced tolerance to the motor impairment on the moving belt test and to hypothermic effects of ethanol. The 5,7-DHT treatment did not alter either the motor impairment or hypothermia produced by the initial dose of ethanol. However, 5,7-DHT treatment produced a 75% depletion of brain serotonin (5-HT) without altering NE concentration and retarded the development of tolerance to ethanol in both measurements. This study with a specific central depletor of 5-HT, without alteration in NE concentration, extends and supports our hypothesis that brain 5-HT modulates the development of tolerance to ethanol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431969
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  • 67
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    Electronic Resource
    Metrazol produces conditioned taste aversion in rats (1980)
    Springer
    Psychopharmacology 68 (1980), S. 257-259 
    Details
    ISSN: 1432-2072
    Keywords: Metrazol ; Conditioned taste aversion ; Rat ; Two bottle test preference ; Saccharin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Employing a two bottle drinking procedure where an animal's preference is measured between plain water and a novel fluid, it was found that the convulsant drug Metrazol produced a conditioned taste aversion to saccharin. This finding is contrary to that of previous reports and highlights the sensitivity of the two bottle method in detecting a taste aversion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428112
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  • 68
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    Electronic Resource
    The effects of diphenylhydantoin on rat behavior (1980)
    Springer
    Psychopharmacology 69 (1980), S. 183-185 
    Details
    ISSN: 1432-2072
    Keywords: DPH ; Genral activity ; Stereotypy ; Supersensitivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Animals were administered increasing doses of diphenylhydantoin (DPH) for 20 days. During withdrawal they were observed in an open field. The results suggest that chronic DPH administration leads to a central supersensitivity phenomenon. Possible interference of DPH with dopaminergic systems was discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427647
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  • 69
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    An observational method for quantifying the behavioural effects of dopamine agonists: Contrasting effects of d-Amphetamine and apomorphine (1980)
    Springer
    Psychopharmacology 69 (1980), S. 253-259 
    Details
    ISSN: 1432-2072
    Keywords: Rating scales ; Photocell activity cages ; Measurement ; Stereotypy ; d-Amphetamine ; Apomorphine ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel means of measuring and analysing behavioural effects of dopamine agonists is described and illustrated by a comparison of the effects of d-amphetamine and apomorphine in the rat. d-Amphetamine (0–15 mg/kg IP) produced significant dose- and time-dependent changes in responses such as locomotion, rearing and sniffing, but not in licking or gnawing. In contrast, apomorphine (0–5 mg/kg SC) produced significant increases in licking and gnawing, as well as in locomotion and sniffing, but no changes in rearing. The results are discussed in comparison with those obtained by other methods, such as photocell beam interruptions or stereotypy rating scales, and may be of importance in elucidating the functions of the forebrain dopamine projections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433091
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  • 70
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    Electronic Resource
    Following several days of continuous administration d-amphetamine acquires hallucinogenlike properties (1980)
    Springer
    Psychopharmacology 68 (1980), S. 197-200 
    Details
    ISSN: 1432-2072
    Keywords: Continuous amphetamine ; Hallucinogens ; Limb flicks ; Shakes ; Grooming ; Model psychosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats injected with LSD or mescaline show the behavioral syndrome which has been previously reported following injections of hallucinogens in higher mammals: limb flicks and whole body shakes. Although these behaviors are not elicited by acute injections of amphetamine, they are present in rats which have been pretreated for 108 h with a slow-release amphetamine pellet, given a 12h rest period, and then injected with d-amphetamine. Such pellet-pretreated animals also groom their body surface excessively. We propose that this novel syndrome which follows continuous amphetamine administration can serve as an animal model of the type of amphetamine psychosis that is produced by a similar drug regimen in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432141
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  • 71
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    Electronic Resource
    Mesenterico-caval shunt in rats (1980)
    Springer
    Research in experimental medicine 177 (1980), S. 79-84 
    Details
    ISSN: 1433-8580
    Keywords: Mesenterico-caval shunt ; Microsurgical procedure ; Patency rate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A microsurgical technique for mesenterico-caval shunting in the rat is described. The method results in a portal blood drainage from the upper abdominal contents whereas the blood of the mesenteric vein is shunted to the inferior caval vein. Controls were undertaken after 1 and 3 weeks, either visually or radiologically. Twenty-two of 26 surviving animals showed patency of the shunt. All animals had undisturbed blood supply to the portal stump.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01851635
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  • 72
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    Electronic Resource
    A technique for in vivo and in vitro studies on the preserved and transplanted rat kidney (1980)
    Springer
    Urological research 8 (1980), S. 107-112 
    Details
    ISSN: 1434-0879
    Keywords: Kidney transplantation ; Rat ; Renal ischaemia ; Renal preservation ; Microsurgical technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A modified technique for preservation and transplantation of rat kidneys, allowing precise control of the periods of warm and cold ischaemia, is presented. The donor kidney is placed in a continuously cooled micropuncture cup during the insertion. End-to-end anastomosis of arteries and veins is performed. The technique causes negligible circulatory changes on restoration of the blood flow. Eighty-nine consecutive transplantations are analysed. Complications from the vascular anastomoses occurred in 6% (5/89). In 53 survival experiments complications from the ureteric anastomoses occurred in 9% (5/53). The methodological scatter was small, with a distinct difference in the serum creatinine course and mortality of recipients obtaining kidneys subjected to cold is chaemia for different lengths of time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271437
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  • 73
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    Afferent neurons of the hypoglossal nerve of the rat as demonstrated by horseradish peroxidase tracing (1980)
    Springer
    Anatomy and embryology 158 (1980), S. 349-360 
    Details
    ISSN: 1432-0568
    Keywords: Afferent neurons ; Hypoglossal nerve ; Rat ; HRP-tracing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cell bodies of sensory neurons of the rat's hypoglossal nerve were demonstrated by the somatopetal horseradish peroxidase (HRP) transport technique. Labelled perikarya were found within the second and third cervical spinal ganglia and in the vagal sensory ganglia. After application of HRP to the cut peripheral trunk of the hypoglossal nerve about 200 labelled cell bodies were counted in each animal. The vast majority of the axons from cervical spinal ganglion cells reach the hypoglossal nerve via the descending ramus (N. descendens hypoglossi). However, there may exist an additional pathway, probably via the cervical sympathetic trunk. Application of HRP to the medial and lateral end branches led to a labelling of much fewer spinal ganglion cells while the number of labelled vagal sensory neurons remained unchanged. Thus, it is suggested that the majority of the cervical afferents of the hypoglossal nerve originates within the extrinsic tongue musculature and the geniohyoid muscle, whereas the vagal afferents may perhaps derive exclusively from the intrinsic muscles. Histograms of the mean diameters of labelled cell bodies show a predominance of very small perikarya. This contrasts with the diameter distribution of sensory perikarya labelled after HRP application to nerves supplying other skeletal muscles. It is therefore assumed that the afferent component of the hypoglossal nerve is composed mainly of small-calibre axons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301822
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  • 74
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    Macrophages in peripheral nerves (1980)
    Springer
    Acta neuropathologica 49 (1980), S. 43-49 
    Details
    ISSN: 1432-0533
    Keywords: Rat ; Peripheral nerve ; Macrophage ; Ultrastructure ; Histochemistry ; Acid phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cellular content of the endoneurium in peripheral nerves of normal adult rats was studied. Endoneurial cells with high light-microscopical activity of acid phosphatase were usually located close to blood vessels or near the perineurium. Cells with the ultrastructural appearance of macrophages showed the same distribution and accounted for 2–4% of the endoneurial cell nuclei profiles. These cells rapidly endocytosed carbon particles after endoneurial administration of colloidal carbon in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00692218
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  • 75
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    Ultrastructural study of Sertoli cells in rat seminiferous tubules during intrauterine life and the postnatal period (1980)
    Springer
    Anatomy and embryology 160 (1980), S. 11-27 
    Details
    ISSN: 1432-0568
    Keywords: Sertoli cells ; Rat ; Fetal and postnatal life ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sertoli cells have various functions: mechanical (creation of two compartments in the seminiferous tubules, migration of germinal cells), secretory (secretion of anti-Müllerian hormone, inhibin, androgen-binding-protein and estrogen) and phagocytic. We report an ultrastructural study of the rat Sertoli cell during maturation and consider possible correlations between the acquisition of certain morphological characteristics and certain functions. During fetal life, the Sertoli cell possesses differentiated zones of junction with the gonocytes and seems to have a role in the migration of the gonocytes towards the periphery of the seminiferous tubule. The Sertoli cell performs the phagocytosis of the gonocytes which degenerate during their migration, and seems to be the site of production of protein granules, whose presence can be related to the synthesis of anti-Müllerian hormone. After birth and before puberty, when the inclusions resembling secretory granules disappear, the Sertoli cell membranes in contact with spermatocytes II and spermatids differentiate, forming, through the differentiated junctional complexes, two compartments (adluminal and luminal) in the seminiferous tubules. Finally, they acquire the characteristics of active secretory cells, capable, in particular, of steroid synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315646
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  • 76
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    Innervation of the liver in guinea pig and rat (1980)
    Springer
    Anatomy and embryology 160 (1980), S. 239-252 
    Details
    ISSN: 1432-0568
    Keywords: Liver ; Innervation ; Adrenergic nerves ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The adrenergic innervation of rat and guinea pig liver is investigated using the glyoxylic-acid — paraformaldehyde method for fluorescent microscopical demonstration of adrenergic nerves and electron microscopy. The nerve distribution in the parenchyma of both animals is compared. The distribution of the liver nerves as detected with fluorescence microscopy is confirmed electron microscopically. The two species exhibit fundamental differences in their liver innervation: (1) In the guinea pig, a rich innervation is found in the trias as well as in the parenchyma. Many nerves traverse the entire liver lobules and may end near the central vein. The guinea pig hepatocyte innervation seems to be uniformly adrenergic. Electron microscopy shows that the varicosities of these nerves mostly form close contacts to the hepatocytes but also to other hepatic intralobular cells. (2) In the rat, the liver nerves are as a rule restricted to the triads, running mainly with smooth muscle containing blood vessels. It rarely happens that nerves penetrate into the lobule and come into contact with the peripherally located hepatocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305105
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  • 77
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    The ansa cervicalis and the infrahyoid muscles of the rat (1980)
    Springer
    Anatomy and embryology 159 (1980), S. 59-69 
    Details
    ISSN: 1432-0568
    Keywords: Infrahyoid muscles ; Motoneurons ; Spinal ganglion cells ; Axons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Perikarya of motoneurons and spinal ganglion cells attributed to infrahyoid muscle nerves of the rat were labelled by retrogradely transported horseradish peroxidase (HRP). For the differentiation of motor and sensory axons cross sections of the nerves were stained for acetylcholinesterase. Numbers and diameter distributions of perikarya and myelinated axons were determined. Motoneuronal perikarya innervating the infrahyoid muscles are located from the transition zone brain stem/spinal cord to the segment C 3. They are found mostly in the medial part of the Rexed laminae VII and VIII at the level of C 1 and C 2 and more ventrolaterally in C 3 and are therefore located to a large extent in areas until now not recognized to contain motoneurons. Our results provide evidence for a somatotopic organization of the motoneurons in the upper cervical spinal cord. The diameter distributions of motoneuronal perikarya and axons are in most cases bimodal, the two modes corresponding to α-and γ-motoneurons. In relation to the diameters of their perikarya α-axons are significantly thicker than γ-axons. In contrast to the motoneurons no clear correlation could be established between the sizes of perikarya of spinal ganglion cells and their peripheral processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00299255
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  • 78
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    Angioarchitectonics of rat cerebellar cortex during pre- and postnatal development (1980)
    Springer
    Acta neuropathologica 50 (1980), S. 131-138 
    Details
    ISSN: 1432-0533
    Keywords: Rat ; Cerebellum ; Vessels ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The adult arrangement and the development of stem vessels and capillaries was studied in the rat cerebellum. In principle, stem vessels branch and terminate at three levels: (1) the molecular layer, (2) the Purkinje cell-granular layer, and (3) the cerebellar white matter. All stem vessels are interconnected by the capillary network which is most dense in the Purkinje cell—granular layer. As in the neocortex, the stem vessels of the cerebellum are formed successively during development, so that the later they are formed the more superficial are their terminations. The formation of multiple stem vessels in the depths of fissures and sulci during both pre- and postnatal development may correlate to regional variations in, e.g., mitotic frequency or thickness of the external granular layer. The earliest “endo-parenchymal” branches are formed before the first neurons are present. Capillary growth by sprouting during the postnatal period parallels known regional differences in the timing of the neuronal maturation, e.g., increased synaptic density and oxidative metabolism. The findings in this investigation confirm and extend the results of an earlier morphometric study on capillary development in the cerebellar cortex. Although the angiogenetic factors remain unknown, the hypothesis of a link between the vascularization and the functional maturation of the brain is corroborated by the results. Knowledge of the normal vascular development seems necessary for an understanding of brain morphogenesis and for interpretation of primary pathogenetic mechanisms in various intoxications etc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00692863
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    Arrays of glycogen granules in the axoplasm of peripheral nerves at pre-ovoid stages of wallerian degeneration (1980)
    Springer
    Acta neuropathologica 50 (1980), S. 227-232 
    Details
    ISSN: 1432-0533
    Keywords: Wallerian degeneration ; Schmidt-Lantermann incisures ; Glycogen clusters ; Peripheral nerves ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phrenic and sciatic nerves of the rat were examined during the initial stages of Wallerian degeneration 4–48 h after axotomy about 5 mm below the level of transection. One of the first changes observed in transected axons was the appearance of glycogen granules and formation of clusters of particulate glycogen at the Schmidt-Lantermann incisures and at the nodes of Ranvier. Four hours after transection, glycogen granules were found at these sites mainly attached to the tubules of axoplasmic reticulum or dispersed in small clusters in the axoplasm. At later stages, glycogen particles increased in number and formed elongated clusters arrayed mostly longitudinally among axonal organelles filling stretches of axons about 2 μm long adjacent to the incisures and in nodal regions. The buld-up of glycogen clusters reached a peak at 22 h after axotomy, when longitudinal arrays of glycogen particles were found at about 70% of the incisures and nodes examined. The percentage of these sites containing glycogen clusters had already decreased 26 h after axotomy. When axonal degeneration advanced and axons contained only floculated material and swollen mitochondria, glycogen granules also disintegrated. It is of interest that glycogen particles accumulate in those regions of the internode where the axon will soon become disrupted during ovoid formation. The possible mechanisms leading to glycogen accumulation at these sites are discussed in relation to the active role of Schwann cells in Wallerian degeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688759
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  • 80
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    The early internal vascularization of the rat brain (1980)
    Springer
    Acta neuropathologica 50 (1980), S. 221-226 
    Details
    ISSN: 1432-0533
    Keywords: Rat ; Brain ; Vessels ; Prenatal ; Development ; Protein deprivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The internal vascularization of the brain was studied in foetuses of normal and protein-deprived rats from embryonic day (E) 12 to 15. The position of vascular branches showed distinct relations to the various zones of the neuroepithelium. The possibility that various parts of the vascular system may differ in function, maturation, and morphogenetic relations to the neuroepithelium must be considered. The distinct vascular layers were therefore given names relating them to the respective wall zone. The ingrowth of straight stem vessels from the epiparenchymal vascular plexus into the neuroepithelium and the formation of vascular branches close to the ventricular system were referred to as stage I of the internal vascularization. The resulting plexus was called the deep vascular plexus of the ventricular zone. Its formation followed the same temporospatial gradients as the formation of the marginal zone. Following the formation of the intermediate zone, more stem vessels entered the neuroepithelium and a superficial vascular plexus of the ventricular zone was formed (stage II). This plexus was positioned close to the border between the ventricular zone and the intermediate zone. Subsequently, vascular branches also formed plexuses of the intermediate and subventricular zones (stage III). No “intraepithelial” vessels were seen on E 12. The temporospatial gradients in the telencephalic vesicles were caudal to rostral and lateral to medial, starting in the parts corresponding to the ganglionic eminence in the floor of the lateral ventricle on E 13. Only the dorsomedial angles of the hemispheres showed no vessels on E 15. No obvious differences were seen between the normal and the protein-deprived foetuses regarding the timing and extent of vascularization or the size and appearance of wall zones in the immature central nervous (I-CNS).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688758
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  • 81
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    Hypothalamic lesions in rats with long-term streptozotocin-induced diabetes mellitus (1980)
    Springer
    Acta neuropathologica 52 (1980), S. 119-127 
    Details
    ISSN: 1432-0533
    Keywords: Hypothalmus ; Rat ; Streptozotocin ; Diabetes ; Morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixteen male Wistar rats, 1 year after injection of streptozotocin or vehicle, were fixed by whole-body perfusion, the brains were removed and processed for light and electron microscopy. Study of semithin sections from the hypothalamic area revealed changes in the arcuate nucleus and median eminence. The lesions, in comparison with controls, were subjected to a blind semiquantitative evaluation. The following changes were observed by light microscopy in diabetic rats: accumulation of glycogen (P〈0.01), degeneration of neurons (P〈0.05), hypotrophy of tanycytes (P〈0.01), and axonal changes. Electron microscopy of diabetic rats revealed that glycogen was increased in neuronal bodies and processes (axons, synapses), also in tanycytes, and glia cells. In neurons were seen: dilated and fragmented endoplasmic reticulum, degranulated ergastoplasm, loss of organelles, increased number of microtubuli, myelin figures, irregulatities in the form of nuclei, and appearance of chromatin. The tanycytes in diabetic animals were reduced in volume, had an increased nuclear cytoplasmic ratio, a reduced number of organelles, short basal processes, and almost complete loss of the apical processes. These changes demonstrate the existance, under experimental conditions, of an encephalopathy pathogenetically related to streptozotocin-induced diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688009
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  • 82
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    Effects of several lipidosis-inducing drugs upon the area postrema and adjacent medullary nuclei of adult rats (1980)
    Springer
    Acta neuropathologica 52 (1980), S. 179-187 
    Details
    ISSN: 1432-0533
    Keywords: Medulla oblongata ; Rat ; Chlorophentermine ; Chloroquine ; Lipidosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study is concerned with the question of whether or not amphiphilic drugs (chloroquine, quinacrine, perhexiline) that fail to induce general lipidosis in the central nervous system (CNS) of adult rats can produce lipidosis in a circumventricular organ (area postrema) not furnished with a blood-brain barrier. Chlorphentermine known to induce general lipidosis in CNS of adult rats served as reference compound. All drugs, when chronically applied in high oral doses, induced significant perikaryal lipidosis in the area postrema. In the adjacent nuclei (nucleus tractus solitarii, nucleus dorsalis nervi vagi, nucleus nervi hypoglossi, nucleus gracilis), only chlorphentermine caused generalized lipidosis, whereas the other drugs had either limited or no effects. The present findings strongly suggest that the exemption, of most regions of the CNS of adult rats, from lipidosis induced by chloroquine and others is due to hindered drug distribution across the blood-brain barrier, rather than being due to non-susceptibility of central neurons toward the lipidosis-inducing action of the drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00705806
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  • 83
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    Postnatale Entwicklung von Rattenthrombozyten: Die Volumenverteilung und elektrophoretische Beweglichkeit von Rattenthrombozyten während des ersten Lebensmonats (1980)
    Springer
    Annals of hematology 40 (1980), S. 421-428 
    Details
    ISSN: 1432-0584
    Keywords: Rat ; Thrombocytes ; Cell volume ; Electrophoretic mobility ; Haematopoiesis ; Ratten ; Thrombozyten ; Zellvolumen ; elektrophoretische ; Beweglichkeit ; Hämatopoese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Volumenverteilung von Rattenthrombozyten zeigt zwischen dem 5. und dem 8. Tag nach Geburt eine deutliche Zunahme im Modalvolumen. Bei rechnerischer Analyse der Kurven konnten keine deutlichen Anhaltspunkte für zwei diskrete Thrombozytenpopulationen gefunden werden. Da sich jedoch der Anstieg des Modalvolumens mit dem Beginn der Produktion einer neuen Erythrozytenpopulation deckt, und außerdem die Thrombozytenkonzentration im Blut in dieser Zeit deutlich ansteigt, können diese Veränderungen Ausdruck der Produktion einer zweiten Thrombozytenpopulation sein. Die mittlere elektrophoretische Beweglichkeit der Rattenthrombozyten fällt in den ersten drei Wochen nach Geburt nur geringfügig ab, während die der Erythrozyten im gleichen Zeitraum signifikant anstiegt.
    Notes: Summary The volume distribution curves of rat thrombocytes show a significant rise of the modal volume between days 5 and 8 after birth. No clear evidence for two distinct thrombocyte populations was obtained by computer analysis of the volume distribution curves. However, the increase of the modal volume of the platelets correlates with the production of a new erythrocyte population. In addition, the platelet concentration in the blood increases significantly during this time. These changes could indicate the production of a second thrombocyte population. The mean electrophoretic mobility of rat thrombocytes decreases only slightly during the first 3 weeks after birth, while it increases for erythrocytes significantly during the same period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01029684
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  • 84
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    Fine structure of fetal rat calvarium; provisional identification of preosteoclasts (1980)
    Springer
    Calcified tissue international 31 (1980), S. 21-28 
    Details
    ISSN: 1432-0827
    Keywords: Rat ; Calvarium ; Electron microscopy ; Preosteoclasts ; Osteoclasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02407163
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  • 85
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    An automatic microspectrophotometric scanning method for the measurement of bone formation rates in vivo (1980)
    Springer
    Calcified tissue international 32 (1980), S. 63-68 
    Details
    ISSN: 1432-0827
    Keywords: Rat ; Bone formation ; Fluorochrome ; Microphotometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A method for quantitative studies of the formation rate of bone has been developed. After vital staining with calcein, the fluorescence of a bone section was measured with a microphotometer controlled by a mini computer. After staining the bone structure with alizarin red S in a second step, the section was measured in transmitted light. The two data sets were combined and the shortest distances between the bone surface and the fluorescence lines were computed. With this information the distance distribution and the bone area between the label and the surface could be calculated in two different ways: with the single labeling and the continuous labeling techniques. The advantages and disadvantages of the two methods are discussed and compared with those of other techniques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02408522
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  • 86
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    A quantitative histologic analysis of the growing long bone metaphysis (1980)
    Springer
    Calcified tissue international 32 (1980), S. 113-122 
    Details
    ISSN: 1432-0827
    Keywords: Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02408530
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  • 87
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    Role of growth hormone in experimental phosphorus deprivation in the rat (1980)
    Springer
    Calcified tissue international 32 (1980), S. 105-112 
    Details
    ISSN: 1432-0827
    Keywords: Rat ; Hypophysectomy ; Dietary phosphorus deprivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02408529
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  • 88
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    Enhanced suppression of a conditioned avoidance response by haloperidol but not phenoxybenzamine in rats with bilateral parafascicular lesions (1980)
    Springer
    Experimental brain research 40 (1980), S. 164-169 
    Details
    ISSN: 1432-1106
    Keywords: Rat ; Avoidance conditioning ; Parafascicular nucleus ; Dopamine ; Noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male rats were subject to bilateral lesions in the parafascicular nucleus (PF) of the thalamus. The lesions had little or no effect on the performance of a pre-operatively acquired conditioned avoidance response. However, the PF lesioned animals displayed an enhanced response to the dopamine receptor blocking agents haloperidol or pimozide but not to the noradrenaline receptor blocking agent phenoxybenzamine. The results indicate that intralaminar thalamic nuclei and dopaminergic extrapyramidal motor pathways are functionally connected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00237534
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  • 89
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    Electronic Resource
    Axonal projections and conduction properties of olfactory peduncle neurons in the rat (1980)
    Springer
    Experimental brain research 39 (1980), S. 241-248 
    Details
    ISSN: 1432-1106
    Keywords: Olfactory peduncle neurons ; Axonal branching ; Supernormal period ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electrophysiological methods were employed to study the axonal properties of the neurons of anterior olfactory nucleus (AON), transition zone (TZ), and rostral prepyriform cortex (RPPC) and their projections towards the ipsilateral and contralateral olfactory bulb (IOB, COB) in the rat. Of 91 antidromically driven cells, 39 (43%) and 32 (35%) responded to IOB and COB stimulation, respectively; 20 (22%) were discharged from both bulbs. Collision tests performed on the latter group indicated that these neurons have a short main axon which divides near the soma, projecting one branch to the COB and a thinner one toward the IOB. Mean conduction velocities of axons projecting to the IOB and the COB were 0.4 m/s and 0.7 m/s, respectively, the faster conducting axons having shorter refractory periods. Of the 38 neurons tested, 92% showed decreases in threshold and latency (up to 20% of control antidromic latency) after a test volley that was preceded by a conditioning pulse at intervals of 20–215 ms. Latency decreases were greater for slowly conducting axons than for the faster ones. These after-effects of impulse activity in OB afferent axons were attributed to the presence of a supernormal period of increased conduction velocity and excitability similar to that found in the olfactory nerve (Bliss and Rosenberg, 1974).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00237113
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  • 90
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    Electronic Resource
    Swimming in the rat: Analysis of locomotor performance in comparison to stepping (1980)
    Springer
    Experimental brain research 40 (1980), S. 374-382 
    Details
    ISSN: 1432-1106
    Keywords: Cinematography ; Electromyography ; Locomotion ; Rat ; Swimming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Swimming in a mammalian quadruped, the rat, is analyzed in kinematic (joint angles) and electromyographic (EMG) terms. Data were collected on the movements of the hip, knee, ankle, and toe joints and three principle extensors and three flexors of the right hindlimb and compared with similar data collected on the same rats during treadmill stepping. The flexion, or protraction phase of swimming and stepping had many elements in common, including a similarity of EMG activity patterns and corresponding limb movements. However, in the extension, or retraction phase, there were notable differences. Although joint-extensor muscles were all coactive in both conditions, the brevity of the swimming extensor phase precluded the characteristic variation in EMG activity levels seen in the extensors in stepping. The flexors, in particular semitendinosus (ST), exhibited bursts of activity at the end of the extensor phase of swimming which were not present during the comparable period of stepping. The extra burst in ST produced a very rapid knee flexion at this time. Whereas the range of hip joint movement was similar in the two conditions, the ranges of the knee and ankle joints were expanded during swimming. Overall, the evidence suggests that swimming is a very rapid form of a basic locomotor pattern in which the extensors are driven to their maximum contraction rate. The extra extension of the limb derives from the absence of ground reaction forces, allowing the knee and ankle joints to fully extend. The added bursts in the flexors remain to be explained. A discussion of these results in terms of current theories of single limb locomotor pattern generation is presented.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236146
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  • 91
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    Electronic Resource
    Changes in the glomerular filtration rate after unilateral nephrectomy in rats (1980)
    Springer
    Pflügers Archiv 385 (1980), S. 161-165 
    Details
    ISSN: 1432-2013
    Keywords: Glomerular filtration rate ; Unilateral nephrectomy ; Compensatory hypertrophy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in the glomerular filtration rate (GFR) were studied in rats, 4 h to 4 weeks after unilateral nephrectomy (NX). The GFR was determined with a technique using51Cr-EDTA and a single timed blood sample. The GFR determined in this way corresponded with the GFR calculated by two compartment analysis and with the plasma levels of creatinine and urea. Increases in the GFR, compared with half the GFR of sham operated rats, were observed as early as 4 h after NX. This increase was entirely due to an increase in the GFR per gram of kidney, since no increase in kidney weight was observed at that time. After the initial increase, the GFR remained at that level during the first 48 h after NX. At 48 h a significant increase in kidney weight per 100 g body weight had taken place. The longterm changes in the GFR amounted to an increase of about 80% of that of sham operated rats after 3–4 weeks. After 4 weeks, the increase in the GFR of the remaining kidney was due to an increase in kidney weight of 35% as well as an increase in the GFR per gram of kidney of 20%. These data indicate that the increase in the GFR of the remaining kidney after unilateral NX occurs rapidly and is independent of an increase in kidney weight. Compensatory hypertrophy develops at a later stage and helps to maintain the increased function of the single remaining kidney.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00588697
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  • 92
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    Increase in plasma renin activity, water intake and blood pressure following application and reapplication of a renal artery clip (1980)
    Springer
    Pflügers Archiv 385 (1980), S. 211-215 
    Details
    ISSN: 1432-2013
    Keywords: Rat ; Renal hypertension ; Plasma renin activity ; Water intake ; Declipping ; Reclipping ; Converting enzyme inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Application of a renal artery clip in rats with an undisturbed contralateral kidney caused a sustained increase in blood pressure and a transient rise of plasma renin activity and water intake. The response of blood pressure, plasma renin activity and water intake was augmented after reapplication of the clip to normotensive declipped rats (renal hypertensive rats, from which the clip had been removed 24 h before the reapplication). The time-course of the changes of blood pressure, plasma renin activity and water intake were similar after the initial application as after reapplication of the clip. Administration of an inhibitor (SQ 14.225) of the converting enzyme abolished the increase in blood pressure and water intake after reapplication of the clip. These data indicate a critical role of renin in the rise of blood pressure and water intake after initial application of a renal artery clip as well as after reapplication of the clip to declipped rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00647459
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  • 93
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    Electronic Resource
    Glomerular tubular balance of renald-glucose transport during hyperglycemia (1980)
    Springer
    Pflügers Archiv 384 (1980), S. 39-47 
    Details
    ISSN: 1432-2013
    Keywords: d-Glucose ; Tubular Transport ; Glomerulotubular balance ; Micropuncture ; Clearance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract d-Glucose transport in the kidney of glucose loaded rats was investigated using clearance and micropuncture techniques. The range of plasma glucose concentration in clearance experiments was 20–140 mmol·l−1 and in micropuncture experiments 17–94 mmol·l−1. 1. During hyperglycemia, the glucose concentration in endproximal tubular fluid was elevated above that in arterial plasma. At plasma concentrations above 60 mmol l−1 intratubular glucose concentration was found to be about 1.2 times higher than in plasma. 2. At endproximal puncture sites TF/Posmol was unity throughout the investigated range of hyperglycemia. 3. Proximal tubular glucose reabsorption during hyperglycemia is close to saturation which is compatible to aK m=10.8 mmol l−1 as determined previously. 4. Passive glucose permeability does not change during hyperglycemia. The permeability constant of 2.03·10−5 cm·s−1 does not differ significantly from that during normoglycemia, 1.9·10−5 cm·s−1. 5. Single nephron glomerular filtration rate (SNGFR) and fluid reabsorption in the proximal convolution (C) were significantly correlated during hyperglycemia (r=0.78,P〈0.001). Fractional volume reabsorption during hyperglycemia was decreased to 0.36 as compared to control, but during hyperglycemia it was not affected by the magnitude of the glucose plasma concentration. 6. During hyperglycemia, proximal tubular glucose reabsorption (TG) was correlated to SNGFR (r=0.64,P〈0.001). This relation became insignificant when the influence of volume reabsorption (C) is controlled for (r=0.17,P〉0.5). However, the significance of the correlation between TG and C persists when the influence of SNGFR is held constant. 7. Calculations indicate that when glucose reabsorption was doubled, et sodium transport was increased about fourfold. 8. In hyperglycemia, renal transport rate (TG), when factored by renal glomerular filtration rate (GFR) seems to be linearly related to glucose plasma concentration. Up to endproximal puncture site 25.5% and by the entire kidney 68.2% of the tubular glucose load were reabsorbed. The difference may be attributed either to glucose transport systems which are localized distal to the proximal convoluted tubules and/or to an inhomogenity of the glucose transport in the different types of nephrons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00589512
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  • 94
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    Acid base status in unanesthetized, unrestrained guinea pigs (1980)
    Springer
    Pflügers Archiv 384 (1980), S. 93-97 
    Details
    ISSN: 1432-2013
    Keywords: Guinea pig ; Rat ; Anesthesia ; Chronic cannulation ; Blood acid-base status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acid-base status of arterial blood was measured in chronically cannulated, unanesthetized, unrestrained guinea pigs. Normal values were: pH=7.444±0.032,PaCO2=35.7±4.4; HCO 3 − =24.4±2.8; BE=+0.4±2.1 (n=69) andPaO2=91.9±7.3 (n=25) (Values are mean±S.D.). Induction of light anesthesia with thiopentone caused a respiratory depression (decrease inPaO2) accompanied by respiratory acidosis (increase inPaCO2 and decrease in pH) and a development of slight metabolic acidosis (decrease in base excess and standard bicarbonate). Acid base parameters of guinea pigs are compared to those obtained from rats under identical experimental conditions.
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    URL: http://dx.doi.org/10.1007/BF00589520
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  • 95
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    Oxygen supply of the brain cortex (rat) during severe hypoglycemia (1980)
    Springer
    Pflügers Archiv 387 (1980), S. 121-126 
    Details
    ISSN: 1432-2013
    Keywords: Local tissuepO2 ; Hypoglycemia ; Brain cortex ; ECoG ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oxygen supply of the brain cortex together with changes in the electrocorticogram (ECoG) were investigated during and after insulin induced hypoglycemia in 13 anaesthetized rats. Local oxygen partial pressures (pO2) on the parietal cortex were continuously measured with a multiwire surface electrode of the Clark type. During early hypoglycemia with a mean arterial glucose concentration [G]a of 2.81 (SD ±0.40) mmol/l, the local tissuepO2 did not change significantly as compared to thepO2 values recorded during the control period with a normal [G]a of 4.51 (SD±0.70) mmol/l. During severe hypoglycemia at a [G]a of 1.39 (SD±0.2) mmol/l,pO2 began to increase continuously on all 104 measuring sites, independently of changes in arterial blood pressure and ECoG. During a period of 7–18 min of isoelectricity, tissuepO2 remained elevated so long as blood pressure did not decrease. After injection of a 25% glucose solution,pO2 gradually decreased to control values within 30–60 min in most experiments. We conclude from these results that oxygen supply is generally improved during severe hypoglycemia. We assume that the increase in tissuepO2 is mainly caused by an increase in microflow. Thus, the neuronal damage occurring after severe hypoglycemia, as reported in literature, cannot primarily be caused by an oxygen deficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584262
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  • 96
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    Effect of feeding a high protein diet on solute-coupled water absorption from rat colon (1980)
    Springer
    Pflügers Archiv 388 (1980), S. 165-168 
    Details
    ISSN: 1432-2013
    Keywords: Colon ; Water absorption ; Electrolyte absorption ; High protein diet ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using an in vivo sac technique, net transport of water, Na, Cl and K was studied in the colon ascendens of rats fed either a high carbohydrate (HC) or high protein (HP) diet, since water intake is elevated in HP-rats. The ligated colon sacs were filled with isotonic Krebs-Henseleit solution. Net Na and Cl absorption rates related to 1 g intestinal dry weight were 46% and 30% higher in HP-rats compared with HC-rats. Net water absorption in HP-rats exceeded that in HC-rats by 115%. Therefore the ratio between net water absorption and net absorption of solutes was higher in HP-rats than in HC-rats, and thus the hypertonicity of the absorbate was lower in the HP-rats. There was a net secretion of K in both groups of rats to about the same extent. Experiments with22Na indicate that the increased net Na absorption in HP-rats was due to an increased unidirectional Na transport from the lumen to the blood side of the colon. The group difference in the ratio between net absorption of water and solutes might be a manifestation of regulatory mechanism controlling intestinal water absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584123
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  • 97
    Electronic Resource
    Electronic Resource
    Studies on liver toxicants (1980)
    Springer
    Archives of toxicology 43 (1980), S. 257-262 
    Details
    ISSN: 1432-0738
    Keywords: Bromobenzene ; Cytochrome P-450 ; Cytochrome reductase ; Glucuronyltransferase ; Lipoperoxidation ; Liver ; Mixed-function oxidase ; Peroxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In acute oral studies, the effect of bromobenzene on hepatic microsomal enzymes was investigated. Neither glucuronyltransferases nor cytochrome c reductase showed significant changes. Most of the mixed-function oxidases studied were inhibited with the exception of ketamine-N-demethylase. The data indicate that bromobenzene or its epoxide acts on cytochrome P-450 but not on all cytochrome P-450 species, and does not affect the reductase and the glucuronyltransferases. Microsomal lipoperoxidation and microsomal H2O2 formation were increased.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00366181
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  • 98
    Electronic Resource
    Electronic Resource
    Effect of pesticides on scheduled and unscheduled DNA synthesis of rat thymocytes and human lymphocytes (1980)
    Springer
    Archives of toxicology 45 (1980), S. 101-108 
    Details
    ISSN: 1432-0738
    Keywords: Pesticides ; DNA repair ; Human lymphocytes ; Man ; Rat thymocytes ; Rat ; DNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The action of seventeen pesticides (insecticides, fungicides and herbicides) has been studied with short-term in vitro system using rat thymocytes and/or human lymphocytes. The parameters studied were: a) the action of chemicals tested in scalar doses on DNA synthesis of rat thymocytes; b) damage exerted by pesticides on human lymphocyte DNA measured as unscheduled DNA synthesis; c) the interference of chemicals tested with human lymphocyte repair capability after damage exerted on cells by ultraviolet rays. The results obtained suggest that some of tested pesticides don't induce damages to human lymphocyte DNA, some others elicit low DNA repair if compared to the repair following a standard ultraviolet irradiation and some of them (6/17) exert a marked inhibition of cell repair processes after ultraviolet irradiation. Data are discussed on the basis of a possible role played by these substances as carcinogenic agents in the environment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01270907
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  • 99
    Electronic Resource
    Electronic Resource
    Toxic effect of various selenium compounds on the rat in the early postnatal period (1980)
    Springer
    Archives of toxicology 45 (1980), S. 207-211 
    Details
    ISSN: 1432-0738
    Keywords: Selenate ; d,l-selenomethionine ; d,l-selenocystine ; Dimethyl selenide ; Trimethylselenonium ion ; Toxicology ; Cataract ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxic effect of selenium compounds (sodium selenate,d,l-selenomethionine,d,l-selenocystine, dimethyl selenide, and trimethylselenonium ion) was tested in 10-day old male rats. Increasing doses of the compounds were administered an s.c. injection and control animals were not injected. All compounds tested were lethal. Eye lens cataract was induced by the administration of selenate,d,l-selenomethionine, andd,l-selenocystine, while dimethyl selenide and trimethylselenonium ion failed to cause cataract. The cataractogenic effect of the above compounds may be attributed to their interference with glutathione metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02419000
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  • 100
    Electronic Resource
    Electronic Resource
    Effects of excess 1,25-dihydroxycholecalciferol in young rats (1980)
    Springer
    Archives of toxicology 43 (1980), S. 155-161 
    Details
    ISSN: 1432-0738
    Keywords: 1α,25-dihydroxycholecalciferol ; Calcification ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The oral administration for 5 days of excess 1α,25-dihydroxychole-calciferol [1,25(OH)2D3] at doses of 1, 5, and 25 μg/kg to rats, beginning at the age of 2 or 10 days, produced dose-dependent reductions in weight development and additional calcification near the skeleton. Alizarin red S stained skeleton revealed calcific deposits near the bones of the head, near the neural arches, between the ribs, along the bones both of the fore limbs and, to a lesser extent, of the hind limbs. Historically, the deposits appeared to be localized primarily in the subepithelial connective tissues. Starting treatment with 1,25(OH)2D3 (25 μg/kg for 5 days) at the age of 20 days produced additional calcification in 1 of 8 rats at only 1 location (lower jaw). Additional calcification as described above could no longer be induced by 1,25(OH)2D3 in 30-day-old rats using doses up to 25 μg/kg and 10 daily treatments. We conclude that the sensitivity of young rats to 1,25(OH)2D3-induced additional calcification, which differs in localization from that observed in adult rats, decreases with the maturation of the animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00297581
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