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  • Articles: DFG German National Licenses  (3,949)
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  • 101
    ISSN: 1432-2072
    Keywords: Schedule-induced polydipsia ; SIP ; Clozapine ; Raclopride ; SCH 23390 ; Dopamine D1 antagonist ; Dopamine D2 antagonist ; Major tranquilizers ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of clozapine (CLOZ) upon acquired schedule-induced polydipsia in rats were compared to the effects of the dopamine (DA) D1 antagonist SCH 23390 (SCH) and the DA D2 antagonist raclopride (RAC). All three compounds suppressed water consumption, but only SCH and RAC decreased drinking efficiency. SCH was the only compound with an effect on panel pressing (PP), causing suppression even at a dose without effect upon water intake. SCH also affected the temporal pattern of licking (TPL) at all doses, while clozapine, 10 mg/kg, only affected the pattern acutely, and raclopride was without effect. In conclusion, PP and the TPL are more sensitive to D1 than D2 blockade. While PP and the TPL are more sensitive than water intake to D1 blockade, the opposite is true for D2 blockade. It is possible to differentiate between DA D1/D2 antagonists and CLOZ in this model, focusing upon reduction in water consumption, with and without reduction in drinking efficiency. Furthermore, it is possible to differentiate between D1 and D2 blockade by analyzing water consumption, PP and the TPL.
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  • 102
    ISSN: 1432-2072
    Keywords: Haloperidol ; Cocaine ; Apomorphine ; Stereotypy ; Locomotor activity ; Sensitization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment investigated the possibility that rats maintained on chronic haloperidol treatment would show increased behavioral responsiveness to cocaine, similar to that observed in human stimulant abusers who are chronically treated with neuroleptics. Thus, the effects on locomotion and stereotyped behavior of intermittent injections of cocaine were investigated in female rats receiving chronic haloperidol treatment. Daily injections of haloperidol (0.2 mg/kg, IP) or vehicle were administered for 6, 12 or 18 days prior to the start of testing with cocaine and were then continued throughout cocaine testing. All rats received four doses of cocaine (0.0, 3.0, 7.5, or 15.0 mg/kg, IP) in random order with an intervening vehicle day between successive drug days. The four dose sequence of cocaine was repeated a total of four times. Initial cocaine administration produced dose dependent increases in locomotion and stereotyped behavior. When the sequence of cocaine doses was repeated, differences among treatment groups emerged. Groups treated with haloperidol exhibited heightened locomotion in response to cocaine and with repeated injections, showed a higher rate of behavioral sensitization than control animals. These differences in the behavioral response to cocaine were maintained for at least 2 months following termination of daily haloperidol treatment. In order to examine the mechanisms underlying this heightened responsiveness to cocaine, apomorphine-induced locomotion (dose range, 0–250 µg/kg, SC) was determined. Regardless of dose, rats treated with haloperidol showed different temporal patterns of locomotion in response to apomorphine suggesting that the increased response to cocaine was related to changes in dopaminergic receptor sensitivity.
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  • 103
    ISSN: 1432-2072
    Keywords: Ultrasonic vocalizations ; Defense ; Pain ; Fear ; Aversion ; Social interactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was carried out to determine whether 22–28 kHz vocalizations emitted during intermale interactions in adult rats were related with a state of fear, aversion or resulted from painful stimulation. Vocalizations in the 22–28 kHz range were measured in male rats during non-aggressive and aggressive social interactions; when given foot shock with a partner; during non-aggressive social interactions after an injection of (i) acetic acid (1%, IP); (ii) pentylenetetrazol (20–30 mg/kg, IP) and (iii) lithium chloride (63.8 mg/kg, IP). Ultrasonic vocalizations were consistantly detected in all rats while the animals displayed defensive or submissive postures when tested as intruders confronted with offensive residents or when administered foot shocks. Only occasional vocalizations were emitted, even in the presence of a partner, when the animals had received other painful or aversive treatments. These data support the hypothesis that 22–28 kHz vocalizations during intermale interactions are associated with defensive postures and are not the consequence of a state of fear or aversion.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 111 (1993), S. 207-214 
    ISSN: 1432-2072
    Keywords: Feeding ; Striatum ; Nucleus accumbens ; Morphine ; Opiates ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both systemic and intracranial administration of morphine can result in spontaneous feeding in nondeprived rats. The present investigation was conducted to examine the involvement of the striatum in this phenomenon. Morphine sulfate (0, 0.5, 1.0, 5.0, 10.0, and 20.0 µg/0.5 µl) was microinjected into five discrete striatal subregions in non-deprived rats: the nucleus accumbens, the ventromedial striatum, the ventrolateral striatum, the anterior dorsal striatum, and the posterior dorsal striatum. Feeding, drinking, locomotion, rearing, and food intake were measured over 4 h after infusion. Results indicate that the striatum is a heterogeneous structure with regard to the regulation of opiate-induced feeding behavior and locomotor activity. Morphine infusion into anteroventromedial regions including the nucleus accumbens resulted in a marked hyperphagia that was generally delayed in onset; much smaller increases or no change in feeding occurred after administration into more dorsal, lateral and posterior areas. It is hypothesized that there may exist within the striatum an anatomical gradient that is most sensitive to opiate-induced feeding within the anteroventromedial sector. Since this area has extensive connections with other brain sites sensitive to opiate-induced feeding, it may be a critical part of an opiatergic feeding system within the brain. In addition, a possible role for the anteroventromedial striatum in compulsive feeding and bulimia is discussed.
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  • 105
    ISSN: 1432-2072
    Keywords: Radial maze ; Spatial memory ; Scopolamine ; Cholinomimetics ; ACE inhibitors ; Angiotensin II antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cholinomimetic and non-cholinomimetic agents on spatial memory using a novel task in the 12-arm radial maze were investigated. The task was designed to reduce the tendency to use non-spatial strategies. Animals were repeatedly trained to retrieve food rewards from three arms, until a criterion level of performance was reached. Scopolamine (0.03 and 0.1 mg/kg SC), but not N-methylscopolamine (0.1 mg/kg SC) disrupted performance of this task. Physostigmine (0.3 mg/kg SC) and pilocarpine (30 mg/kg SC) completely reversed the deficit of performance produced by scopolamine. Furthermore, the ACE inhibitor Hoe 288 (10 nmol ICV) and the angiotensin AT1 receptor antagonist losartan (10 mg/kg SC) also significantly attenuated the scopolamine-induced deficit. These results show that this novel task in the radial maze is sensitive to the disruptive effects of scopolamine and can identify cognitive enhancing effects of both cholinomimetic and non-cholinomimetic drugs. Thus, this maze task provides a useful model for the evaluation of novel cognitive enhancing agents.
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  • 106
    ISSN: 1432-2072
    Keywords: Spatial learning ; Rat ; Muscarinic ; Nicotinic ; Receptors ; Chronic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nicotine, scopolamine, oxotremorine, diisopropyl-fluorophosphate (DFP) and tetrahydroaminoacridine (THA) were administered chronically to different groups of rats in doses reported to alter central muscarinic and/or nicotinic receptro numbers. Beginning 24 h after final drug injection, the groups were compared to a vehicle control group on acquisition of a hidden platform position in the Morris water maze over 20 trials with a 30-min inter-trial interval. Chronic treatment with either nicotine or scopolamine significantly improved the rate of learning, but oxotremorine and DFP retarded learning and THA had no effect on learning. The chronic drug effects on behaviour were consistent with known effects of the injected drugs on muscarinic and nicotinic binding in the forebrain and on the sensitivity of frontal cortex neurones to iontophoretically applied cholinoceptor agonists. However, alternative explanations for the observed changes cannot be ruled out, since the drugs used are known to have a wide range of effects on other neurotransmitters.
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  • 107
    Electronic Resource
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    Psychopharmacology 113 (1993), S. 177-186 
    ISSN: 1432-2072
    Keywords: Rat ; Behavior ; Microstructure ; Scaling measures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies demonstrated that drug effects on the movement sequences of rats in unconditioned motor activity paradigms can be quantified by scaling measures that describe the average relationship between a variable of interest and an experimental parameter. However, rats engage in a wide variety of geometrically distinct movements that can be influenced differentially by drugs. In this investigation, the extended scaling approach is presented to capture quantitatively the relative contributions of geometrically distinct movement sequences to the overall path structure. The calculation of the spectrum of local spatial scaling exponents,f(d), is based on ensemble methods used in statistical physics. Results of thef(d) analysis confirm that the amount of motor activity is not correlated with the geometrical structure of movement sequences. Changes in the average spatial scaling exponent,d, correspond to shifting the entiref(d) function, and indicate overall changes in path structure. With the extended scaling approach, straight movement sequences are assessed independently from highly circumscribed movements. Thus, thef(d) function identifies drug effects on particular ranges of movement sequences as defined by the geometrical structure of movements. More generally, thef(d) function quantifies the relationship between microscopically recorded variables, in this paradigm consecutive (x, y) locations, and the macroscopic behavioral patterns that constitute the animal's response topography.
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  • 108
    ISSN: 1432-2072
    Keywords: Diisopropylfluorophosphate ; Atropine ; Somatostatin receptors ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acute and chronic administration of diisopropylfluorophosphate (DFP), an inhibitor of acetylcholinesterase (AChE), and of atropine, a blocker of muscarinic cholinergic receptors, did not affect somatostatin-like immunoreactivity (SLI) content in the frontoparietal cortex and hippocampus of rats. Acute and chronic DFP administration increased the number of specific125I-Tyr11-somatostatin (125I-Tyr11-SS) receptors in synaptosomes from the frontoparietal cortex but not in those from the hippocampus and did not change the affinity constant. This increase in125I-Tyr11-SS binding was not due to a direct effect of DFP on somatostatin (SS) receptors since no rise of binding was produced by high concentrations of DFP (10−5 M) when added in vitro. The increase could be blocked by pretreatment with atropine. The acute administration of atropine alone had no observable effect on the number of SS receptors. However, repeated atropine administration produced a significant decrease in the125I-Tyr11-SS binding in synaptosomes from the frontoparietal cortex but not in those from the hippocampus although the affinity constant was unchanged. The results suggest that interactions between somatostatinergic and cholinergic receptors may be important in the rat frontoparietal cortex.
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  • 109
    ISSN: 1432-2072
    Keywords: Cocaine ; Amphetamine ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats with different behavioral histories, defined by rearing and housing in either an enriched condition (EC) or an isolation condition (IC), were trained in a two-lever operant procedure to discriminate 5.0 mg/kg cocaine from saline. In cocaine dose-generalization tests, the IC rats exhibited an ED50 (1.01 mg/kg) significantly lower than the EC rats (ED50:1.55 mg/kg). The cocaine-appropriate responding was emitted when the rats were treated withd-amphetamine, and for thed-amphetamine test doses the ED50 (0.19 mg/kg) was again significantly lower for the IC rats compared to the ECs (ED50:0.33 mg/kg). These data suggest that IC rats are more sensitive to the stimulus properties of indirect dopaminergic agonists than EC rats and highlight the importance of environmental variables in governing an organism's response to the stimulus properties of abused drugs.
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  • 110
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    Pflügers Archiv 422 (1993), S. 523-529 
    ISSN: 1432-2013
    Keywords: Confocal microscopy ; Fluorescence microscopy ; Proximal tubule ; 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluorescein ; Intracellular pH ; Viability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Confocal laserscan microscopy with a dual-excitation device was used to record intracellular pH (pHi) regulation in rat proximal convoluted tubules microperfused in vivo. Cells were loaded with the pH-sensitive, fluorescent dye 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Single cells could be distinguished within the tubules and separate measurements were possible. Application of an NH4Cl pulse by peritubular perfusion caused an immediate increase in intracellular pH. Intraluminal injection of NH4Cl led to a slower increase in intracellular pH. In both cases, cessation of perfusion led to an immediate acidification. Peritubular perfusion with 300 μM 4,4′-diisothiocanatodihydrostilbene-2, 2′-disulphonic acid (H2DIDS) caused an intracellular alkalinisation. Microperfusion, pH-sensitive dyes and confocal laserscan microscopy provide a new non-invasive method to measure intracellular pH effectively in individual cells of near-surface structures of the intact kidney.
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  • 111
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    Springer
    Archives of toxicology 67 (1993), S. 510-513 
    ISSN: 1432-0738
    Keywords: Pyrethroids ; Acute toxicity ; Drug metabolism inhibitors ; Neonatal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X2=5.97;p〈0.05) and PERM (X2=4.37;p〈0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.
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  • 112
    ISSN: 1432-0738
    Keywords: Rat ; Hamster ; Microsomes ; Scoparone ; Cytochrome P450 ; Species differences ; Induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hamster is known to display very high rates of monooxygenase-mediated biotransformation. In comparison with other species little knowledge has been gathered with respect to the nature of its cytochrome P450 enzymes and their respective inducibility. We studied the consequences of induction of P450 enzymes in rats and Syrian golden hamsters using the regioselective oxidative O-demethylation of the coumarin derivative scoparone. This metabolic conversion indicates differential effects of P450 inducers in the rat, in which various types of inducers cause different shifts in the isoscopoletin/scopoletin metabolite ratio (I/S-ratio). Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats. In rat liver microsomes total demethylation rates of scoparone increased upon in vivo treatment with phenobarbital or ß-naphthoflavone. Phenobarbital reduced the I/S-ratio whereas ß-naphthoflavone caused an increase in this ratio. In hamster liver microsomes both phenobarbital and β-naphthoflavone treatments resulted in a decrease in the I/S ratio. In this species the total scoparone demethylation rate was not much affected by phenobarbital, but β-naphthoflavone caused a huge increase in over-all scoparone biotransformation. In both species, dexamethasone, isoniazid and clofibrate were much less effective. In contrast to the rat, in the hamster the scoparone biotransformation profile cannot be used to differentiate between phenobarbital- or β-naphthoflavone-treated animals.
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  • 113
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    Archives of toxicology 67 (1993), S. 120-125 
    ISSN: 1432-0738
    Keywords: Amoscanate ; Retinal degeneration ; Rat ; Electroretinography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amoscanate, a substance which damages photoreceptors, was administered orally to Wistar rats in doses of 10, 40, and 125 mg/kg body weight once daily for 3 or 10 days. At both times electroretinographic, ophthalmological, and histopathological examinations of the retina were carried out to compare the sensitivity of conventional methods and to test electroretinography (ERG) for suitability for use in toxicity studies. Time-dependent and dose-dependent effects were found by electroretinography and light microscopy. However, signs of retinal changes appeared earlier and more distinctly in the electroretinogram. Ophthalmological fundus examination in albino rats yielded no characteristic correlate. In conclusion, electroretinography constitutes a valuable supplement to histopathology and is suitable for use in toxicity studies.
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  • 114
    ISSN: 1432-0738
    Keywords: Alkaline elution ; 1,3-Butadiene ; Lung ; Liver ; Mouse ; Rat ; Single-strand breaks ; DNA-DNA cross-links ; DNA-protein cross-links
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The alkaline filter elution technique was used to evaluate single strand breaks (SSB), DNA-DNA (DDCL) and DNA-protein cross-links (DPCL) in liver and lung of male rats (Sprague-Dawley) and male mice (B6C3F1) after exposure to 2000 ppm 1,3-butadiene (BD) for 7 days (7 h/day and/or to 100, 250, 500, 1000) 2000 ppm BD for 7 h. SSB were detected in liver DNA of both species at 2000 ppm. Cross-links are more pronounced in mouse lung than in mouse liver. Elution rates of lung DNA from mice exposed for 7 h to different concentrations of BD revealed an increase in cross-links between 250 and 500 ppm, and a further increase in cross-links up to 2000 ppm. No such signs of genotoxicity could be observed for the lung of rats. Our data support the involvement of reactive metabolites (epoxybutene and especially diepoxybutane) in butadieneinduced carcinogenesis in the mouse but not to that extent in the rat.
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  • 115
    ISSN: 1432-0738
    Keywords: C(±)P(±)-Soman ; Toxicokinetics ; 2-(o-cresyl)-4H-1∶3∶2-benzodioxaphosphorin-2-oxide ; CBDP ; Carboxylesterase ; Rat ; Guinea pig ; Marmoset
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment of rats and guinea pigs with the specific carboxylesterase inhibitor 2-(o-cresyl)-4H-1 ∶ 3 ∶ 2-benzodioxaphosphorin-2-oxide (CBDP) reduces the LD50 of the nerve agent C(±)P(±)-soman in these species to the same range as in primates. This suggests that such CBDP-pretreated animals can be used in investigations that are relevant for prophylaxis and therapy of intoxication with C(±)P(±)-soman in primates including humans. In order to test this hypothesis we have studied the toxicokinetics of the toxic C(±)P(−)-isomers of soman in artificially respirated and CBDP-pretreated rats and guinea pigs at intravenous doses corresponding to 6 × LD50. A comparison of the areas under the curve (AUCs) of the blood levels of C(±)P(−)-soman in pretreated and non-pretreated animals at the same absolute dose shows extreme nonlinearity with dose, indicating that CBDP occupies highly reactive binding sites which are no longer available for sequestration of the soman isomers. The AUCs of C(±)P(−)-soman at equitoxic doses of 6× LD50 are reduced by pretreatment with CBDP from 1683 to 464 ng.min.ml−1 in rats and from 978 to 176 ng.min.ml−1 in guinea pigs, which is in the range of the AUC in non-pretreated marmosets at an equitoxic dose (419 ng.min.ml−1). The blood levels of the C(±)P(−)-isomers in marmosets and CBDP rats are rather similar during the first 7 min, but persist in CBDP rats for 2 h longer at toxicologically relevant levels than in marmosets. The levels of C(±)P(−)-soman in CBDP-pretreated guinea pigs are substantially lower than in marmosets for an initial period of 80 min. Nevertheless, they drop below toxicologically relevant levels approximately 50 min later than in marmosets. Evidently, one should be cautious in considering CBDP, pretreated rats and guinea pigs as substitute primates.
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  • 116
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    Archives of toxicology 67 (1993), S. 107-112 
    ISSN: 1432-0738
    Keywords: Toluene ; Ethanol ; Metabolism ; Hepatocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatocytes isolated from control, acetone- and phenobarbital-pretreated rats were used to study the metabolic conversion of toluene to benzyl alcohol, benzaldehyde, benzoic acid and hippuric acid at low (〈100 μM) and high (100–500 μM) toluene concentrations. The baseline formation rates of toluene metabolites (benzyl alcohol, benzoic acid and hippuric acid) were 2.9±01.7 and 10.0±2.3 nmol/mg cell protein/60 min at low and high toluene concentrations, respectively. In vivo pretreatment of rats with acetone and phenobarbital increased the formation of metabolites: at low toluene concentrations 3- and 5-fold, respectively; at high toluene concentrations no significant increase (acetone) and 8-fold increase (phenobarbital). Apparent inhibition by ethanol, 7 and 60 mM, was most prominent at low toluene concentrations: 63% and 69%, respectively, in control cells; 84% and 91% in acetone-pretreated cells, and 32% (not significant) and 51% in phenobarbital-pretreated cells. Ethanol also caused accumulation of benzyl alcohol. The apparent inhibition by isoniazid was similar to that of ethanol at low toluene concentrations. Control and acetone-pretreated cells were apparently resistant towards metyrapone; the decrease was 49% and 64% in phenobarbital-pretreated cells at low and high toluene concentrations, respectively. In these cells, the decrease in presence of combined ethanol and metyrapone was 95% (low toluene concentrations). 4-Methylpyrazole decreased metabolite formation extensively in all groups. Benzaldehyde was only found in the presence of an aldehyde dehydrogenase inhibitor. Increased ratio benzoic/hippuric acid was observed at high toluene concentrations. These results demonstrate that toluene oxidation may be studied by product formation in isolated hepatocytes. However, the influence of various enzymes in the overall metabolism could not be ascertained due to lack of inhibitor specificity.
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  • 117
    ISSN: 1432-0738
    Keywords: 1,3-Butadiene ; Closed-chamber technique ; 1,2-Epoxybutene-3 ; Glutathione ; Glutathione turnover ; Inhalation ; Mouse ; Pharmacokinetics ; Physiological model ; Ping-pong mechanism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The gas 1,3-butadiene (BU) is an important industrial chemical and an environmental air pollutant. BU has been shown to be a weak carcinogen in the rat but a potent carcinogen in the B6C3F1 mouse. This species difference makes risk extrapolation to humans difficult and the underlying mechanism should be clarified before meaningful risk extrapolation to humans can be made. One possible explanation for the species differences in cancer response is that there are quantitative species differences in the formation of genotoxic epoxides. To investigate this possibility a physiologically based pharmacokinetic (pbpk) model for BU together with its first reactive metabolite l,2-epoxybutene-3 (butadiene monoxide, BMO) was developed. Previously reported values on hepatic glutathione (GSH) turnover, depletion of hepatic GSH in rodents exposed to BU, and in vitro metabolic data of BU and BMO were included in the model, which incorporates intrahepatic first-pass hydrolysis of BMO and the ordered sequential, ping-pong mechanism to describe the enzyme kinetics of BMO-GSH conjugation. In vitro studies were carried out to obtain tissue: air partition coefficients of BU and BMO in rat tissue homogenates. The simulated pharmacokinetics of BU, BMO, and GSH agreed with previously published experimental observations in rat and mouse obtained in closed and open chamber experiments. According to the model, the internal dose of BMO (expressed either as the concentration in mixed venous blood or as the area under the concentration-time curve) is approximately 1.6 times higher in the mouse than in the rat for exposure to BU below 1000 ppm. At higher exposure levels, GSH depletion occurs in the mouse, but not in the rat, after about 6–9 h. This GSH depletion results in up to 2–3 times higher internal doses in the mouse than in the rat. The clear but relatively small species difference in body burdens of BMO indicated from our model can only partly explain the marked species difference in cancer response between mice and rats exposed to BU.
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  • 118
    ISSN: 1432-0738
    Keywords: Bis(tri-n-butyltin)oxide ; TBTO ; Thymus ; Epithelium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bis(tri-n-butyltin)oxide (TBTO) induces cortical atrophy in the rat thymus. We studied the potential involvement of the cortical epithelium in TBTO-induced thymotoxicity by (immuno) histology and electron microscopy. Juvenile male Wistar rats were orally intubated once with either 30 or 90 mg/kg TBTO and sacrificed 4 or 10 days later. A dose-dependent thymic atrophy occurred. Anti-keratin labelling showed epithelial cell aggregation in some animals at 10 days after exposure to 90 mg/kg TBTO, when recovery of the thymus was apparent. At the ultrastructural level, a relative shift was observed from “pale” to darker epithelial cell subtypes at the 30 mg/kg dose level, both at day 4 and day 10 after intubation. This phenomenon was not observed after exposure to 90 mg/kg TBTO. Both the altered keratin distribution and the increased electron density of the epithelium probably represent non-specific phenomena. The present morphological observations support the concept that TBTO affects the thymus via its action on lymphoid cells rather than on the epithelial compartment.
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  • 119
    ISSN: 1432-0738
    Keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin ; TCDD ; Thymus ; Epithelium ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy in the rat thymus. The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 μg/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from “pale” to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 μg/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 μg/kg dose level focal epithelial cell aggregates were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. This study indicates that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Electron microscopy reveals that the differentiation of epithelial cells is altered. In addition, epithelial cell aggregates are formed.
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  • 120
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    Archives of toxicology 67 (1993), S. 307-311 
    ISSN: 1432-0738
    Keywords: Aristolochic acid ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nephrotoxic action of aristolochic acid (AA) was investigated in female Wistar rats given single doses of 10, 50 or 100 mg/kg by gastric tube. Renal lesions developed within 3 days, the effect being dose-dependent. Histologically, there was evidence of necrosis of the epithelium of the renal tubules, and functionally, there were rises in plasma creatinine and urea together with increases in urinary glucose, protein, N-acetyl-β-glucosaminidase, gammaglutamyl transferase and malate dehydrogenase. Taking AA as an example, the aim of the present study was to consider the suitability of this model, based on a combination of histology and laboratory investigations, as a short-term test for the detection of nephrotoxic agents.
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  • 121
    ISSN: 1432-0738
    Keywords: Pharmacokinetics ; Styrene ; Diethyl dithiocarbamate ; Species scaling ; Allometric extrapolation ; Mouse ; Rat ; Man ; Closed chamber technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of styrene were investigated in male Sprague-Dawley rats and male B6C3F1 mice using the closed chamber technique. Animals were exposed to styrene vapors of initial concentrations ranging from 550 to 5000 ppm, or received intraperitoneal (i.p.) doses of styrene from 20 to 340 mg/kg or oral (p.o.) doses of styrene in olive oil from 100 to 350 mg/kg. Concentration-time courses of styrene in the chamber atmosphere were monitored and analyzed by a pharmacokinetic two-compartment model. In both species, the rate of metabolism of inhaled styrene was concentration dependent. At steady state it increased linearly with exposure concentration up to about 300 ppm; more than 95% of inhaled styrene was metabolized and only small amounts were exhaled unchanged. At these low concentrations transport to the metabolizing enzymes and not their metabolic capacity was the rate limiting step for metabolism. Pharmacokinetic behaviour of styrene was strongly influenced by physiological parameters such as blood flow and especially the alveolar ventilation rate. At exposure concentrations of styrene above 300 ppm the rate of metabolism at steady state was progressively limited by biochemical parameters of the metabolizing enzymes. Saturation of metabolism (Vmax) was reached at atmospheric concentrations of about 700 ppm in rats and 800 ppm in mice, Vmax being 224 μmol/(h·kg) and 625 μmol/(h·kg), respectively. The atmospheric concentrations at Vmax/2 were 190 ppm in rats and 270 ppm in mice. Styrene accumulates preferentially in the fatty tissue as can be deduced from its partition coefficients in olive oil∶air and water∶air which have been determined in vitro at 37°C to be 5600 and 15. In rats and mice exposed to styrene vapors below 300 ppm, there was little accumulation since the uptake was rate limiting. The bioaccumulation factor body:air at steady state (K′st*) was rather low in comparison to the thermodynamic partition coefficient body:air (Keq) which was determined to be 420. K′st* increased from 2.7 at 10 ppm to 13 at 310 ppm in the rat and from 5.9 at 20 ppm to 13 at 310 ppm in the mouse. Above 300 ppm, K′st* increased considerably with increasing concentration since metabolism became saturated in both species. At levels above 2000 ppm K′st* reached its maximum of 420 being equivalent to Keq. Pretreatment with diethyldithiocarbamate, administered intraperitoneally (200 mg/kg in rats, 400 mg/kg in mice) 15 min prior to exposure of styrene vapours, resulted in effective inhibition of styrene metabolism, indicating that most of the styrene is metabolized by cytochrome P450-dependent monooxygenases. In order to simulate chronic exposure rats and mice were exposed to 150 and 500 ppm styrene on 5 consecutive days (6 h/day). On day 6, inhalation kinetics were studied. No change in the rate of styrene metabolism was detected compared to non-pretreated controls. Intraperitoneal administration of styrene to rats and mice led to concentration-time courses in the atmosphere of the closed chamber with agreed with those predicted by the applied pharmacokinetic model. After p.o. administration of styrene to rats and mice concentration time-courses showed considerable inter-animal variability. The pharmacokinetic model was extended by a first order absorption from the gastrointestinal tract with half-lives of 0.87 h (rat) and 0.41 h (mouse) to obtain reasonable fits through the measured data. The pharmacokinetic parameters of inhaled styrene were extrapolated allometrically from rat to mouse and from rat and mouse to man. A good agreement was obtained with experimentally determined values indicating similar pharmacokinetic behaviour of styrene in these species.
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  • 122
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    Archives of toxicology 67 (1993), S. 231-236 
    ISSN: 1432-0738
    Keywords: Tributyltin ; Thymic atrophy ; Immunotoxicity ; Apoptosis ; In vivo ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tributyltin (TBT) immunotoxicity in rodent species is primarily characterised by T-lymphocyte deficiency resulting from a depletion of cortical thymocytes. In this study, bis(tri-n-butyltin) oxide (TBTO) was administered to male rats as a single oral dose of 30 or 60 mg/kg, and assessments were made of thymic cytopathology and the integrity of cellular DNA. TBTO treatment did not cause severe toxicity or overt clinical signs; however, by 48 h post-dosing relative thymus weights at 30 and 60 mg/kg were reduced to 66 and 43%, respectively, of control values. Increased DNA fragmentation was evident in thymic cell isolates (principally thymocytes) obtained from treated animals during the period of thymic involution. When DNA purified from these cells was visualised by agarose gel electrophoresis a multimeric internucleosomal fragmentation pattern, indicative of supra-physiological levels of apoptosis, was detected. Although unassociated apoptotic or necrotic thymocytes were essentially absent in cell preparations from TBTO-treated rats, significantly increased numbers of mononuclear phagocytic cells were observed. Many of these cells contained either apoptotic thymocytes, with nuclear morphologies exhibiting chromatin condensation, or cell remnants which were characterised as apoptotic bodies. Dibutyltin, which is a major metabolic dealkylation product of tributyltin, failed to significantly stimulate apoptosis when added to isolated thymocytes in vitro. Collectively, these findings suggest that activation of apoptosis contributes to TBT-induced thymocyte depletion in vivo, and indicate that it is unlikely that the metabolite dibutyltin is responsible for this effect.
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  • 123
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    European journal of pediatrics 152 (1993), S. S47 
    ISSN: 1432-1076
    Keywords: Rat ; Rabbit ; Contralateral damage ; Fertility ; Microvascular patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An experimental approach was designed to analyse the outcome of testicular autotransplantation after microsurgery of arteries with 0.3–0.6 mm diameter in two different animal species. In particular, the patency of the anastomosis of the vessels, as well as testicular histology and fertility, was studied. In rats as well in rabbits, we could not observe contralateral damage after testicular autotransplantation. With the rabbit model, we can achieve a fertility rate of 37.5%; but only when we have a good patent anastomosis. Whereas, the rat model is good for surgical training of microvascular anastomosis; the quality of the microanastomosis shows no correlation to the testicular histology of the transplanted testis.
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  • 124
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    Current genetics 23 (1993), S. 15-18 
    ISSN: 1432-0983
    Keywords: Yeast ; Rat ; Ribosomal protein ; 60S Ribosomal subunit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary This communication reports on a single-copy gene of Saccharomyces cerevisiae which is homologous to the rat ribosomal protein gene L21. The yeast and the rat genes show 59% identity in DNA sequences and in the predicted protein sequences. This yeast gene is, therefore, assumed to code for an as yet unassigned ribosomal protein (URP1). The URP1 open reading frame is 480 nucleotides long and can encode a protein of about Mr 18 200. Like most of the other known ribosomal protein genes, URP1 is interrupted by an intron in its 5′ terminal part and it is preceeded by upstream sequence elements which usually regulate transcription of these genes. Northern blot analysis reveals that the URP1 gene is actually expressed in vivo.
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  • 125
    ISSN: 1432-1335
    Keywords: Differentiation ; Leukemia cell ; Stromal cell ; Colony-stimulating factor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Differentiation of the rat myelomonocytic leukemia cell line (c-WRT-7) was investigated, by co-culture with a rat embryonic bone marrow preadipose cell line (REC A16). Co-cultivation with REC A16, or with conditioned medium from REC A16 cultures (REC-CM), induced differentiation of c-WRT-7 cells to macrophages. A soluble factor(s) produced by REC A16 appeared to be responsible for the differentiation of c-WRT-7. Because REC-CM was associated with colony-stimulating activity on murine marrow progenitors, c-WRT-7 cells were cultured with various colony-stimulating factors (CSF) and it was found that macrophage CSF (M-CSF) significantly induced differentiation of c-WRT-7. We further demonstrated that both the colonystimulating and differentiation-inducing activities of REC-CM were significantly blocked by anti-M-CSF antiserum. These results suggest that the differentiation of c-WRT-7 is due to M-CSF produced by REC A16. Co-culture of these two cell lines should provide a useful model to study the mechanisms of interaction between leukemia cells and marrow stroma.
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  • 126
    ISSN: 1433-0350
    Keywords: Pineal gland ; Glucose metabolism ; Quantitative autoradiography ; Rat ; Development ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 μmol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging.
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  • 127
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    Psychopharmacology 110 (1993), S. 280-286 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Generalization ; Antagonism ; DN ; 2327 ; Diazepam ; Buspirone ; Pentobarbital ; Pentylenetetrazol ; Benzodiazepine antagonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an operant learning lever-pressing procedure on an FR10 schedule of milk reinforcement, male Wistar rats were trained to discriminate between saline and 3 mg/kg IP DN-2327, a new anxiolytic which acts on benzodiazepine receptors, 3 mg/kg IP diazepam or 15 mg/kg IP pentylenetetrazol (PTZ). More than 80% appropriate lever responding was established after 27, 38 and 44 daily training sessions with DN-2327, diazepam and PTZ, respectively, as the training drug. Although rats trained with DN-2327 dose-dependently generalized to various doses of DN-2327 and diazepam, the cue of DN-2327 was more potent than that of diazepam: ED50 values of DN-2327 and diazepam for stimulus generalization were 0.30 and 0.66 mg/kg, respectively. These animals partially generalized to pentobarbital (1–10 mg/kg) but did not generalize to buspirone (0.1–10 mg/kg). Rats trained with diazepam dose-dependently generalized to various doses of DN-2327, diazepam and pentobarbital with ED50 values of 0.51, 0.47 and 4.5 mg/kg, respectively, but did not generalize to buspirone. In rats trained with PTZ, DN-2327 and diazepam antagonized the discriminative stimulus produced by 15 mg/kg PTZ in a dose-dependent manner with ED50 values of 0.27 and 0.83 mg/kg, respectively, but buspirone neither antagonized nor was able to substitute for the PTZ-induced stimulus. The cue of DN-2327 was antagonized by flumazenil dose-dependently as was that of diazepam. Diazepam and pentobarbital reduced the total number of responses in all animals at 10 mg/kg, and buspirone did so at more than 3 mg/kg, while DN-2327 did not affect the total number of responses from 0.1 to 10 mg/kg. In conclusion, the cue of DN-2327 is similar to and more effective than that of diazepam; moreover, it is quite different from that of buspirone. In addition, the similarity of the interoceptive stimuli of DN-2327 and diazepam may suggest that they are not related to muscle relaxant and sedative properties, since the two drugs differ in this respect.
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  • 128
    ISSN: 1432-2072
    Keywords: Conditioned place preference ; Hedonia ; Food ; Dopamine ; Neuroleptics ; Autoreceptors ; Incentive learning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Numerous data support the hypothesis that dopamine (DA) plays a crucial role in reward-related processes and in incentive learning in animals and man. The possibility that various neuroleptics exhibiting a high affinity for the dopaminergic D2 (and D3) receptors could reinforce DA transmission was studied using the conditioned place preference paradigm (CPP) in rats. This was done by examining the ability of these compounds to potentiate the reinforcing properties of food in hungry rats subjected to a version of the CPP paradigm which consisted of repeated pairings of food with a single environmental cue, the floor texture of an open field. During the test session when food was no longer available in the open field, the increase in the time spent by drug-free rats on the food-paired texture was assumed to indicate the perceived rewarding value of the food. This time was significantly lengthened when the specific D2 (D3)-receptor antagonists sulpiride (4 mg/kg), amisulpride (0.5, 1 mg/kg) or pimozide (0.03, 0.06 mg/kg) were administered before the food conditioning sessions. Larger doses of these compounds as well as haloperidol, metoclopramide and the non-specific D1-D2 antagonist, chlorpromazine, regardless of the doses tested, did not exhibit this effect, but rather reduced the food-induced CPP, an action usually associated with neuroleptics. The positive effects of amisulpride was reversed by a D1 receptor antagonist, SCH 23390 (0.01 mg/kg). These results suggest that, as with amphetamine (0.5 mg/kg), some D2-specific neuroleptics enhance the incentive value of food in a narrow range of low doses, an effect proposed to reflect a “prohedonic” property. The potentiation of the release of DA unconditionally evoked by food, through a selective blockade of the release-modulating D2-autoreceptors, could constitute the neurobiological substratum of this effect. A concomitant blockade of either D2 or D1 postsynaptic receptors, however, appeared to be sufficient to counteract such activity.
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  • 129
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    Psychopharmacology 111 (1993), S. 85-90 
    ISSN: 1432-2072
    Keywords: Phencyclidine ; Spatial learning test ; Memory disruption ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the first experiment rats with 1, 2, 3 or 4 mg/kg phencyclidine (PCP), or saline injections were tested for acquisition or retention of a cheese board spatial task (dry land version of a water maze). Results indicate that relative to controls or rats with injections of 1 and 2 mg/kg PCP, rats with 3 or 4 mg/kg PCP injections were impaired in acquisition and retention of the task as measured by increased distances traveled to find the correct food location. This impairment was primarily observed in between days but not within days performance. In the second experiment rats with 4 mg/kg PCP or saline injections were tested for memory performance of a delayed spatial matching-to-sample task. Results indicate that relative to controls rats with 4 mg/kg PCP injections were not impaired at either 1–5 or 30 s delays. It is suggested that PCP through its blocking action of the NMDA receptor mediates long- but not short-term memory for spatial location information as well as the ability to retrieve previously learned spatial location information.
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  • 130
    ISSN: 1432-2072
    Keywords: Cocaine ; Nucleus accumbens ; Sensitization ; Locomotor activity ; Conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of repeated systemic or intra-nucleus accumbens cocaine administration on locomotor activity were examined for environmental dependence. Repeated IP administration of cocaine (15 mg/kg) for 5 days in the context of a given environment increased the locomotor response to a subsequent IP cocaine challenge in that environment. However, there were no differences in the locomotor response to a subsequent IP cocaine challenge in the test chamber in subjects which had received prior repeated IP administration of cocaine in the home-cage. In a second experiment, cocaine (100 µg/side) was infused into the nucleus accumbens (NACC) daily for 5 days. This repeated administration produced increases in locomotor activity to subsequent intra-NACC cocaine infusions that were environmentally independent. In contrast to the effects of repeated IP cocaine administration, subjects which received administration of vehicle, acute cocaine, or repeated cocaine in the NACC did not differ following an IP cocaine challenge. The results from these experiments indicate that increases in the response to IP cocaine following repeated IP administration are in part environmentally dependent. Moreover, repeated intra-NACC cocaine infusions increase the responsiveness of the NACC to subsequent intra-NACC cocaine. However, local activation of the NACC alone does not appear to be adequate to produce sensitization to systemically administered cocaine.
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  • 131
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Cocaine ; Opioids ; Antihistamines ; Place preference ; Drug interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously reported that the reinforcing effects of opioids are enhanced in combination with antihistamines. In the present study, effects of opioids and antihistamines on the reinforcing effects of psychostimulants such as methamphetamine and cocaine were investigated by utilizing the conditioned place preference procedure in rats. The place preference induced by methamphetamine was enhanced in combination with either morphine or chlorpheniramine, which produced additive and potentiative effects, respectively. In contrast, although the preference for cocaine was also enhanced by combination with these two drugs, morphine caused a potentiative effect and chlorpheniramine an additive one. In other words, the reinforcing effect of methamphetamine was differentially enhanced by opioids and antihistamines as compared to that of cocaine. These results suggest that the mechanism of reinforcing effect of methamphetamine is different from that of cocaine, resembling rather those of opioids.
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  • 132
    ISSN: 1432-2072
    Keywords: Adenosine A2 receptor ; Apomorphine ; Dopamine-denervation ; Striatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ipsilateral intrastriatal administration of the specific adenosine A2a receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamido adenosine (CGS 21680), produced a dose related decrease in apomorphine-induced rotation in the unilaterally 6-hydroxydopamine-lesioned rat. This effect could be reversed by intrastriatal infusions of the A2a antagonist, 4-amino-l-phenyl[1,2,4]triazolo[4,3-a]quinoxaline (CP 66,713). However, CP 66,713 had no significant effect when infused alone, neither did it influence the response to apomorphine in the absence of CGS 21680. The possible behavioural interactions between A2a receptors and striatal ACh activity were also investigated using this model. Atropine administered intrastriatally in a dose that had no effect on the response to apomorphine reduced the inhibitory effects of CGS 21680 on apomorphine-induced turning. Naloxone also reduced the effects of apomorphine, an effect which could be prevented by the co-administration of atropine, or CP 66,713. These results indicate that adenosine agonists can modulate apomorphine-induced turning by an interaction with both cholinergic and opioidergic mechanisms in the striatum.
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    Psychopharmacology 111 (1993), S. 427-434 
    ISSN: 1432-2072
    Keywords: NMDA antagonist ; MK-801 ; D1/D2 dopamine receptors ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Blocking glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptor complex with MK-801 (0.15–0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed afterd-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1–0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reducedd-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects ofd-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced byd-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.
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  • 134
    ISSN: 1432-2072
    Keywords: Delayed matching to position ; Competitive NMDA antagonist ; Non-competitive NMDA antagonist ; Short term memory ; MK 801 ; CPP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 (dizolcipine) on short term working memory in the rat were investigated. The behavioural paradigm used was discrete trial, operant delayed matching to position, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. These delays generated an orderly “forgetting” curve in control rats, with matching accuracy decreasing from approximately 100% at 0-s delay to approximately 75% at 30-s delay. Intraperitoneal (IP) administration of CPP (10 mg/kg) produced a markeddelay dependent impairment in performance, suggesting a specific effect on short term working memory. This effect was accompanied by a minor decrease in the speed of responding, and a slight increase in the number of missed trials. Lower doses of CPP had no significant effects on either matching accuracy or sedation. In contrast, IP administration of MK 801 (0.1 and 0.2 mg/kg) caused a markeddelay independent impairment in the accuracy of delayed matching performance, suggesting a non-specific disruption of performance. A lower dose (0.05 mg/kg) of MK 801 had no significant effect on matching accuracy. The two lower doses of MK 801 increased the number of nose pokes made during the delays and tended to increase the speed of responding, suggesting a stimulant-like action. The highest dose of MK 801 had the opposite effects and also decreased the number of trials completed. The results with CPP therefore support the hypothesized role of NMDA receptors in learning and memory, and the contrasting effects of these two NMDA antagonists support previous suggestions of different behavioural effects resulting from administration of competitive and non-competitive NMDA antagonists.
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  • 135
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    Psychopharmacology 111 (1993), S. 495-498 
    ISSN: 1432-2072
    Keywords: Seizure threshold ; Electroconvulsive shock ; ECS ; Lidocaine ; GABA-ergic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC. The study demonstrates a decrease in seizure threshold to lidocaine in ECS-pretreated rats as early as 1 day and as late as 18 weeks following the last ECS, and a positive correlation between the number of ECS administered and the proportion of animals having seizures in response to the LC was found. The convulsant effect of lidocaine has been proposed to be mediated through binding on the GABA receptor-ionophore complex. Therefore this study suggests that ECS causes long-lasting, possibly permanent, changes within the GABA-ergic system.
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    Psychopharmacology 112 (1993), S. 86-92 
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; Lesion ; Operant behaviour ; Temporal differentiation ; IRT〉t schedule ; Deprivation level ; Reinforcer magnitude ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a previous experiment we found that destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways by microinjection of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei resulted in impaired acquisition of temporal differentiation under an interresponse-time-greater-than-15-s (IRT〉15 s) schedule of sucrose reinforcement. This paper reports three experiments, the results of which bear on the interpretation of that finding. In Experiment 1, 32 rats were trained for 120 sessions under the IRT〉15 s schedule; then 16 received lesions of the 5HTergic pathways and 16 received sham lesions. Comparisons of the IRT frequency distributions of the two groups showed that the lesion produced a significant reduction of the mean IRT and an increase in the dispersion of IRTs, as expressed by the coefficient of variation. Obtained reinforcement rates were significantly reduced in the lesioned group, but response rates were not significantly altered. Levels of 5HT and 5-hydroxyindoleacetic acid were markedly reduced in all forebrain areas examined, without significant change in noradrenaline and dopamine levels. The results indicate that destruction of the 5HTergic pathways disrupts performance as well as acquisition of temporal differentiation. Experiments 2 and 3 examined whether changes in deprivation level and reinforcer magnitude, which are known to affect reinforcer value, would influence temporal differentiation in a similar fashion to destruction of the 5HTergic pathways. In experiment 2, 20 rats were trained under the IRT〉15 s schedule while maintained at 80% or 90% of free-feeding body weight; the more severe deprivation condition was associated with alonger mean IRT and alower coefficient of variation. In experiment 3, 16 rats were trained under the IRT〉15 s schedule using 100 µl or 20 µl of a 0.6 M sucrose solution as the reinforcer; indices of temporal differentiation did not differ between the two conditions. These results indicate that the deleterious effect of destruction of the 5HTergic pathways upon timing behaviour is unlikely to be secondary to the motivation enhancing effect of the lesion.
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  • 137
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH 23 390 ; Raclopride ; Jumping ; Learned behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to explore further the putative differential behavioral consequences of D1 dopamine and D2 dopamine receptor antagonism, SCH 23 390 (0.01–0.12 mg/kg) and raclopride (0.12–1.0 mg/kg) were administered to two separate groups of rats that had been trained in an eight-trial-per-day format to run down an alleyway, climb a vertical rope, and run across a horizontal board to access sweetened milk. Although both drugs dose-dependently reduced the speed of task completion, only raclopride produced vigorous, maldirected jumping behavior in the floor segment of the apparatus. The number of such jumps increased with dose. This raclopride-specific jumping phenomenon may provide a new behavioral arena for investigating the functional differences between D1 and D2 receptor antagonism.
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  • 138
    ISSN: 1432-2072
    Keywords: Rat ; Behavior ; Microstructure ; Dopamine releasers ; Dopamine uptake inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of four indirect dopamine agonists,d-amphetamine (0.25–4.0 mg/kg), cocaine (2.5–40.0 mg/kg), GBR 12909 (10.0–30.0 mg/kg), and nomifensine (5.0–20.0 mg/kg), on the behavioral organization of movements in an unconditioned motor paradigm were investigated in rats. The extended scaling hypothesis using the fluctuation spectrum of local spatial scaling exponents was used to quantify the geometrical characteristics of movements. The results reveal a qualitatively similar disruption of behavioral organization by lower doses of these drugs. Specifically, rats treated withd-amphetamine (〈2.0 mg/kg), cocaine (〈20.0 mg/kg), GBR 12909 (〈20.0 mg/kg), or nomifensine (〈10.0 mg/kg) exhibited a reduced range in the fluctuation spectrum, reflecting a predominance of meandering movements with local spatial scaling exponents between 1.3 and 1.7. This reduction was accompanied dynamically by a reduced predictability of movement sequences as measured by the dynamical entropy,h. By contrast, higher doses of these drugs produced distinctly different changes in behavioral organization. In particular, 4.0 mg/kgd-amphetamine and 40.0 mg/kg cocaine increased the fluctuation range, reflecting relative increases in both straight and circumscribed movements that are interpreted as a combination of spatially extended and local perseveration. In contrast, high doses of 30.0 mg/kg GBR 12909 and 20.0 mg/kg nomifensine induced only local perseveration. High doses ofd-amphetamine, cocaine, GBR 12909 and nomifensine reduced the dynamical entropy,h, indicating an increased predictability of the movement sequences. These results suggest that the generic behavioral change induced by low doses of dopamine agonists is characterized by a reduced variety of path patterns coupled with an increased variability in sequential movement sequences. The differential effects of higher doses of these drugs may be due to their influences on other neurotransmitter systems or differential affinities for different dopamine subsystems.
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  • 139
    ISSN: 1432-2072
    Keywords: Opiates ; Discrimination learning ; Conditioned taste aversion ; Parabrachial nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 µg) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition. The data point to ascending visceral pathways (parabrachial nucleus), but not dopamine terminal fields (nucleus accumbens), as possible substrates for opiate discriminative effects. These putative discriminative substrates are distinct from the medial forebrain bundle pathways mediating the positive reinforcing effects of opiates.
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  • 140
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Intervalbisection procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventeen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei: 12 rats received sham injections. The rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and to press lever B following an 8-s presentation of the same stimulus. Both groups learnt the task rapidly and maintained 〉90% accuracy throughout the experiment. When stable performance had been attained, “probe” trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) was significantly shorter in the lesioned group than in the control group. There was no significant difference between the slopes of the psychophysical functions or the Weber fractions derived for the two groups. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour, but suggest that destruction of these pathways does not disrupt the capacity for temporal discrimination.
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  • 141
    ISSN: 1432-2072
    Keywords: Morphine drug discrimination ; Rat ; 5-HT3 receptor antagonists ; Opioid ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 5-HT3 receptor antagonists, e.g. MDL72222, ondansetron and ICS205-930, have been previously reported to block a morphine (1.5 mg/kg)-induced conditioned place preference in rats. This finding suggests that these drugs may modify the morphine discriminative stimulus which underlies place conditioning. To study this further we have examined the effects of MDL72222, ondansetron and ICS205-930 against a morphine discriminative stimulus using a two-choice, food reinforced, operant paradigm. In an attempt to provide consistency with previous place conditioning studies, a morphine training dose of 1.5 mg/kg was used in addition to a higher 3 mg/kg dose which was studied in separate animals. Stimulus control of behaviour was attained at both morphine training doses, the characteristics of each being consistent with an effect at the mu opioid receptor. Ondansetron (0.001–1 mg/kg), MDL72222 (0.1–3 mg/kg), and ICS205-930 (0.001–1 mg/kg) all failed to consistently antagonise the morphine cue at both training doses, although a mild attenuation was seen in the 1.5 mg/kg group following pretreatment with an intermediate dose of ondansetron and ICS205-930 (both 0.01 mg/kg). The present results therefore suggest hat 5-HT3 antagonists do not block a morphine discriminative state, at least in rats.
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  • 142
    ISSN: 1432-2072
    Keywords: Peptides ; Tachykinins ; Substance P fragments ; Inhibitory avoidance learning ; Conditioned place preference ; Nucleus basalis magnocellularis ; Dopamine ; Neostriatum ; Nucleus accumbens ; In vivo microdialysis ; Neurodegeneration ; Alzheimer's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinforcement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes.
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  • 143
    ISSN: 1432-2072
    Keywords: Morphine ; Behavioral activity ; Analgesia ; Rat ; Self-administration ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in μ and α2 receptor concentrations (F344/N〉WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto〉F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two-bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions.
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  • 144
    ISSN: 1432-2072
    Keywords: Amphetamine ; cis-Flupenthixol ; Nucleus accumbens ; Feeding ; Sugar ; Baseline dependent ; Circadian ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Evidence indicates that amphetamine (AMP) affects feeding in a baseline-dependent fashion and that the nucleus accumbens (Acc) is an important site of action for AMP's effects on feeding. Experiment 1 examined the contribution of Acc-dopamine (DA) mechanisms to the baseline-dependent feeding effects of a 0.125 mg/kg dose of AMP using intra-Acc administrations of cis-flupenthixol (FLU). Results showed that there was an inverse relation beetween baseline sugar intake and the feeding response to AMP, such that AMP stimulated feeding in animals with low baseline intake and inhibited feeding in animals with high baseline intake. Intra-Acc FLU administration reversed the stimulatory but not the inhibitory effect of AMP. Further, intra-Acc FLU attenuated baseline feeding in high but not low baseline feeders. Experiment 2 sought to determine whether AMP would affect feeding in a baseline-dependent manner when administered in the dark photoperiod of the rat circadian cycle, when rats do most of their feeding. To this end, rats were administered three doses (0.05, 0.1, and 0.25 mg/kg) of AMP in the dark photoperiod and the intake of sugar monitored. Results showed that in low baseline feeders, AMP stimulated intake at lowest dose and had no effect at higher doses. In high baseline feeders, AMP inhibited intake in a dose-dependent manner. Taken together, these results further establish that AMP affects feeding in a baseline-dependent fashion. Moreover, the similar effects of AMP across the light and dark photoperiods suggest that a straightforward rate-dependency interpretation is not adequate. Finally, it is speculated that Acc-DAergic activity may play a role in the observed differences in baseline intake levels and in the response to AMP.
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  • 145
    ISSN: 1432-2072
    Keywords: Dopamine ; SKF 38393 ; Quinpirole ; d-Amphetamine ; Nucleus accumbens ; Localization ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of local injections of dopamine receptor agonists into various areas within the nucleus accumbens or the medial caudate-putamen on the generation of locomotor activity were examined. Combinations of 0.32 µg/side of the dopamine receptor agonists SKF 38393 (D1) and quinpirole (D2) produced increases in locomotor activity that varied according to the rostral-caudal placement of the cannulae within the nucleus accumbens. The greatest levels of locomotion were generated by injections into a region in the caudal-central nucleus accumbens, with lower levels of activity elicited by injections into more rostral or caudal regions. A similar pattern of responses was produced by administration of the indirect dopamine agonistd-amphetamine. These results indicate that there is marked heterogeneity in the response of discrete sub-regions of the nucleus accumbens to dopamine receptor stimulation and that this heterogeneity is functionally expressed in the mediation of the locomotor effects of dopaminergic agonists.
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  • 146
    ISSN: 1432-2013
    Keywords: β-Adrenergic receptors ; Muscarinic receptors ; Cardiac hypertrophy ; Cardiac myocyte ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The beta adrenergic (βAR) and muscarinic (MR) receptors have been quantitated in parallel, using 125I-pindolol and 3H-quinuclidinylbenzilate, in a model of compensatory left ventricular (LV) hypertrophy (LVH), which developed in rats 4–6 weeks after an abdominal aortic stenosis. Since aortic banding resulted in a pronounced LVH of 62%, the results were expressed both in terms of density (fmol/mg protein) and quantity (fmol per LV). In addition, competition curves using either a specific β1-antagonist or isoproterenol or carbachol allowed the determination of the two βAR subtypes and of the low and high affinity sites (defined by the inhibitory constant K i) for both β1AR and MR. In LVH, receptor density decreased for each of total βAR, β1AR subtype, high affinity (K i 6–8nM) β1AR sites (from 26±2 to 19±3 fmol/mg protein, P〈0.05), total MR and high affinity (K i 12 nM) MR sites (from 63±6 to 40±4 fmol/mg protein, P〈0.001). The βAR and MR densities dropped in parallel so that the MR/βAR ratio remained unchanged. In sharp contrast (because the LVs were bigger) the quantities of total βAR, β1 AR subtype, β1AR high affinity sites, total MR and MR high affinity sites per LV were unmodified. Thus, in compensatory LVH the total quantity of receptors per LV was unchanged, suggesting that either both synthesis and degradation were augmented in parallel or that during the process of cardiac hypertrophy they are not regulated, i. e., that the genes encoding for the two receptors were not activated, as it has been suggested for other membrane proteins. Assuming that the high affinity sites represent the receptors coupled to the adenylyl cyclase, we also propose that the overall regulatory systems were modified beyond the level of the receptors.
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  • 147
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    Pflügers Archiv 423 (1993), S. 356-364 
    ISSN: 1432-2013
    Keywords: Erythropoietin ; Hepatocytes ; Rat ; In vitro ; Hypoxia ; Signalling ; mRNA ; RNase protection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since in juvenile rats the liver is the predominant site of erythropoietin (EPO) gene expression, we have used primary cultures of juvenile rat hepatocytes to establish an in vitro system for investigation of oxygen-dependent EPO formation. When isolated hepatocytes were incubated at reduced oxygen tensions for 18–48 h, we found increased secretion of EPO protein and elevated levels of EPO mRNA, as determined by RNase protection. This increase was maximal at 3% O2, where EPO mRNA levels after 18 h were approximately 15fold higher than at 20% O2. The increase in EPO mRNA at low oxygen tensions was specific insofar as [3H]uridine incorporation, as a measure of total RNA synthesis, was reduced by approximately 50% at 3% O2, and it appeared to involve gene transcription since it was abolished in the presence of actinomycin D (35 μM). Significant increases in EPO mRNA were also observed in cells kept at 20% oxygen in the presence of cobalt chloride (50 μM) and nickel chloride (400 μM), but EPO mRNA levels achieved under these conditions were less than 7% of those in cells incubated at 3% oxygen. No increase in EPO mRNA levels was observed in cultures incubated at 20% O2 in the presence of cyclic dibutyrylAMP (10 μM-3 mM), cyclic 8-bromoGMP (10 μM1 mM), cyclohexyladenosine (1 μM), 5′-N-ethylcarboxamidoadenosine (1 μM) and phorbol 12-myristate 13acetate (3 nM). In the presence of 10% carbon monoxide, used to block haem proteins in their oxy conformation, EPO mRNA levels in hepatocytes incubated at low oxygen tensions were reduced to 63%. Taken together, these findings indicate that oxygen-dependent control of the EPO gene in hepatocytes operates via intrinsic cellular oxygen-sensing mechanisms. Their signal transduction does not seem to occur via classical “second-messenger” pathways. A haem protein may be involved in oxygen sensing, but no conclusive evidence was obtained as to whether it is essential.
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  • 148
    ISSN: 1432-2013
    Keywords: Rat ; Renal function ; Micropuncture ; Blood gases ; Anaesthesia ; Thiopentone ; Thiobutabarbitone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thiobutabarbitone(TB, Inactin)-anaesthetised rat is an extremely widely used preparation for the study of renal function at the whole-organ and nephron levels. The recent withdrawal of TB from the market has made it essential to find an anaesthetic producing experimental conditions as similar as possible to TB to allow comparison of past and future data. Blood gas analysis, clearance and micropuncture studies were therefore performed in rats anaesthetised with TB or the related thiobarbiturate thiopentone (TP) (both 100 mg/ kg body weight) to establish whether the latter meets this requirement. Both barbiturates caused similar transient respiratory depression and acidosis. Mean values (TP versus TB) over the total 8-h observation period for glomerular filtration rate (0.94 versus 1.05 ml/min), urine flow (3.8 versus 4.4 μl/min) and K+ excretion (0.98 versus 1.18 μmol/min) were slightly lower (P〈0.05) in TP rats, whereas renal blood flow (6.26 versus 6.24 ml/min), filtration fraction (0.31 versus 0.34) and Na+ excretion (0.11 versus 0.098 μmol/min) did not differ. The single-nephron filtration rate (SNGFR) (42.1 versus 41.1 nl/min) and fractional reabsorption (42% versus 47%), both measured in the proximal tubule, did not differ, although in the TP group SNGFR rose with time (4.4%/h) whereas the fractional reabsorption did not change significantly; in the TB group SNGFR was constant but fractional reabsorption declined with time (1.5%/h). Fractional reabsorption up to the distal convoluted tubule declined with time, this was more pronounced in the TP group. SNGFR measured at this site did not differ between TP and TB (30.3 versus 30.1 nl/min) but increased with time with TP (2.7%/h). Although renal function under TP is somewhat less stable than under TB, the differences are minor and, given that the latter is also characterised by non-steady-state conditions, it is concluded that TP is a reasonable replacement for TB.
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  • 149
    ISSN: 1432-2013
    Keywords: Ryanodine ; Rat ; Fetus ; Adult ; Skinned myocardial fibers ; Caffeine ; Calcium ; Magnesium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ryanodine causes depression of the caffeine-induced tension transient (ryanodine depression) in skinned muscle fibers, because it blocks the sarcoplasmic reticulum (SR) Ca2+-release channels [Su, J. Y. (1988) Pflügers Arch 411:132–136, 371–377; (1992) Pflügers Arch 421:1–6]. This study was performed to examine the sensitivity of SR Ca2+-release channels to ryanodine in fetal compared to adult myocardium and to investigate the influence of Ca2+, caffeine, and Mg2+ on ryanodine depression in skinned fibers. Ryanodine (0.3 nM–1 μM) caused a dose-dependent depression in skinned myocardial fibers of the rat, and the fetal fibers (IC50≈74 nM) were 26-fold less sensitive than those of the adult (IC50≈2.9 nM). The depression induced by 0.1 μM or 1 μM ryanodine was a function of [caffeine], or [Ca2+] (pCa〈6.0), which was potentiated by caffeine, and an inverse function of [Mg2+]. At pCa〉8.0 plus 25 mM caffeine, a 20% ryanodine depression was observed in both the fetal and adult fibers, indicating independence from Ca2+. Ryanodine depression in skinned fibers of the fetus was less affected than that seen in the adult by pCai, [caffeine]i, or 25 mM caffeine plus pCai or plus pMgi (IC50≈pCa 4.5 versus 5.1; caffeine 12.7 mM versus 2 mM; pCa 6.7 versus 7.3; and pMg 3.9 versus 3.3 respectively). The results show that the SR Ca2+-release channel in both fetal and adult myocardium is modulated by Ca2+, caffeine, and Mg2+. It is concluded that less ryanodine depression seen in the skinned fibers of the fetus, indicating a relatively insensitive SR Ca2+-release channel, could contribute to the resistance of intact myocardium to ryanodine.
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  • 150
    ISSN: 1432-2072
    Keywords: Animal model ; Rat ; Antipsychotic ; Schizophrenia ; Latent inhibition ; Attention ; Selective attention ; Conditioned emotional response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.
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  • 151
    ISSN: 1432-2072
    Keywords: Nicotine ; Withdrawal ; Discrimination ; Activity ; Startle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three different behavioral measures were used to assess the effects of abrupt cessation of chronic nicotine treatment. Nicotine (0, 3, or 6 mg/kg per day) was continuously administered for 12 days in rats by surgically implanting Alzet osmotic mini-pumps subcutaneously. Experiment 1 employed a light/dark discrimination task. There were no significant effects on number of responses or percent correct responding either during nicotine administration, or following cessation of nicotine. Experiment 2 examined ambulatory (locomotor) and nonambulatory activity. Chronic nicotine administration produced significant dose-dependent increases in both ambulatory and nonambulatory activity during the first 3 days of exposure. However, no significant alterations were seen in activity levels following nicotine cessation. Experiment 3 examined sensorimotor reactivity using the auditory startle response. During nicotine withdrawal, significant increases were seen in startle amplitude in both nicotine groups for 4 days. Nicotine (0.4 mg/kg, IP) administered before startle testing during the withdrawal phase attenuated the increased reactivity seen during nicotine cessation. These studies indicate that 1) rats display increased sensorimotor reactivity after cessation of chronic nicotine exposure, and 2) the expression of nicotine dependence and withdrawal is dependent on the behavioral task employed.
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  • 152
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    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 77-81 
    ISSN: 1432-1912
    Keywords: Amthamine ; Histamine H2 receptors ; Gastric acid secretion ; Conscious cat ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The new histamine H2 receptor agonist amthamine, [2-amino-5-(2-aminoethyl)-4-methylthiazole], was tested for its activity on gastric acid secretion in different in vivo and in vitro experimental models. Amthamine induced a dose-related increase in acid secretion both in conscious cats with a gastric fistula (ED50 = 0.069 μmol/kg/h) and in anaesthetized rats with a lumen-perfused stomach (ED50 = 11.69 gmol/kg i.v.). In this last preparation the efficacy of amthamine was significantly higher than that of histamine and dimaprit. Amthamine was an effective secretagogue also in the rat isolated gastric fundus, behaving as a full agonist (EC50 = 18.9 μmol/l). In all the experimental models amthamine was more potent than dimaprit (from 3 to 10 fold) and approximately equipotent with histamine, and its effect was competitively antagonized by the histamine H2 receptor antagonists famotidine or ranitidine. Experiments with H1 and H3 receptor antagonists indicated that Amhamine is devoid of stimulatory activity at H1 and H3 receptors. The present data indicate that amthamine is a full agonist at histamine H2 receptors and, being more effective and selective than the other compounds of the family, it may represent a good alternative to the other available histamine H2 receptor agonists for the study of gastric acid secretion.
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  • 153
    ISSN: 1432-1912
    Keywords: CCK-A receptor ; Food intake ; Locomotor activity ; cGMP levels ; Dopaminergic cells ; Rat ; Mouse ; CCK antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of SR 27897, a potent and selective CCK-A vs CCK-B receptor antagonist (Ki = 0.2 nM on guinea-pig pancreas vs 2000 nM on rat brain) was studied on behavioural, electrophysiological and biochemical effects induced by peripheral or central injection of CCK-8S. For comparative purposes, devazepide, a reference CCK-A receptor antagonist, was investigated in these same models. CCK-induced hypophagia and CCK-induced hypolocomotion in rats, two behavioural changes associated with the stimulation of peripheral CCK-A receptors, were dose-dependently antagonized by SR 27897 (ED50 = 0.003 and 0.002 mg/kg i.p., respectively) and devazepide (ED50 = 0.02 and 0.1 mg/kg i.p., respectively). CCK-induced decrease of cerebellar cGMP levels in mice was also reduced by SR 27897 (ED50 = 0.013 mg/kg) and by devazepide (0.084 mg/kg). The CCK-induced turning behaviour after intrastriatal injection in mice, and the potentiation of the rate suppressant activity of apomorphine on rat DA neurons, were blocked by higher doses of SR 27897 and devazepide, consistent with the probable central origin of these effects. The respective ED50s were 0.2 mg/kg i.p. for SR 27897 and 4.9 mg/kg i.p. for devazepide in the former model, while the respective minimal effective doses were 1.25 and 5 mg/kg i.p. in the latter test. In most tests the i.p./p.o. ratio for SR 27897 was near unity, suggesting a high oral bioavailability of the compound. Taken together, these findings support the notion that SR 27897 behaves as a potent CCK-A antagonist able to cross the blood brain barrier.
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  • 154
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    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 638-642 
    ISSN: 1432-1912
    Keywords: Guanethidine ; Rat ; Capsaicin ; Primary afferent nerves ; Nippostrongylus brasiliensis ; Ruthenium red
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Superfusion of capsaicin onto the serosal surface of jejunum of Nippostrongylus brasiliensis-sensitized rats induces a short-lasting (1–3 min), dose-dependent (2 to 20 μg) decrease in blood pressure which ranges from −5.3±1.40% to −22.6±2.20%. The hypotension evoked by capsaicin was more marked in sensitized rats than in unsensitized animals, which responded only to the highest dose (20 mg) of capsaicin tested. The hypotensive effects of capsaicin were not affected by intravenous injections of mepyramine (10 mg/kg), a histamine receptor antagonist, or by the cycloxygenase inhibitor indomethacin (10 mg/kg). However, an intravenous injection of a platelet-activating factor (PAT) antagonist, BN 52021 (20 mg/kg), or an intraperitoneal injection of guanethidine (8 mg/kg) 18 h prior to experimentation, to functionally impair the sympathetic nerves, abolished the capsaicin-induced drop in blood pressure. Treatment of neonatal rats with capsaicin reduced by 75% the hypotensive effects of capsaicin, whereas the capsaicin antagonist, ruthenium red, reduced non-significantly the hypotensive action of capsaicin. It is concluded that the activation of jejunal sensory nerves in N. brasiliensis-sensitized rats by capsaicin induced a reflex hypotension that is dependent upon PAF release from mast cells and functional sympathetic nerves. In addition, the afferent function of the sensory nerves are not totally blocked by ruthenium red as capsaicin elicits the reflex hypotension in the presence of this blocker of sensory nerve efferent function.
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  • 155
    ISSN: 1432-1912
    Keywords: WAY-100135 ; 5-HT1A receptor antagonists ; Enantiomers ; Rat ; Superior cervical ganglion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A grease-gap extracellular recording technique was used to detect 5-HT1A receptor-mediated hyper-polarizing responses to 5-hydroxytryptamine (5-HT) in the rat isolated superior cervical ganglion. In the presence of the novel 5-HT1A receptor antagonist, WAY 100135 [N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropanamide], the responses to 5-HT were antagonised in a competitive manner with a pA2 value of 7.2 (6.9–8.5) and Schild plot slope of 1.0 (0.4–1.6), n = 20. The antagonist activity was greater in the (+) than the (−)enantiomer of WAY-100135. The pA2 value of the (+)enantiomer was 7.5 (7.2–8.0), Schild plot slope 1.2 (0.8–1.6), n = 17. In contrast the (−)enantiomer had weak antagonist activity (pA2 6.3±0.25, n = 3). No agonist activity of WAY-100135 or its enantiomers were observed in this study.
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  • 156
    ISSN: 1432-0878
    Keywords: Spinal cord ; Motoneurones ; Dorsal horn ; Neurofilament ; Phosphorylation ; Immunocytochemistry ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Neurofilament immunoreactivity was examined in spinal cords of rats and cats with antibodies to all three subunits (68 kD, 155 kD and 200 kD) and to different phosphorylation states of 200 kD. NFHP-, an antibody against non-phosphorylated 200 kD, labelled all rat neuronal perikarya but failed to labet cat neurofilaments. In both species, the perikarya and processes of motoneurones were immunoreactive for all three subunits but most dorsal horn neuronal perikarya were not immunoreactive for 68 kD and 155 kD. Motoneuronal perikarya and proximal processes showed filamentous labelling for 68 kD but not for 155 kD in the rat, while in neither species did these show labelling with RT97, an antibody against a highly phosphorylated form of 200 kD; immunoreactivity for 200 kD was present in both filamentous (probably partially phosphorylated) and non-filamentous (non-phosphorylated) forms, but in dorsal horn neurones only the latter was present. Interpretations consistent with this data are: in rat and possibly also cat, motoneuronal neurofilaments consist of a 68 kD backbone with partially phosphorylated 200 kD sidearms, with both 155 kD and 200 kD (non-phosphorylated) subunits in a non-filamentous form; this neurofilament becomes more highly phosphorylated along the proximal processes. The dorsal horn neurones probably contain 200 kD in a non-filamentous form but may lack the other subunits.
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  • 157
    ISSN: 1432-0878
    Keywords: Endocrine pancreas ; IGF-1 ; IGF-2 ; Insulin ; Glucagon ; Somatostatin ; Pancreatic polypeptide ; Man ; Dog ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Immunohistochemical techniques were used to study the occurrence and distribution of insulin-like growth factor 1 (IGF-1) and IGF-2 in the pancreas of man, dog, and rat and their possible coexistence with insulin (INS), glucagon (GLUC), somatostatin (SOM) and pancreatic polypeptide (PP). All control experiments, including pre-absorption of the antisera with synthetic peptide hormones, indicated the specificity of the immunoreactions obtained. In all species investigated, IGF-2-immunoreactivity occurred exclusively in INS-immunoreactive cells as was found by the use of consecutive sections and double immunofluorescence on identical sections. In contrast, IGF-1-immunoreactivity co-existed with GLUC-immunoreactivity. In man, singular SOM-immunoreactive cells also contained IGF-1-immunoreactivity. Thus, IGF-1 and IGF-2 can be localized by means of immunohistochemistry in the mammalian pancreas, and can be shown to occur in different islet cell populations. It is presumed that IGF-1 derived from A-cells and/or D-cells acts on the B-cells in a paracrine manner. The co-existence of IGF-2-immunoreactivity and INS-immunoreactivity in the human, rat, and dog endocrine pancreas indicates that mammalian IGF-2 and INS genes are regulated simultaneously.
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  • 158
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    Cell & tissue research 272 (1993), S. 391-394 
    ISSN: 1432-0878
    Keywords: ANP binding ; Yolk sac ; Decidua ; Maternal placental vessels ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Using in vitro autoradiography, binding sites of 125I-ANP (atrial natriuretic peptide) were localized in the rat placenta, visceral yolk sac, and decidua at 16, 18, and 20 days of gestation. There was diffuse binding over the labyrinthine region of the placenta and an intense binding over the decidual gland and visceral yolk sac. In the yolk sac, ANP localized over the cores of the villi where it may be involved with the regulation of transport across the membranes or the flow of blood through the vitelline vessels. Of particular interest was binding over the maternal blood vessels supplying the decidual region and placenta. Receptors were located on the endothelial cells and smooth muscle cells of the arteries and veins, indicating that ANP may be involved with regional regulation of blood flow to the placenta.
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  • 159
    ISSN: 1432-0878
    Keywords: Ascites hepatoma ; Adhesive factor ; Monoclonal antibody ; Cell membrane polarity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A cell surface-associated adhesive factor (AF) separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) has been highly purified by chromatography. AF is assumed to mediate the cell-cell adhesion essential to island formation of the hepatoma cells. A substance, immunologically crossreactive with AF, is present in the ascites fluid or culture medium of the AH136B cells. Because the substance is almost identical to AF in molecular weight and aggregation-promoting activity, it has been concluded that AF is released into the ascites fluid where it is concentrated. Monoclonal antibodies have been raised against AF purified from ascites fluid of AH136B cells. We have obtained a monoclonal antibody, coded MoAF-6D6, that strongly abolishes the aggregation-promoting activity of AF. When AH136B cell islands are incubated in the presence of Fab fragments of MoAF-6D6, cell detachment from the islands is evident within 24 h. Cell islands following 36-h culture show a distinct dissociation and islands completely lose their organization 48 h after culture. The dissociating effect of MoAF-6D6 is neutralized by the addition of AF. These results suggest that AF plays a significant role in the maintenance of cell islands.
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  • 160
    ISSN: 1439-6327
    Keywords: Successive selection ; Selection response ; Selection differential ; Realized heritability ; Percentage of slow twitch fibres ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extent to which muscle fibre composition was determined by the genes transmitted from parents was estimated by using successive selections of rats. A foundation population (GO) was established to carry out the selections; it consisted of 100 albino rats which were randomly chosen from heterogeneous stock. The heterogeneous stock was produced by random-mating of three strains, Wistar-Imamichi, Fischer 344 and Donryu. Successive selection for a high percentage of slow twitch fibres (% ST) was made from GO to the fourth generation (G4). The mean values of % ST changed from 50.0% in G0 to 55.6% in G4. The mean value in G4 was significantly higher than that in GO. The realized heritability in G0–G4 was calculated from the regression of selection response on the cumulated selection differential. The regression coefficient was 0.17 (SEM 0.04). The realized heritability was significantly different from 0 at the 0.05 level. We concluded that in rats about 17% of the variation of muscle fibre composition was determined by the genes transmitted from parents.
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  • 161
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    European journal of applied physiology 66 (1993), S. 445-450 
    ISSN: 1439-6327
    Keywords: High-carbohydrate diet ; Oxygen consumption ; Prolonged exercise ; Glycogen ; Liver ; Muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Whether or not a high intake of carbohydrate increases postprandial energy expenditure during exercise was studied in rats. The rats were meal-fed regularly twice a day (0800–0900 hours and 1800–1900 hours) on either a high carbohydrate (CHO) (carbohydrate/fat/protein = 70/5/25, % of energy) or high fat (FAT) (35/40/25) diet for 12 days. On the final day of the experiment, all of the rats in each dietary group were fed an evening meal containing equal amounts of energy (420 kJ · kg−1 body mass). After the meal, they were divided into three subgroups: pre-exercise control (PC), exercise (EX), and resting control (RC). The PC-CHO and PC-FAT groups were sacrificed at 2030 hours. The EX-CHO and EX-FAT groups were given a period of 3-h swimming, and then sacrificed at 2330 hours. The RC-CHO and RC-FAT groups rested after the meal and were sacrificed at 2330 hours. Total energy expenditure during the period 1.5 h from the commencement of exercise was higher in EX-CHO than in EX-FAT. The respiratory exchange ratio was also higher in EX-CHO than in EX-FAT, suggesting enhanced carbohydrate oxidation in the former. Compared with both PC-FAT and RC-FAT, the liver glycogen content of EX-FAT rats was significantly decreased by exercise. On the other hand, the liver glycogen content of both EX-CHO and RC-CHO was higher than that of PC-CHO rats. The glycogen content of soleus muscle of EX-FAT was slightly decreased during exercise, however, that of EX-CHO increased significantly. Thus postprandial energy expenditure during exercise was higher in the rats fed the CHO diet than in those fed the FAT diet, which could have been related to the increase of both liver and muscle glycogen storage during exercise in the former.
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  • 162
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    European journal of applied physiology 66 (1993), S. 451-454 
    ISSN: 1439-6327
    Keywords: Hindlimb suspension ; Fibre type composition ; HC IId isoform ; Soleus muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationship between the myosin heavy chain (HC) IId isoform and histochemically defined fibre types was investigated in the rat soleus muscle after hindlimb suspension. After 4 weeks of suspension, right and left muscles were removed and fibre type composition and total fibre number were examined by histochemical myosin adenosine triphosphatase staining sections. Myosin HC isoforms were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. After the suspension, there was a significant decrease in the percentage of type I fibres and a concomitant increase in that of type IIa fibres. However, the total number of fibres was not affected by suspension. The synthesis of HC IId isoform, which was not found in the control, and the decrease in the ratio of slow type myosin heavy chain isoform (HC I) were observed after suspension. These results would may suggest that the change of fibre type composition was caused by a shift from type I to IIa fibres after suspension. Furthermore, it could be suggested that the synthesis of HC IId isoform occurred during the stage of type shift from type I to IIa fibres.
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  • 163
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    Neurochemical research 18 (1993), S. 965-969 
    ISSN: 1573-6903
    Keywords: Rat ; dopamine ; immunocytochemistry ; HPLC-ED ; dorsal root ganglia ; sensory neurons ; blood vessels innervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that in the chick dorsal root ganglion (DRG) about 8% of neurons, belonging to both the A and B classes of sensory neurons exhibit a clear dopamine immunoreactivity. In the present study are reported the results of measurements, by mean of HPLC-electrochemical detection (HPLC-ED), of DA and of the DA metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat DRG and their central nerves. Very low levels of DA, about 10 folds lower than the levels found in the dorsal horn of the spinal cord, were found in the DRG. However the levels of DOPAC and HVA were approximately equivalent to the levels found in the cord. The immunocytochemical study performed in parallel has shown that some dopaminergic-immunoreactive fibers in the DRG are located around the blood vessels. Few dopamine-immunoreactive sensory neurons were identified in the DRG and immunoreactive fibers, not linked to blood vessels, were identified in the dorsal root nerves. The present work indicates that there is a dopaminergic innervation of the blood vessels in the rat DRG but that dopamine may also be, as in the chick, a transmitter of primary afferent fibers.
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  • 164
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    Documenta ophthalmologica 83 (1993), S. 175-180 
    ISSN: 1573-2622
    Keywords: Corneal contact lens electrode ; Electroretinogram ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The corneal contact lens electrode, because of its convenience, has replaced the cotton-wick electrode for recording electroretinograms from patients and animals such as dogs, rabbits, and cats. The cotton-wick electrode, however, remains popular for rat electroretinogram measurements because small contact lens corneal electrodes that fit rat eyes are difficult to fabricate. We prepared corneal electrodes from disposable needles for use in recording electroretinograms from rats. The electrodes were readily prepared, were inexpensive, and were used successfully in six rats.
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  • 165
    ISSN: 1435-2451
    Keywords: Orthotopic liver transplantation ; Rat ; Suture technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Lebertransplantation (LTX) bei der Ratte ist das am häufigsten untersuchte Transplantationsmodell. In der vorliegenden Studie wird die Technik der orthotopen LTX mit Nahttechnik und arteriellem Wiederanschluß über ein hepatoaortales Segment detailliert beschrieben. Die häufigste Todesursache in der Übungsphase war eine zu lange anhepatische Zeit (〉 20 min), danach beobachtete Komplikationen waren ausschließlich auf eine fehlerhafte Anastomosentechnik zurückzuführen. Der Vorteil der Nahtanastomosen liegt in der physiologischen Gefäßadaption und im Falle von einem arteriellen Wiederanschluß in dem geringeren Operationstrauma im Empfängertier. Trotz der komplizierteren Technik der Nahtanastomose im Vergleich zur Cuff-Technik können anhepatische Zeiten von weniger als 20 min erreicht werden.
    Notes: Abstract Liver transplantation (LTX) in the rat is a frequently used transplantation model. In the present study we give a detailed description of the suture technique for all anastomoses, except the bile duct, with arterialization of the transplanted liver over an aortoceliac segment to the recipient's aorta. Using this technique, we finally achieved survival rates of 80%. During the development stages, the main cause of death was an exceedingly long anhepatic time (〉 20 min); later on, complications occurred only from insufficient anastomoses. The advantage of the suture technique over the cuff technique is that a more physiological anastomosis is obtained with less trauma to the recipient when using rearterialization. Despite the complicated suture technique, the anhepatic time can be well reduced to below 20 min.
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  • 166
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    European archives of oto-rhino-laryngology and head & neck 250 (1993), S. 18-21 
    ISSN: 1434-4726
    Keywords: Inner ear ; Vestibular system ; Saccule ; Vascularization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A scanning electron microscope study of corrosion cast preparations of the vessels of the saccule was carried out in adult rats. This method shows the microvasculature of the saccule in the three-dimensional model. As a result of this technique we have been able to demonstrate a particular microvasculature of the saccule in the rat's inner ear. The main blood supply of the saccule consists of the arterioles coming from the vestibulocochlear artery entering the anterior margin of the macula sacculi. A few branches of the anterior vestibular artery enter the macula sacculi from the superior margin. The saccular vein drains the venous blood from a dense capil lary area underneath the striola to the posterior vestibular vein which eventually ends in the vein of the cochlear aquaduct.
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  • 167
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    European archives of oto-rhino-laryngology and head & neck 249 (1993), S. 470-472 
    ISSN: 1434-4726
    Keywords: Otitis media ; Tympanic membrane ; Topical phenol anesthesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study, local anesthetics were applied to the tympanic membrane (TM) of rats following experimentally evoked purulent otitis media (POM). The structure of the TM was evaluated 24 h, 2 weeks and 3 months after application of phenol to a discrete are of the right TM. The left ear was used as a control. POM induced swelling of all tissue layers of the pears tensa. The tissues were invaded by inflammatory cells and disintegrated. The fibrous layer also dissolved, leaving spontaneous perforations. However, phenol on inflamed TMs did not further alter the TM structure. These findings infer that the injurious effect of topical anesthesia on the intact TM is more or less negligible when applied to diseased TMs.
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  • 168
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    Journal of Morphology 215 (1993), S. 65-88 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Most avian muscles consist of serially arranged, overlapping fibers that do not extend the length of the muscle. This condition appears to be plesiomorphic with respect to diapsid reptiles. The presence of this serialfibered architecture is evidenced by bands of stained motor end-plates (meps) perpendicular to the columns of fibers and dividing each column into a series of “segments.” The avian pectoralis was chosen for a study of variation in the distribution of meps within a single muscle. We report the interspecific variation for 158 specimens in 63 species. We also use additional specimens to examine intraspecific variation.Setting aside hummingbirds, which have an unique and clearly derived condition, the number of mep bands along a column of fibers near the shoulder falls within a remarkably small range. The number of segments is not obviously related to phylogenetic relatedness or to any characteristic of flight or ecology and is only slightly related to size. The largest specimens do average more segments per column, but there are no trends among small to medium-sized species, suggesting that there is an upper limit to fiber length. However, the shape of the sternum and pattern of connective tissue in the pectoralis alleviate the need for additional fibers in many large birds. These findings suggest that the architecture of the avian pectoralis is subject to some as yet unexplained selection that stabilizes the number of myofibers and/or motor neurons. The findings provide few clues as to whether the significant factors are phylogenetic, functional, ontogenetic, or some combination of these. © 1993 Wiley-Liss, Inc.
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  • 169
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    Journal of Morphology 215 (1993) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 170
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    Journal of Morphology 215 (1993), S. 101-118 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Tetraodontiform fishes are characterized by jaws specialized for powerful biting and a diet dominated by hard-shelled prey. Strong biting by the oral jaws is an unusual feature among teleosts. We present a functional morphological analysis of the feeding mechanism of a representative tetraodontiform, Balistes vetula. As is typical for the order, long, sharp, strong teeth are mounted on the short, robust jaw bones of B. vetula. The neurocranium and suspensorium are enlarged and strengthened to serve as sites of attachment for the greatly hypertrophied adductor mandibulae muscles. Electromyographic recordings made from 11 cranial muscles during feeding revealed four distinct behaviors in the feeding repertoire of B. vetula. Suction is used effectively to capture soft prey and is associated with a motor pattern similar to that reported for many other teleosts. However, when feeding on hard prey, B. vetula directly bit the prey, exhibiting a motor pattern very different from that of suction feeding. During buccal manipulation, repeated cycles of jaw opening and closing (biting) were coupled with rapid movement of the prey in and out of the mouth. Muscle activity during buccal manipulation was similar to that seen during bite-captures. A blowing behavior was periodically employed during prey handling, as prey were forcefully “spit out” from the mouth, either to reposition them or to separate unwanted material from flesh. The motor pattern used during blowing was distinct from similar behaviors described for other fishes, indicating that this behaviors may be unique to tetraodontiforms. Thus B. vetula combines primitive behaviors and motor patterns (suction feeding and buccal manipulation) with specialized morphology (strong teeth, robust jaws, and hypertrophied adductor muscles) and a novel behavior (blowing) to exploit armored prey such as sea urchins molluscs, and crabs. © 1993 Wiley-Liss, Inc.
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  • 171
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    Journal of Morphology 215 (1993), S. 165-182 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The ultrastructure of the early chick embryo was investigated, using scanning (SEM) and transmission electron microscopy (TEM). Eggs were obtained from the shell gland by injecting hens intravenously with a synthetic prostaglandin or arginine vasopressin. Embryos were examined during late cleavage (stages IV-VI, Eyal-Giladi and Kochav, '76), formation of the area pellucida (stages VII-XI), and formation of the hypoblast (stages X-XIV). SEM highlighted the reduction in cell number at the underside of the embryo during formation of the area pellucida although it became apparent that the thickness of the embryo is not reduced to a single layer of cells at stage X. In addition, blastomeres at the perimeter of embryos (stages V-VI) project filopodial extensions onto a smooth membrane that separates the sub-embryonic cavity from the yolk. During hypoblast formation, epiblast cells generate stellate projections at their basal aspect, thus providing a meshwork for the advancing secondary hypoblast cells. By stage XII the epiblast was one cell thick and reminiscent of a columnar epithelium when viewed transversely. Cells of the deep portion of the posterior marginal zone were distinguished morphologically in the stage XII embryo by their many cell surface projections and ruffled appearance. Blastomeres at the perimeter of stage V-VI embryos projected filopodial extensions onto a smooth membrane which separates the sub-embryonic cavity from the yolk. This membrane is presumed to be confluent with the cytolemma. Evidence is presented demonstrating the presence of intracellular membrane-bound droplets which are hypothesised to contain sub-embryonic fluid. © 1993 Wiley-Liss, Inc.
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  • 172
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    Journal of Morphology 215 (1993), S. 245-260 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The highly terrestrial grapsids and gecarcinids and the amphibious sundathelphusids all have large, expanded branchial chambers. The lining of the branchial chambers is smooth and well vascularized, and it functions as a lung. The respiratory membrane and the cuticle lining the lung are extremely thin (200-350 nm). The blood vessels within the lung are formed from connective tissue cells supported by collagen fibres and lined by a basal lamina. The major vessels in the lung are embedded deep in the branchiostegite and lie just beneath the thick outer carapace. These vessels branch towards the respiratory membrane, where they eventually lose their connective tissue coverings to form thin, flattened lacunae directly below the respiratory epithelium. The lacunae (exchange sites) are bordered by specialized connective tissue cells, which either bear microvilli on their apical surface (fimbriated cells) or are very smooth. The respiratory circulation in the lung is very complex, with two portal systems present between the afferent and efferent systems, producing a total of three lacunal exchange beds. Portal systems increase the surface area available for gas exchange. The major distributing vessel in the lung is the branchiostegal vein, which runs along the inner margin of the branchiostegite. The main venous supplies come anteriorly from the infraorbital and ventral sinuses and posteriorly from the procardial sinus. The main collecting vessel is the pulmonary vein, which arises anteriorly and which runs around the ventral perimeter of the branchiostegite before emptying into the pericardial sinus. © 1993 Wiley-Liss, Inc.
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  • 173
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    Journal of Morphology 215 (1993), S. 301-312 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Annual fish development differs from that of other teleosts because a phase of blastomere dispersion-reaggregation spatially and temporally separates epiboly from embryogenesis. The fate of dispersed blastomeres was assessed in diblastodermic eggs of the annual fishes Cynolebias whitei and C. nigripinnis. In typical teleosts, blastomere determination and the events of primary embryonic induction occur prior to or during epiboly, so diblastodermic eggs produce partially or completely duplicated embryos. In the diblastodermic eggs of Cynolebias, the two blastoderms are completely separate from the one cell stage to the high blastula. Blastoderm fusion begins during midepiboly. By the end of epiboly, blastoderm fusion has been completed, and the deep, embryo-forming blastomeres of both blastoderms have completely dispersed and intermingled to form a single cell population. A typical annual fish dispersed blastomere phase ensues. Blastomeres reaggregate into a single mass, in which one embryo develops. When hatched, the young fish have no obvious structural or functional abnormalities. We suggest that the dispersed blastomeres of annual fish eggs are equivalent and that induction or determination takes place within the reaggregate. Alternatively, dispersed cells are partially determined but highly regulative, so that, when two populations fuse, the cells sort out according to tissue type and form a single embryo. In either instance, the formation of a single, normal embryo seems to corroborate the hypothesis that the dispersed cell phase of annual fishes is an adaptation that prevents environmentally induced developmental defects. © 1993 Wiley-Liss, Inc.
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  • 174
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    Journal of Morphology 217 (1993), S. 171-181 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In the American alligator, the jaw muscles show seven bundles of tendinous structure: cranial adductor tendon, mandibular adductor tendon, lamina anterior inferior, trap-shaped lamina lateralis, lamina intramandibularis, lamina posterior, and depressor mandibular tendon (originating from the musculus depressor mandibulae, m. pseudotemporalis, m. adductor mandibulae posterior, m. adductor mandibulae externus, m. intramandibularis, m. pterygoideus anterior, and m. pterygoideus posterior). These tendinous structures are composed of many collagen fibrils and elastic fibers; however, the distributions and sizes of the fibers in these tendinous components differ in comparison with those of other masticatory muscles. The differences of these properties reflect the kinetic forces or the stretch applied to each tendon by the muscle during jaw movements in spite of the simple tendon-muscle junctions. © 1993 Wiley-Liss, Inc.
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  • 175
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We describe the complex shapes of myomeres and myosepta in the mackerels and tunas (Scombridae: Teleostei), and we reveal the orientation of two major systems of collagen fibers in myosepta and horizontal septa with respect to points of attachment to skeleton and skin. Our goal is to identify the likely pathways of the transmission of muscle forces during locomotion. Our primary conclusions are (1) that the collagen fibers of myosepta, horizontal septa, and skin are the organs that transfer locomotor forces from the contraction of myomeres to the backbone and caudal fin during locomotion, and (2) that locomotor muscle pulls against a three-dimensional structure of tendons, septa, and skin that is kept in tension by the radial expansion of the contracting muscle. The main horizontal septum is formed by the convergence of myosepta and is likely to be the major transmitter of muscle force to the axial skeleton. The geometry of the myomeres, the position of red muscle, and particularly the geometric conformation of crossed-fiber arrays of collagen in the main horizontal septum suggest specific mechanisms for the transfer of muscle force to the backbone among scombrid fishes. Morphometrics and the construction of physical models help us to identify musculoskeletal mechanisms of locomotion, and we present two quantitative models of locomotor mechanics in fishes. © 1993 Wiley-Liss, Inc.
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  • 176
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    Journal of Morphology 217 (1993), S. 205-217 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Despite a great deal of work in recent years on the structure of reptilian eggshells, few studies have examined the structure and regulation of the female reproductive tract in the formation of eggshell components, and none have examined the entire process from ovulation to oviposition. In this study, we examined oviductal structure in the oviparous lizard, Sceloporus woodi, followed changes in oviductal structure during gravidity, and determined uterine function in the formation of eggshell components. The endometrial glands of the uterus produce the proteinaceous fibers of the eggshell membrane mainly during the first 24 hours following ovulation, and the fibers are secreted intact and subsequently wrapped around the in utero eggs. Eggshell fibers of different thicknesses are layered around each egg, ranging from an inner layer of thick fibers that gradually become thinner medially and finally forms an outer layer of densely packed particulate matter. These changes in the fibrous layer are reflected by the thickness and length of fibers released from the endometrial glands. Calcium deposition occurs from 3 days following ovulation through day 14 (oviposition) and is accompanied by cellular changes in the luminal epithelium suggestive of secretory activity. Deposition of the eggshell components within the uterus occurs on all eggs simultaneously, rather than sequentially. © 1993 Wiley-Liss, Inc.
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  • 177
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    Journal of Morphology 217 (1993), S. 219-227 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphogenesis of glandular architecture of the three lobes of prostate gland of the guinea pig, lateral, dorsal, and coagulating gland was studied from 35 days gestation to 90 postnatal days. Epithelial ductal tubules of various lobes of the gland were microdissected after treatment by collagenase and displayed two dimensionally. The number of ductal tips was counted, and the volume of the ductal network was quantified using a graphic tablet. The results show that the growth and ductal morphogenesis fall into two phases: prenatal and postnatal. The first outgrowth of prostatic buds begins at 35 days gestation (gestational length is 65 days). Ductal growth and branching continues over the next 15-20 days and by 55 days gestation, approximately 60%, 79%, and 71% of the adult number of ductal tips of the lateral and dorsal lobes and coagulating gland respectively, are formed. The figures increase to 89%, 84%, and 106%, respectively, by birth. There is little increase in number of ductal tips thereafter. Postnatal growth is accomplished mainly by elongation of existing ductal network with a little additional branching but with an increase in size (volume) of the tubules. Canalization of ductal tubules occurs prenatally in all lobes but postnatal functional cytodifferentiation takes a slightly different pace among them. Ductal morphogenesis of the guinea pig prostate gland differs significantly in time-course from that of the mouse in which ductal development occurs mainly postnatally. © 1993 Wiley-Liss, Inc.
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  • 178
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    Journal of Morphology 217 (1993) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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  • 179
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    Journal of Morphology 217 (1993), S. 229-238 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The structure and tooth attachment of the comblike teeth and denticles of the ayu sweetfish, Plecoglossus altivelis, were examined by light and scanning electron microscopy. The denticle is composed of a spoonlike crown with a spine pointed anteriorly, a triangular plate in the cervical region, and a root that curves laterally and tapers off to a point. The root apex is fused with a long thin pedicle that turns abruptly anteriad toward the jaw bone. Planes of the spine, the spoonlike crown, the triangle plate and the root of the denticle are varied, and the denticle is twisted in the region of the triangle plane.The superficial layer of the dentine is homogeneously calcified and is considered to be enameloid, because some of the inner dentinal epithelial cells in the tooth germ are columnar and possess cellular processes at their apical ends. The dentine is fibrous and fine dentinal tubules are visible in dentine treated with sodium hydroxide and observed by scanning electron microscopy. The upper half of the root is surrounded by a dense layer of collagen fibers running parallel to the tooth axis, and the lower half is encompassed by interlaced collagen fibers. The lower part of the root is open on its lingual side. The pedicle is a long rod which is homogeneously calcified and enmeshed by interlaced collagen fibers, and it curves mediad as it nears the jaw bone. The pedicles are interposed between a layer of gelatinous connective tissue and the jaw bone and terminate on the periosteum. Comparative aspects of ayu tooth morphology are discussed. © 1993 Wiley-Liss, Inc.
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  • 180
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    Journal of Morphology 217 (1993), S. 239-261 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Under the influence of juvenile hormone analogues (JHAs), termite workers are induced to differentiate into soldiers. In Reticulitermes santonensis, such induced differentiation is often incomplete, resulting in intercaste production. The morphology of the structures most affected during differentiation was analyzed descriptively and biometrically in normal workers, presoldiers, and soldiers, and in experimental intercastes. We observed that intercastes form a morphological and biometrical continuum between workers and presoldiers (presoldier intercastes), and between presoldiers and soldiers (soldier intercastes). We also compared the biochemistry of the normal individuals and of the intercastes; in contrast to workers, the intercastes possess a frontal gland secretion which differs from those of the presoldiers and soldiers. Besides intercaste characterization, we consider the mode of action of JHAs in termite differentiation. © 1993 Wiley-Liss, Inc.
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  • 181
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    Journal of Morphology 217 (1993), S. 263-271 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Microtopographic features of the various growth stages of the three free-living larval stages of the rat hookworm Nippostrongylus brasiliensis (Nematoda) were surveyed by scanning electron microscopy. These worms have a rounded anterior end and an elongated tail. Cuticular annulations were observed along the body, which also bore two ribbon-like lateral alae. Two rings of six lip-like lappets were observed around the triradiate oral opening in all larval stages. The cephalic space contained two lateral amphidial pits. The excretory pore in the third anterior part was observed in a ventral view of the larvae. No deirids were observed. The anus with a crescent-shape opening was located posteriorly. Phasmidial apertures, only observed in the third-stage larvae, opened on the lateral alae in the tail region. © 1993 Wiley-Liss, Inc.
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  • 182
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    Journal of Morphology 218 (1993), S. 347-358 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Spermatogenesis discontinues during both adult reproductive diapause and quiescence in the flightless males of Omorgus freyi. During both types of dormancy, spermatogenesis discontinuity is a dynamic process involving an uninterrupted supply of primary spermatocytes that undergoes partial development and lyses before spermatozoa can be formed. Notwithstanding this common feature, the pattern of discontinuity differs between the two kinds of dormancy. During reproductive diapause, spermatozoa and late spermatids are the first cells that lyse; after diapause break, spermatozoa are produced anew. During quiescence, in contrast, the first indication of discontinuity is the degeneration of late primary spermatocytes; spermatozoa apparently remain intact for a while but eventually degenerate as well. Therefore, males returning to sexual activity after a short period of quiescence may still have spermatozoa capable of fertilization. However, following a long period of quiescence, spermatozoa will be absent and must be produced anew, as in postdiapausing males. The existence of two different patterns of spermatogenesis discontinuity may indicate that each is controlled differently by the endocrine system, in response to the different environmental conditions inducing quiescence or diapause. Dual control of discontinuity may contribute to the high reproductive potential of these flightless beetles, under unpredictable and extreme desert conditions. © 1993 Wiley-Liss, Inc.
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  • 183
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    Journal of Morphology 215 (1993) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 184
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    Journal of Morphology 215 (1993), S. 31-49 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Statoliths of 61 Recent species representing all subfamilies of Mysidae were studied with special emphasis on internal structure. In addition 5 samples of fossil statoliths from Miocene deposits were examined. Species of Boreomysinae and Rhopalophthalminae show simple roughly spherical organic statoliths, with setae originating from the sensory cushion and anchored in the statolith with distal branches extending shortly below the surface. All other subfamilies possess mineralized statoliths of greater structural complexity, with differentiation in core and mantle, where each part may consist of up to three layers. Habitus is hemispherical to discoidal. External gross structures are dorsal tegmen, ventral fundus, and the ambitus forming the outer toroidal to semi-toroidal circumference. Setae penetrate the mantle through mineralic canals and insert on the surface of the core. As suggested by congeneric species of Schistomysis, there is no principal structural difference between statoliths mineralized with fluorite compared to vaterite. However, vaterite statoliths tend to be more often of moruloid appearance and are exceptional by showing a central conical hole (the hilum) or a central cavity in certain forms. These structures are typical of fossil calcite statoliths. In vaterite and fluorite statoliths, the mantle shows radially arranged (= spherulitic) crystal aggregates. Such arrangements are badly preserved in fossil calcite statoliths. In large extant statoliths, concentric structures, mainly in the form of superficial striation and/or concentric microstrata, are visible in coexistence with radial aggregates. Stratification is possibly due to stratified deposition of the nonmineralized gland product, while the spherulitic structure is indicative of subsequent radial growth of crystal aggregates. The structure of accessory fluorite statoliths in the statocyst of Mesopodopsis slabberi leads to the hypothesis that mantle material is formed by secretions of the caudal statocyst gland. After demineralization of fluorite, vaterite and calcite statoliths, an organic template remains showing most essential morphological features of the statolith. From this we conclude that the structure of the statolith is (almost) entirely matrix mediated. © 1993 Wiley-Liss, Inc.
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  • 185
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    Journal of Morphology 215 (1993), S. 89-100 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The amphibian tongue contains two types of papilla which are believed to function in gustation and in the secretion of salivary fluid. Scanning electron microscopy reveals that columnar, filiform papillae are compactly distributed over nearly the entire dorsal surface of the tongue of the frog, Rana cancrivora, and fungiform papillae are scattered among the filiform papillae. Microridges and microvilli are distributed on the epithelial cell surface of the extensive area of the filiform papillae. Light microscopy shows that the apex of each filiform papilla is composed of stratified columnar and/or cuboidal epithelium and its base is composed of simple columnar epithelium. Transmission electron microscopy reveals that most of the epithelium of the filiform papillae is composed of cells that contain numerous round electron-dense granules 1-3 μm in diameter. Cellular interdigitation is well developed between adjacent cells. On the free-surface of epithelial cells, microridges or microvilli are frequently seen. Between these granular cells, a small number of ciliated cells, mitochondria-rich cells and electron-lucent cells are inserted. In some cases, electron-dense granules are present in the ciliated cells. At higher magnification, the electron-dense granules appear to be covered with patterns of spots and tubules. Overall, the morphology and ultrastructure of the lingual epithelium of the three species of Rana that have been studied are quite similar, but they can be easily distinguished from those of Bufo japonicus. Therefore, it appears that lingual morphology is phylogenetically constrained among members of the predominantly freshwater genus Rana to produce uniformity of papillary structure and this morphology persists in Rana cancrivora despite the distinct saline environment in which it lives. © 1993 Wiley-Liss, Inc.
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  • 186
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    Journal of Morphology 215 (1993), S. 151-163 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: As part of an ongoing comparative study of pigment patterns and their formation in embryos and larvae of ambystomatid salamanders, Ambystoma maculatum from two differnt populations, one in the northern (New York) and one in the central (Tennessee) United States, were investigated. Scanning electron microscopy was used to study early neural crest development. Light microscopy in combination with markers for the two pigment cell types (xanthophores and melanophores) made it possible to follow pigment cell migration before the pigment cells were fully differentiated. A bilateral pigment pattern consisting of two horizontal melanophore stripes surrounding an interstripe area populated by xanthophores formed in the larvae. In both populations, some variation was present in the form of a continuum ranging from clear horizontal stripes to extreme cases with a random pattern. Unlike the other ambystomatids that have been investigated, the neural crest cells in A. maculatum do not form aggregates and no vertical bars are formed. Instead, both the pattern and its formation are very similar to what has been reported for salamandrids. If pattern formation mechanisms can act as developmental constraints we would expect the A. maculatum pattern to be the primitive condition in the Ambystomatidae, using the Salamandridae as the outgroup. There is no strong support for this when aggregate formation is used as a character and mapped onto phylogenies for the group. The aggregate formation mechanism, and the pigment pattern that it leads to, have most likely been secondarily lost in A. maculatum. © 1993 Wiley-Liss, Inc.
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  • 187
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    Journal of Morphology 215 (1993), S. 183-193 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The head, body, and tail regions of the epididymal duct (or caput, corpus, and cauda epididymis) in two healthy and sexually mature Sus domesticus males were examined by light microscopy and by scanning or transmission electron microscopy. The epididymal duct is lined with a pseudostratified epithelium with stereocilia and covered by a muscular-connective tissue sheath that is thickest in the tail region. Diameter of the epididymal duct and height of epididymal epithelium are maximal in the head region. Length of the sterocilia and spermatic density are higher in the head and body regions. Somatic cells are abundant in the tail region. The epididymal epithelium is made up of five cell types: basal cells, principal cells, clear cells, narrow cells, and basophilic cells. Abundant secretory units are observed in the supranuclear cytoplasm of columnar principal cells. Each mature secretory unit is constituted by electron-dense secretion granules covered by more than eight layers of cisternae of reticulum between which the mitochondria are intercalated. In the apical cytoplasm the isolated secretion granules become larger and less electron dense. The apical surface is covered by numerous sterocilia. Basal cells are pyramidal and less high than principal cells. The clear cells, arranged between the principal cells, are characterized by the presence of abundant vesicular elements and electron-lucid secretion granules, and by an apocrine secretory process. The narrow cells are characterized by their highly vacuolized cytoplasm. Intermediate cell typologies can be found among basal, principal, clear, and narrow cells, which could be four developmental stages of the same cell type. The basophilic cells are spheroidal and are found at different levels between the epithelial cells and in the connective tissue underlying the epithelium. © 1993 Wiley-Liss, Inc.
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  • 188
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    Journal of Morphology 215 (1993), S. 195-200 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In anuran amphibians, there is increasing evidence that exocrine glands dispersed throughout the general integument are secondary sex characters (SSC). Following the recent discovery of sexually dimorphic “breeding glands” in the dorsum of male Rana pipiens, we studied the effects of castration and testosterone treatment on the dorsal skin glands of male Xenopus laevis and R. pipiens to determine whether the dorsal breeding glands, or any other dorsal skin glands, are androgen dependent. The dorsal skin glands of X. laevis were unaffected by androgen status. By contrast, in R. pipiens, breeding, mucous, and seromucous glands responded to testosterone stimulation. Mucous glands were significantly (P 〈 0.05) larger in testosterone-treated frogs than in castrates. There was a large, but statistically insignificant, increase in the size of the dorsal breeding glands. Testosterone treatment also increased the epithelial cell height of breeding and seromucous glands (P 〈 0.05). In the skins of castrated and testosterone-treated frogs, there was a reciprocal relationship between the abundance of seromucous and breeding glands: in castrates, seromucous glands were abundant and breeding glands virtually absent, whereas in testosterone-treated frogs, breeding glands were abundant and seromucous glands less common. The total number of the two gland types was similar in both treatment groups. Glands that appeared to be intermediate in form between seromucous and breeding glands were observed in some frogs. These data suggest that seromucous glands may be the regressed form of breeding glands in the dorsal skin of R. pipiens and that the dorsal skin of R. pipiens is a SSC. © 1993 Wiley-Liss, Inc.
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  • 189
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    Journal of Morphology 215 (1993), S. 225-244 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The development and the structure of the bony scutes have been studied in a growth series of the armored catfish Corydoras arcuatus using light and electron microscopy. Fibroblast-like cell condensations appear in the dermis, in the posterior region of the caudal peduncle, and these will constitute the scute papillae. Collagen bundles of the preexisting dermis colonized by the papilla cells are remodeled and incorporated in the papilla to form, in addition to newly synthesized woven-fibered bony material, the initium of the scute. This process of formation differs from that described for the dermal papilla of an elasmoid scale. During growth, the osteoblasts surrounding the scute constitute the scute sac in which the scute grows. Parallel-fibered bone is deposited on both sides of the initium, and osteoblasts are incorporated within the scute matrix. The remodeling and incorporation of collagen bundles of the preexisting dermis is maintained during growth only in the deep, anterior region of the scute. The posterior region and the upper surface of the scute are close to the epidermal-dermal boundary. When growth slows down in the upper part of the scute, a characteristic, well-mineralized tissue, composed of thin vertical fibrils and granules and devoid of typical striated collagen fibrils, is deposited on the scute surface. A new term, hyaloine, is introduced for this nonosseous, highly mineralized layer constituting the upper part of the scute. Hyaloine shows thin electron-dense lines, which probably correspond to periodic growth arrests. The structure and localization of the hyaloine are compared to other well-mineralized, similar tissues found on the surface of the dermal skeleton in lower vertebrates. © 1993 Wiley-Liss, Inc.
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  • 190
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    Journal of Morphology 216 (1993) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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  • 191
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    Journal of Morphology 216 (1993), S. 17-27 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The reproductive process in insects may be affected by several factors, among which environmental temperature is one of the most important because of the poikilothermic condition of insects. To determine the effect of suboptimal temperature on the spermiogenic process of Triatoma infestans, males were exposed to 12°C for 10 days. In order to determine the reversibility of such alterations, males were returned to 28°C for 10 days after exposure to 12°C. Low temperature caused abnormal changes in the spermiogenic cells such as lack of spermatid orientation, general cyst disorganization, and asynchrony in the development of contiguous cysts. Highly vacuolized areas and pseudomyelinic bodies enclosing isolated or clustered vesicles of different electrodensity were also observed. At the end of the recovery time, cysts with spermatids developed synchronously. However, some presented isolated and clustered vesicles of different size and electrodensity. Some supernumerary organelles were also observed. These abnormal structures were related to processes of autophagy and phagocytosis of degenerating sexual cells. © 1993 Wiley-Liss, Inc.
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  • 192
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    Journal of Morphology 217 (1993), S. 161-170 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The spermathecae of female Eurycea cirrigera are compound alveolar glands; narrow neck tubules connect the distal bulbs to a common tube that opens onto the roof of the cloaca. The common tube and neck tubules produce apical secretory vacuoles that contain a periodic acid-Schiff (PAS)+ substance for merocrine export into the lumen. This substance is produced throughout the year, although secretory vacuoles are less numerous during the period of reproductive inactivity in the summer. When sperm are present, the product from the secretory vacuoles bathes sperm in the lumen. Sperm are in orderly arrays and never are embedded in the cytoplasm of the common tube or neck tubules. The distal bulbs do not produce PAS+ secretory vacuoles, and are actively spermiophagic as long as sperm are present. Sperm become embedded in the epithelium of the distal bulbs where lysosomes degrade sperm. © 1993 Wiley-Liss, Inc.
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  • 193
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    Journal of Morphology 218 (1993) 
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  • 194
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    Journal of Morphology 218 (1993), S. 225-236 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: An ultrastructural study of the ovary of the sessible jellyfish, Haliclystus octoradiatus, indicates that it is fundamentally different from that of other scyphozoans and is the most structurally complex within the class. Oocytes develop within a series of spherical, sac-like ovarian follicles consisting of an enlarged intercellular space between two layers of subumbrellar gastrodermis. Developing oocytes are largely restricted to a thin germinal epithelium at the periphery of each follicle and gradually migrate toward the lumen as they mature. Individual oocytes are surrounded by early germ cells and follicle-like accessory cells of presumed somatic origin. Similar folliclelike cells have not been described in the Cnidaria previously. Vitellogenesis appears to involve the combined activity of the Golgi complex and associated rough endoplasmic reticulum. Ovarian morphology may be helpful in deciphering phylogeneitc relationships within the Cnidaria. © 1993 Wiley-Liss, Inc.
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  • 195
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    Journal of Morphology 218 (1993), S. 237-247 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The term rostrate was introduced by Mortensen ('07) to describe a type of pedicellaria he found in spatangoids. These pedicellariae resemble tridentate ones but have arching valves. Unlike the main categories of echinoid pedicellariae, no clear diagnosis of the rostrate form exists. This work examines the detailed morphology of the valves of rostrate pedicellariae observed by light and scanning electron microscopy and compares the shapes and dimensions of their component parts with tridentate pedicellariae. The data reveal considerable differences between the two, which warrant the recognition of rostrate pedicellariae as a distinct form. A diagnosis is given. © 1993 Wiley-Liss, Inc.
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  • 196
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    Journal of Morphology 218 (1993), S. 257-280 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The Atlantic sharpnose shark Rhizoprionodon terraenovae (Richardson) is a small carcharhinid that is a common year-round resident along the southeast coast of the United States. It is viviparous and its embryos develop an epithelio-vitelline placenta. Females enter shallow water to give birth in late May and early June. Mating occurs shortly after parturition, and four to seven eggs are ovulated. Fertilized eggs attain the blastoderm stage in early June to early July. Separate compartments for each egg are formed in the uterus when the embryos reach 3-30 mm. Embryos depend on yolk for the first 8 weeks of development. When embryos reach 72 mm their yolk supply is nearly depleted and they shift to matrotrophic nutrition. When the embryos reach 40-55 mm, placental development begins with the vascularization of the yolk sac where it contacts the uterine wall. Implantation occurs at an age of 8-10 weeks by which time the embryos reach 70-85 mm. The expanding yolk sac engulfs the maternal placental villi, and its surface interdigitates with the villi to form the placenta. The rest of the lumenal surface of the uterus is covered by non-placental villi that appear shortly after implantation. Histotrophe production by the non-placental villi begins just after their formation. The placenta grows continuously during gestation. The egg envelope is present throughout gestation, separating maternal and fetal tissues. Embryos develop numerous appendiculae on the umbilical cord. Young sharks are born at 290-320 mm after a gestation period of 11 to 12 months. © 1993 Wiley-Liss, Inc.
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    Journal of Morphology 215 (1993), S. 51-63 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The histomorphology of the male reproductive system and surface morphology of the “peg-and-socket” in Argulus japonicus are described from serial sagittal and transverse sections and scanning electron micrographs. The prostate complex consists of a glandular part, a reservoir for storing the secretion, and an efferent duct opening into the ejaculatory duct. The openings of both the vas deferens and the prostate duct into the ejaculatory duct are guarded by sphincters. The ejaculatory ducts, which are lined by tall columnar epithelial cells, do not open into the cuticle-lined genital atrium but are blind-ending tubes. This observation and results obtained from observing live specimens, as well as the fact that no spermatophores are formed, suggest that semen could leave the ejaculatory duct only after puncturing of its walls. It is suggested that sperm transfer is accomplished in the following manner: during copulation contraction of the muscular walls of the vas deferens and prostate duct causes semen to be pumped into the ejaculatory duct, which is then closed off by sphincters and a high internal pressure is developed. When a spermathecal spine penetrates the walls of the ejaculatory duct, semen flows from the ejaculatory duct into the spermathecal vesicle due to the higher pressure in the ejaculatory duct. This mechanism is analogous to the sucking up of fluid with a hypodermic syringe. © 1993 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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  • 198
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 1-29 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Amathia vidovici (Vesiculariidae) has a lecithotrophic coronate larva. The apical disc of A. vidovici larvae is more complex than that of other vesiculariids and includes a new cell type, which may be glial-like in function. A massive nerve nodule consists only of neural processes; as no ganglia or other evidence of interneurons were found, sensory cells apparently innervate their effectors directly. Putative synaptic junctions within the nerve nodule indicate that both receptor and effector cells send processes to this neuropile. Some 44 intercoronal cells of three types, two of which are new, are interspersed among the approximately 40 coronal cells. Juxtapapillary bodies, a unique sensory complex previously known only from Bowerbankia gracilis larvae, also occur in A. vidovici. A large refractile body, which is of uncertain function and is positioned near the center of the larva, is described for the first time.A comparison of vesiculariid larvae that have been studied at the ultrastructural level reveals that larvae of Amathia vidovici and Bowerbankia gracilis are more similar to each other than either is to B. imbricata. Differences between the two Bowerbankia species, however, may reflect relative detail of their study and differences in interpretation rather than intergenic plasticity. Nevertheless. a distinctive suite of larval characteristics are shared by other members of the family Vesiculariidae, justifying a specific name - vesiculariform - for their larvae. A number of the defining characteristics of vesiculariform larvae also appear in the carnosan superfamily Victorelloidae. This finding is consistent with arguments based on adult characteristics that the Victorelloidea are ancestral to the Vesicularioidea. If this geneology is correct, one can predict that those vesiculariform traits which originated in the victorellids are plesiomorphic not only to the Family Vesiculariidae but to all sister taxa placed in the Vesicularioidea. © 1993 Wiley-Liss, Inc.
    Additional Material: 16 Ill.
    Type of Medium: Electronic Resource
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  • 199
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    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 119-149 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The pattern of onset and general rate of cranial ossification are compared in two marsupials, Monodelphis domestica (Didelphidae) and Macropus eugenii (Macropodidae). In both species a similar suite of bones is present at birth, specifically those surrounding the oral cavity and the exoccipital, and in both postnatal events follow a similar course. The facial skeleton matures more rapidly than the neurocranium, which is characterized by an extended period of ossification. Most dermal bones begin ossification before most endochondral bones. Endochondral bones of the neurocranium are particularly extended in both the period of onset of ossification and the rate of ossification. These data confirm suggestions that morphology at birth is conservative in marsupials and we hypothesize that the pattern of cranial osteogenesis is related to two distinct demands. Bones that are accelerated in marsupials are correlated with a number of functional adaptations including head movements during migration, attachment to the teat, and suckling. However, the very slow osteogenesis of the neurocranium is probably correlated with the very extended period of neurogenesis. Marsupials appear to be derived relative to both monotreme and placental mammals in the precocious ossification of the bones surrounding the oral cavity, but share with monotremes an extended period of neurocranial osteogenesis. © 1993 Wiley-Liss, Inc.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
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  • 200
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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