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  • 101
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Feeding ; Chewing ; Liquid diet ; Choice test ; Rat ; 5-HT1A receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There have been recent claims that the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits chewing and eating of solid but not liquid foods. Therefore, the effects of 8-OH-DPAT and another 5-HT1A agonist gepirone on the consumption of a liquid chow diet, by free feeding male rats, were examined. Both drugs produced a dose-dependent increase in the consumption of liquid diet during a 2 h test. The doses of 8-OH-DPAT and gepirone which increased liquid diet intake in this study were in the same range as those which were found previously to increase food pellet consumption by free feeding rats. The effects of 8-OH-DPAT were also examined in a feeding choice test in which free feeding animals were allowed to choose between food pellets and a liquid chow diet. In this test, 8-OH-DPAT significantly increased total food intake (liquid plus pellet) but had no significant effect on the consumption of either liquid or pellet diets when analysed separately. Thus, there were large individual differences in diet choice after 8-OH-DPAT injection. However, rats did not consistently choose to eat food pellets rather than the liquid diet, as would be predicted if the drug elicited chewing rather than eating. These results provide strong evidence that 8-OH-DPAT elicits a behaviourally specific hyperphagia and not chewing or gnawing.
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  • 102
    Electronic Resource
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    Springer
    Psychopharmacology 95 (1988), S. 195-199 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Scopolamine cue ; Muscarinic agonists ; Muscarinic antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of scopolamine, a potent antagonist at muscarinic receptors, were used for testing the discriminative effects of drugs known to act on cholinergic transmission. Rats were trained in a standard two-bar operant conditioning procedure with food as the reinforcer, according to a FR10 schedule. The training dose of scopolamine was progressively reduced from 0.25 mg/kg SC to the low dose of 0.062 mg/kg SC. Scopolarmine yielded an accurate discrimination in all the six rats tested. The generalization gradient resulted in an ED50 of 0.027 mg/kg. The scopolamine cue lasted for 1 h and was of central origin, since it was not mimicked by scopolamine methylbromide. The scopolamine stimulus generalized to atropine and trihexyphenidyl (respective ED50 values 2.20 and 0.21 mg/kg SC). Atropine depressed rate of responding, while trihexyphenidyl did not. Antagonism experiments with both direct agonists at the muscarinic receptor (arecoline and oxotremorine) and indirect agonists, i.e., inhibitors of the acetylcholine esterase [physostigmine and tetrahydroaminoacridine (THA)], led to inconsistent results. Increasing the doses of the agonists in order to block the scopolamine cue may be limited by their rate suppressant effect on responding. Based upon previously published results, it is suggested that the muscarinic agonist cue is more useful than the antagonist cue for investigating muscarinic transmission.
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  • 103
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    Springer
    Psychopharmacology 95 (1988), S. 231-236 
    ISSN: 1432-2072
    Keywords: Latent inhibition ; Early handling ; Haloperidol ; Amphetamine ; Male ; Female ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioral paradigm in which nonreinforced pre-exposure to a stimulus retards subsequent conditioning to that stimulus. The development of LI is considered to reflect learning not to attend to, or ignore, irrelevant stimuli. In our previous studies investigating the effects of early handling on LI, we have shown that normal LI was obtained in handled males and females, as well as in nonhandled females. In contrast, nonhandled males failed to show LI. This finding pointed to a long-term attentional deficit in nonhandled males. Since there is evidence that the development of LI is mediated by the dopaminergic system, the present experiments tested the possibility that the attentional deficit of nonhandled males may be related to a dopaminergic dysfunction. Experiment 1 tested whether the administration of haloperidol, which was shown to enhance LI in normal animals, would reinstate the LI effect in nonhandled males. Infantile handled (Days 1–22) and nonhandled male and female rats were tested in maturity in the LI paradigm, using a conditioned emotional response procedure. Experiment 2 tested the locomotor response of handled and nonhandled males to 0.3, 1 and 2.5 mg/kg d-amphetamine. Experiment 1 showed that handled males, handled females and nonhandled females showed a normal LI effect, whereas nonhandled males failed to develop LI. Haloperidol enhanced LI in all the groups, but this effect was most dramatic in nonhandled males, in which the drug reinstated LI. Experiment 2 showed that nonhandled males exhibited a reduced locomotor response to d-amphetamine.
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  • 104
    ISSN: 1432-2072
    Keywords: Amphetamine ; Circling behavior ; Asymmetry ; Pavlovian conditioning ; Sensitization ; Placebo ; Latent inhibition ; Extinction ; Reverse tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amphetamine-induced circling behavior increases over the course of repeated administration of the drug; likewise, after repeated administration of amphetamine, an injection of saline prior to placement of the rat in the test apparatus previously associated with the pharmacologic effects of amphetamine will increase circling behavior. Experiments were designed to determine if either of these effects would respond to manipulation of the temporal contiguity between the test environment and the peak effects of amphetamine. The placebo-like response, in accordance with a Pavlovian conditioned response, was reduced by prior non-reinforced exposure to the test environment and subject to extinction. In contrast, the increase in the amphetamine-induced response was entirely dependent on the test environment but not affected by latent inhibition or extinction. These and previous findings indicate that the development and expression of the placebo-like response is the result of a Pavlovian associative process. Although amphetamine sensitization is environment dependent, it does not resemble a conditioned response in other respects.
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  • 105
    ISSN: 1432-2072
    Keywords: Tachykinins ; Senktide ; Cholinergic ; Autoreceptor ; 6-Hydroxydopamine ; Yawning ; Mouth movements ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective NK-3 tachykinin receptor agonist senktide elicited yawning, chewing mouth movements and sexual arousal following subcutaneous administration (0.1–1.0 mg/kg) in the rat. These responses were not significantly affected by the dopamine antagonist haloperidol (0.03 mg/kg) or by 6-hydroxydopamine lesions of the nigrostriatal projection. In contrast, the behaviours were markedly attenuated by the peripheral and central muscarinic antagonist scopolamine (1 mg/kg), but not by the peripheral muscarinic antagonist N-methylscopolamine (1 mg/kg). These findings suggest that stimulation of NK-3 receptors produces yawning, chewing and sexual arousal by directly activating central cholinergic neurons.
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  • 106
    ISSN: 1432-2072
    Keywords: Butyrophenones ; Catalepsy ; Development ; Haloperidol ; Maturation ; Perphenazine ; Phenothiazines ; Ptosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Developing rats are far more sensitive than adults to the behavioral effects of haloperidol. The present results support the hypothesis that this change may reflect age-related changes in brain responses such as alterations in drug-receptor or drug-effector mechanisms. Dose-response studies of catalepsy and ptosis were conducted in male Sprague-Dawley rats aged 30, 56, or 100 days. Resulting dose-effect curves were approximately parallel and showed rightward shifts with highly significant progressive increases of ED50. Similar developmental decreases in drug sensitivity (3–6 ×) were found following systemic (PO or IP) administration of haloperidol or the phenothiazine neuroleptic perphenazine, which differ markedly in structure, potency, distribution, and metabolism. Age-related decreases in drug sensitivity (3–4 ×) were also found using intracerebroventricular (ICV) administration of both agents in an attempt to bypass potential “pharmacokinetic” influences. Since the age-dependent decrease in sensitivity to both neuroleptics was found during the rising phase of drug action (1st hour) and ranked: PO〉IP〉ICV, some change in absorption and distribution of both drugs may occur in addition to the apparently important maturational decrease in target-organ sensitivity indicated by the responses to direct ICV injection and by the similarity of results obtained with dissimilar agents.
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  • 107
    ISSN: 1432-2072
    Keywords: Clonidine ; Locus coeruleus ; Intracerebral infusion ; Withdrawal ; Naloxone ; Morphine ; 3-Methoxy-4-hydroxyphenylglycol (MHPG) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clonidine, an alpha-2-adrenergic agonist, suppresses signs of opiate withdrawal in animals and in man. Electrical or chemical stimulation of the nucleus locus coeruleus (LC) increases noradrenergic activity and brain concentration of the noradrenergic metabolite MHPG, and produces many signs of opiate withdrawal. Thus, clonidine's ability to attenuate withdrawal might be due to the reduction of noradrenergic neuronal activity originating in the LC, but additional alpha-2-adrenergic receptors throughout the body and other mechanisms may also play a role. The present study explored the neuroanatomical and pharmacological selectivity of alpha-2-adrenergic receptors of the LC in the anti-withdrawal action of clonidine. Experiment 1 tested the hypothesis that behavioral and biochemical measures of naloxone-precipitated withdrawal from morphine would be blocked by infusions of clonidine (0.6 or 2.4 μg/μl) into the LC. Significant reductions were observed in the occurrence of diarrhea, ptosis, weight loss and wet-dog shakes. Clonidine also reversed the naloxone-precipitated increase in hippocampus MHPG concentration. In experiment 2 subjects received an LC infusion or IP injection of a non-lipophilic alpha-2-agonist (ST-91), which does not penetrate the blood-brain barrier, or of clonidine into the dorsal parabrachial nucleus (DPB) to test the selectivity of the effects of clonidine infusions into the LC. ST-91 infusions into the LC reduced several of the observed withdrawal signs and increased others (e.g., jumping). Although peripheral injections of ST-91 attenuated some of the checked signs associated with naloxone-precipitated withdrawal, the frequency of wet-dog shakes was not reduced. ST-91 infusions into the LC, but not systemic ST-91 administration, prevented the withdrawal-induced increase in hippocampus MHPG concentration. Clonidine infused lateral to the LC into the DPB did not significantly attenuate withdrawal or reduce hippocampus MHPG levels. These results provide behavioral and biochemical evidence to support the suggestion that clonidine significantly attenuates naloxone-precipitated withdrawal through an interaction with noradrenergic neurons located in the vicinity of the LC.
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  • 108
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    Psychopharmacology 94 (1988), S. 84-91 
    ISSN: 1432-2072
    Keywords: Serotonin ; 8-OH-DPAT ; Anxiety ; Stress ; Raphe nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of a selective serotonin1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in two animal models of anxiety. Peripherally injected 8-OH-DPAT in doses ranging from 0.125 to 2.0 mg/kg did not increase black-white transitions (BWT) and black square entries (BSE) in a two-compartment exploratory test or punished responding in a test of conditioned suppression of drinking. With 2.0 mg/kg 8-OH-DPAT BSE and unpunished responding were reduced. In an investigation of the drinking time of water-deprived rats, naive or habituated to the test environment, 1.0 and 2.0 mg/kg 8-OH-DPAT increased the drinking time of naive rats but 2.0 mg/kg 8-OH-DPAT reduced that of habituated animals. In animals deprived of water for 48 h or subjected to immobilization stress for 2 h, 1.0 mg/kg 8-OH-DPAT increased BWT and BSE values in the two-compartment exploratory test. Infusions of 5 μg/0.5 μl 8-OH-DPAT in the nucleus raphe medianus increased BWT and BSE values in the exploratory test and punished responding in the test of conditioned suppression of drinking, whereas the same dose of 8-OH-DPAT injected in the nucleus raphe dorsalis had no effect on punished but suppressed unpunished responding. The effects of 8-OH-DPAT are only detectable in the appropriate experimental conditions. When injected systemically, the effects are evident when a state of arousal of the animals contributes to the overall behavioural output. 8-OH-DPAT shows effects comparable to those of established anxiolytics such as benzodiazepines and barbiturates when it is injected in the nucleus raphe medianus, but not in the dorsalis. The data support the hypothesis that brain serotonin is involved in the mechanisms mediating behavioural suppression in the presence of aversive stimuli.
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  • 109
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    Psychopharmacology 94 (1988), S. 119-125 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Cocaine ; Intraperitoneal and intravenous administration ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that pretreatment with dopamine (DA) receptor blockers disrupts the effect of intravenously (IV) and intracerebrally (ICV), but not intraperitoneally (IP) administered cocaine on place preference conditioning (PPC). The present study was undertaken to further evaluate possible differences between IV and IP cocaine PPC. To this end, several factors which may differentially influence IV and IP cocaine PPC were examined. Firstly, dose-response effects were studied. Intravenous cocaine produced PPC within a narrow dose range (0.5–2.5 mg/kg). Animals receiving IV injections of 5 and 10 mg/kg cocaine experienced convulsions and did not show PPC. For IP cocaine a 10-fold increase in dose (10 mg/kg) and twice the number of training trials was required in order to obtain PPC equal in magnitude to that with IV cocaine (0.5 mg/kg; two trials). Cocaine PPC was retained at least 1 month. Following IV cocaine preference developed for the side associated with the drug regardless of whether the conditioning was to the least or most preferred side. After IP cocaine, preference developed for the drug side only when the drug was paired with the least preferred side. Rats trained with IV, but not IP, cocaine significantly preferred the drug familiar side to a novel compartment. Preference for the IV or IP cocaine side developed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation of the cocaine PPC. The results show PPC procedure to be a valid test for evaluating rewarding properties of IV cocaine. However, they fail to show rewarding effects of IP cocaine.
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  • 110
    ISSN: 1432-2072
    Keywords: Nicotine ; Ageing ; Body weight ; Water intake ; Locomotor activity ; Exploratory behavior ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the effects of long-term treatment with nicotine on several behavioral measures (locomotor activity, exploratory efficiency, habituation, short-term and long-term memory) of young (5 months) and old (22 months) rats in a hexagonal tunnel maze, nicotine was added to the drinking water (0, 20 or 50 mg/l) for up to 131 experimental days. With the exception of effects on exploratory efficiency, young and old rats did not differ in their response to the drug. Nicotine decreased body weight throughout the experiment. Nicotine treatment reduced water intake during the first 30 min of the daily 4.5 h access to drinking water. Nicotine increased locomotor activity throughout the experiment. When nicotine treatment was discontinued during a 7-day withdrawal period, locomotor activity immediately dropped to control values. Intertrial habituation was not affected by nicotine. Long-term nicotine treatment had an attenuating effect on exploratory efficiency in young rats; however, the drug did not influence performance in tasks measuring spatial memory. Finally, age increased weight, decreased locomotor activity and impaired exploratory efficiency and short-term memory. Age, however, did not affect the performance of the long-term memory task.
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  • 111
    ISSN: 1432-2072
    Keywords: μ, δ opioid receptors ; Inhibition of enkephalin catabolism ; Nucleus accumbens ; Nucleus caudatus ; Motor behavior ; Kelatorphan ; DAGO ; DTLET ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of selective agonists for δ opioid receptors: [D-Thr2, Leu5]-enkephalyl-Thr6 (DTLET) and μ receptors: [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO) and of (R)-3-(N-hydroxyl-carboxamido-2-benzylpropanoyl)-L-alanine (kelatorphan), a complete inhibitor of enkephalin degrading enzymes, on the motor activity of rats was examined after their local administration into the nucleus accumbens (NA) or nucleus caudatus (NC). In both structures DTLET dose dependently enhanced locomotor activity as measured in the open-field test. This strong effect was reversed by the selective δ antagonist: ICI 174,864. Contrastingly, DAGO induced hypoactivity followed by hyperactivity 150 min later. This biphasic effect was blocked by systemic injection of naloxone, but not by ICI 174,864. The physiological relevance of these effects was ascertained by the naloxone-reversible stimulatory responses induced by kelatorphan, supporting a role for endogenous enkephalins in the control of behavior through δ receptor stimulation.
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  • 112
    ISSN: 1432-2072
    Keywords: Alcohol drinking ; Brain amines ; Neonatal ; Open field ; Porsolt's swim test ; Propranolol ; Rat ; Sleep ; Spontaneous alternation ; Startle reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effects of early postnatal treatment with a beta-adrenoceptor antagonist propranolol (5 mg/kg IP daily) on concomitant and subsequent behavior and central aminergic transmission in rats. During propranolol exposure from the 7th to the 20th postnatal days sleep-wake recordings, carried out with the static charge sensitive bed (SCSB) method, showed a decrease in the percentage of active sleep and an increase in waking. When the animals were 1–3 months of age, the open field behavior was changed, immobility time in the Porsolt's swim test was lengthened, and voluntary alcohol consumption was increased in the propranolol-treated rats. Neither motor reactivity to auditory stimuli nor spontaneous alternation behavior was affected. At the age of 4 months concentrations of brain amines and their metabolites were measured from several brain regions. In the propranolol-treated rats the noradrenaline levels were increased in the limbic forebrain and cerebellum. The results suggest that in rats the exposure to propranolol during the rapid growth period of cerebral catecholamine systems, and the concomitant alterations in sleep are related to later changes in behavior and to increased noradrenaline content in the limbic forebrain and cerebellum.
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  • 113
    ISSN: 1432-2072
    Keywords: Rat ; Dopamine receptors ; PHNO ; SKF 38393 ; Feeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of selective D-2 and D-1 dopamine (DA) receptor agonists on food consumption were investigated in free-feeding rats. A selective D-2 receptor agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), increased the consumption of standard food pellets in the dose range of 7.5–120 μg/kg, while SKF 38393 (5.0 mg/kg), a selective D-1 receptor agonist, decreased food pellet intake. The increase in food pellet intake produced by PHNO was blocked by haloperidol (an antagonist relatively selective for the D-2 receptor at the dose used, 0.05 mg/kg) and SCH 23390 (20 μg/kg, a D-1 receptor selective antagonist). Increasing “arousal” by disturbance associated with repeated food weighting also increased food pellet consumption, but did not diminish PHNO-elecited feeding. However, the same range of doses of PHNO (7.5–120 μg/kg) which increased food pellet intake decreased consumption of a liquid diet, and had no overall effect on a highly palatable liquid diet. The increase in consumption of solid food induced by PHNO appears to be secondary to enhancement of chewing behaviors. In contrast, the decrease in food intake induced by SKF 39393 may be due to a direct action of the drug on neural feeding mechanisms.
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  • 114
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    Psychopharmacology 94 (1988), S. 227-231 
    ISSN: 1432-2072
    Keywords: Adrenaline ; Naloxone ; Passive ; Avoidance ; Retention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible involvement of endogenous opioid peptides in the development of the facilitatory effect of adrenaline on memory has been investigated. For this purpose post-training administration of adrenaline and/or naloxone was carried out in rats tested in an inhibitory avoidance paradigm and subjected or not to pre-training (extensive familiarization with the training situation prior to the acquisition trial). Adrenaline injected subcutaneously in a dose of 500 μg/kg facilitated retention performance in rats both subjected or not to pre-training. Naloxone administered SC (400 μg/rat) did not influence retention behaviour in rats subjected or not to pre-training, nor did ICV (0.80 ng/rat) administration. Interestingly, the opiate antagonist when injected SC (400 μg/rat) prevented the facilitatory effect exerted by adrenaline in pretrained as well as in not pre-trained rats. However, ICV administration of naloxone (0.80 μg/rat) dit not influence the behavioral effects exerted by the bioamine. These data suggested a role of endogenous opioid peptides on the facilitatory effect of adrenaline on memory, possibly independent of novelty factors and thus of the brain β-endorphin system. In addition, our results point to the periphery as the most likely site for such interaction.
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  • 115
    ISSN: 1432-2072
    Keywords: Dopamine ; Self-administration ; (+) Amphetamine ; Amygdala ; Nucleus accumbens ; 6-OHDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 6-OHDA lesions of dopamine terminals within the amygdala were investigated on i) (+) amphetamine-induced locomotor hyperactivity and ii) the acquisition of intravenous self-administration of (+) amphetamine. The lesioned rats exhibited increased locomotor activity in response to (+) amphetamine (0.75 and 1.5 mg/kg), but not at the higher dose (3 mg/kg). Self-administration of (+) amphetamine was also significantly greater than in controls. Biochemical analysis of the 6-OHDA-induced lesions of the amygdala indicated increased turnover of dopamine (DOPAC/DA) in the nucleus accumbens. We hypothesize that the behavioural effects were mediated by amygdala-accumbens interactions.
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  • 116
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    Psychopharmacology 94 (1988), S. 254-258 
    ISSN: 1432-2072
    Keywords: Anorexia ; Feeding ; Hyperphagia ; Morphine ; Naltrexone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The delayed suppression of feeding caused by morphine was investigated in the rat. A single injection of morphine evoked a triphasic influence on feeding: a brief (1 h) severe anorexia was followed by hyperphagia (3 h) and a mild (20%) yet persistent (4–24h) anorexia. This latter anorexic effect was at least partially naltrexone reversible, and the duration of this antagonism (8 h) was longer than that of naltrexone's anorexic effect (4 h). Delayed morphine anorexia cannot be ascribed to morphine's initial stuporific influence, and it was not dependent upon previous feeding or deprivation. It was not due to gastric distension. The specificity and significance of this anorexia is discussed.
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  • 117
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    Psychopharmacology 94 (1988), S. 248-253 
    ISSN: 1432-2072
    Keywords: Bremazocine ; EKC ; Forward locomotion ; Grooming ; Open field ; Rat ; Rearing ; Tifluadom ; U-50,488H
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An observational analysis of the effects of four kappa-opioid agonists on forward locomotion, rearing and grooming displayed by rats in a novel open field was undertaken. The doses of agonists used corresponded to those previously found to produce changes in food consumption. Ethylketocyclazocine (0.1 and 1 mg/kg), bremazocine (0.01 and 0.1 mg/kg) and tifluadom (0.3 and 3 mg/kg) exerted suppressant effects on all the activities monitored. Grooming behaviour appeared to be particularly sensitive to this action, being virtually abolished by the larger doses of these compounds. In contrast, the selective kappa agonist U-50,488H (0.1–3 mg/kg) only attenuated grooming at the two highest doses tested (1 and 3 mg/kg). None of the agonists tested produced stimulation of open field activity during the 1-h study. Reductions in activity occurred at doses previously found to increase and decrease food intake. It was therefore concluded that the hyperphagia induced by kappa agonists was not part of a more general behavioural activation, whilst reductions in food consumption probably result from a non-specific behavioural depression.
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  • 118
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    Psychopharmacology 94 (1988), S. 359-364 
    ISSN: 1432-2072
    Keywords: Serotonin synthesis ; Dopamine synthesis ; RU-24969 ; Anxiety ; Antidepressant activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The regional brain synthesis of serotonin (5-HT) and dopamine (DA) was studied in rats after various doses of 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969), a 5-HT1 receptor agonist. The potential anxiolytic and antidepressant properties of the compound were examined as well. RU-24969 0.62 mg/kg significantly reduced 5-HT synthesis in the nucleus accumbens and hypothalamus, while with 1.25 and 2.5 mg/kg the effect was also seen in striatum, hippocampus, brainstem and cortex. RU-24969 2.5 and 5 mg/kg had no effect on DA synthesis in the striatum, while 5.0 mg/kg significantly increased it in the nucleus accumbens. At doses of 2.5 and 5.0 mg/kg the drug increased the motor activity of rats measured during 1 h in activity cages while 0.625 and 1.25 mg/kg had no effect. Doses ranging from 0.62 to 2.5 mg/kg RU-24969 significantly reduced unpunished responding in a test of conditioned suppression of drinking. Doses of 1.25 and 2.5 mg/kg also reduced punished responding. Finally, of various doses only 2.5 mg/kg RU-24969 significantly reduced the duration of immobility of rats in the forced swimming test but the effects were due to running around the cylinder rather than to escape attempts. In conclusion, RU-24969 reduced 5-HT synthesis in all brain areas examined, with a preferential effect for the nucleus accumbens and the hypothalamus. At higher doses, there was also a specific increase in DA synthesis in the nucleus accumbens. The compound raised the level of activity of rats but no clear evidence of any potential anxiolytic or antidepressant properties has been obtained.
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  • 119
    ISSN: 1432-2072
    Keywords: R(−)-2,5-Dimethoxy-4-77Br-amphetamine ; Rat ; 5-Hydroxytryptamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract R(−)-2,5-Dimethoxy-4-77Br-amphetamine [77Br-R(−)DOB], a radioligand of high specific activity (1500±200 Ci/mmol), was used to label membrane-associated recognition sites in rat brain. 77Br-R(−)DOB sites were of high affinity (K D=0.19 nM) but low density (B max=0.32 pmol/g tissue) in rat brain preparations. Competition experiments show that both 5-hydroxytryptamine (5-HT) and 5-HT2 antagonists display nanomolar potency for these sites. We conclude that 77Br-R(−)DOB labels 5-HT recognition sites in rat brain which do not fit into current classifications of 5-HT binding subtypes. This finding may be of aid in deciphering the mechanism of action of hallucinogens in man.
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  • 120
    ISSN: 1432-2072
    Keywords: Electroconvulsive shock ; 5-HT transporter complex ; β-Adrenoceptor ; [3H]-Paroxetine ; [3H]-Imipramine ; [3H]-Dihydroalprenolol ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of repeated electroconvulsive shock on the 5-HT uptake site were studied in rat cortex using [3H]-paroxetine binding. This ligand was used because it is thought to directly label the 5-HT uptake site, whereas [3H]-imipramine may bind to a presynaptic recognition site different from the uptake site. No changes were found in the maximum number of [3H]-paroxetine binding sites and equilibrium dissociation constant after repeated electroconvulsive shock, whereas a parallel investigation of β-adrenoceptor binding showed the expected decrease in receptor number.
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  • 121
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    Psychopharmacology 95 (1988), S. 151-156 
    ISSN: 1432-2072
    Keywords: Apomorphine ; Amphetamine ; Strychnine ; Yohimbine ; Acoustic startle reflex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were presented with noise bursts alone or noise bursts 60 ms after presentation of either a 60 dB or an 80 dB prepulse after injection of the dopamine agonists apomorphine (3 mg/kg) or d-amphetamine (4 mg/kg), the glycine antagonist strychnine (1.5 mg/kg) or the α2 antagonist yohimbine (5 mg/kg). Presentation of prepulses inhibited startle, with greater inhibition following an 80 dB versus 60 dB prepulse. Apomorphine, d-amphetamine and strychnine increased overall startle levels but did not attenuate prepulse inhibition, since the absolute change in startle following prepulse presentation was significantly greater after administration of these drugs. A lower dose of apomorphine also increased startle but had no effect on prepulse inhibition using test intervals of 10, 60, 100, 200 or 1000 ms. While these drugs did decrease per cent prepulse inhibition, this seemed wholly attributable to their increasing overall startle levels, rather than a real attenuation of prepulse inhibition. Yohimbine did not alter either startle baseline or prepulse inhibition. The results do not support the conclusion that overactivity of dopamine systems attenuates prepulse inhibition and, in addition, suggest that prepulse inhibition does not result from activation of either glycine or norepinephrine projecting to α2 adrenergic receptors.
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  • 122
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    Psychopharmacology 96 (1988), S. 281-284 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Oral administration ; Transdermal administration ; Nicotine ; Cytisine ; Arecoline ; Mecamylamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a standard two-lever drug discrimination paradigm, rats were trained to discriminate nicotine 0.5 mg/kg PO from saline. Injections occurred 15 min before the session. Subjects reached the training criterion in a mean of 38 sessions. Nicotine PO, SC, and IP generated similar dose-effect curves (ED50=0.073 mg/kg PO, 0.076 mg/kg SC, 0.090 mg/kg IP); the dose-effect curve for transdermal (TD) administration fell approximately 1 log unit to the right (ED50=1.34 mg/kg). The percentage of rats choosing the nicotine-appropriate lever peaked at 15 min and gradually decreased to 50% or less by 180 min for nicotine PO and TD, a time-decay function similar to that previously shown for SC administration. The nicotinic cholinergic agonist cytisine (0.5–8.0 mg/kg) PO and TD produced up to 56% nicotine-appropriate responding, while the muscarinic cholinergic agonist arecoline (1.0–4.0 mg/kg) PO and TD produced only saline-appropriate responding. The nicotine cue did not generalize to the cholinergic antagonist mecamylamine (0.125–0.5 mg/kg) PO or TD; mecamylamine 0.5 mg/kg PO but not TD completely blocked the PO and TD nicotine cues. These results show that an approximately equal cue occurs with PO, IP, and SC administration, and that the TD cue is considerably weaker. The significance of the procedure as an animal analog of human transdermal nicotine intake is discussed.
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  • 123
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    Psychopharmacology 96 (1988), S. 311-316 
    ISSN: 1432-2072
    Keywords: Rat ; Neuroleptics ; Catalepsy ; Dopamine receptors ; Muscarinic receptors ; SCH23390 ; Pilocarpine ; Atropine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an attempt to understand the nature of the interactions between D1 and D2 dopamine subsystems as well as between dopamine and acetylcholine, catalepsy was assessed in rats following various drug treatments. The D1-specific antagonist SCH23390 (0.1 mg/kg) produced prompt, potent and brief (〈90 min) catalepsy with an ED50 of 0.105 mg (0.3 μmol)/kg. Conversely, fluphenazine (0.1 mg/kg), spiroperidol (0.1 mg/kg), and haloperidol (0.2 mg/kg) all had comparably potent but more slowly rising and prolonged (〉240 min) effects. The action of SCH23390 was synergistic with spiroperidol, inhibited by apomorphine or atropine, unaffected by mecamylamine, and markedly potentiated by pilocarpine. However, pilocarpine was unable to significantly potentiate the action of fluphenazine or spiroperidol. It is inferred that SCH23390 differs from the classical neuroleptics in its mechanism of cataleptogenicity, that there is a cholinergic link with the D1 dopamine system, and further, that there may be a difference in the nature or impact of the cholinergic interaction with the D1 and D2 dopamine systems.
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  • 124
    ISSN: 1432-2072
    Keywords: Enkephalin ; Ventral mesencephalon ; Investigatory behaviour ; Motor behaviour ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mesolimbic dopamine (DA) system, originating in the ventral tegmental area and projecting to limbic forebrain regions, plays a crucial role in mediating several important aspects of behaviour. Proximal to these DA neurons are enkephalin-containing nerve fibers. In an attempt to characterize the behavioural role of enkephalinergic transmission in the VTA, the present experiment examined in detail the investigatory and motor responses to microinfusion of d-ala-met-enkephalin (DALA), a long lasting analogue of enkephalin, into the ventral tegmental area (VTA). Injections into the substantia nigra (SN) and the hippocampus (HPC) were also performed as controls for site specificity. The behavioural apparatus consisted of an eight-hole box monitored by a video camera. Four doses of DALA were injected in the VTA (0.05, 0.1, 1 and 2.5 μg/μl bilaterally in 1 μl volume) and one dose in the SN and HPC (0.1 μg/μl bilaterally in 1 μl volume). The effect of DALA injections in the VTA was characterized by an inverted U-shape dose-effect curve. The low doses (0.05 and 0.1) induced an increase in the frequency of hole visits accompanied by a decrease in the mean duration of visits, whereas the highest doses induced a decrease in hole visit frequency. Low doses of DALA had no effect on strategy or organization of exploration, whereas the high doses produced decreased switching between holes. After low doses of DALA, locomotor activity at the periphery of the testing box was not significantly affected but locomotor activity in the centre was increased. After high doses of DALA, locomotor activity in the center and at the periphery of the box were decreased. Frequency of rearing was either not affected or decreased by DALA treatment. DALA injected in the SN resulted in a small increase in frequency of hole visits and did not affect rearing and locomotor activity. DALA injection in the HPC had no effect on investigatory and spontaneous motor behaviour. The results are discussed in terms of a modulatory role of endogenous enkephalin on mesolimbic dopamine neurons.
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  • 125
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    Pflügers Archiv 413 (1988), S. 62-66 
    ISSN: 1432-2013
    Keywords: Erythropoiesis ; Erythropoietin ; Renal artery constriction ; Hypoxia ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoictin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.
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  • 126
    ISSN: 1432-2013
    Keywords: Chloride channel ; Rat ; Skeletal muscle ; Stereoisomers ; 2-(p-chloro-phenoxy) isobutyric acid ; Clofibric acid ; Myotonia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The S-(−) isomers of a series of clofibric acid analogs produced only a block of chloride conductance of rat skeletal muscle fibers with increasing concentrations until block was nearly complete. The R-(+) isomers, on the other hand, at low concentrations increased chloride conductance by as much as 9% to 39% and at higher concentrations decreased chloride conductance, but never by more than 27% of the control value. The actions of the enantiomeric pairs to either produce or inhibit myotonic excitability paralleled their ability to block or increase chloride conductance, respectively.
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  • 127
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 96-98 
    ISSN: 1432-1912
    Keywords: Histamine ; Gastric acid secretion ; Central nervous system ; Vagus nerve ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Administration of 10–100 μg of histamine into the lateral cerebral ventricle of anaesthetized rats stimulated gastric acid secretion in a dose-dependent manner, while subcutaneous (s. c.) injections of the same doses produced clearly less pronounced increases in the acid output. In vagotomized rats only a marginal response to histamine given into the lateral ventricle was observed. When injected into the third cerebral ventricle the doses of histamine needed for the stimulation of gastric acid secretion were 1–10 μg, the effect being totally abolished by vagotomy. The results indicate that histamine is capable of stimulating gastric acid secretion by a central, vagal-dependent mechanism.
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  • 128
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 345-349 
    ISSN: 1432-1912
    Keywords: 5-HT ; Tryptophan hydroxylase ; Sex difference ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a sex difference in central tryptophan hydroxylase capacity. Hence, both sexes received a high dose of l-tryptophan (400 mg/kg), which resulted in a tenfold increase in brain tryptophan concentrations and presumably a virtual saturation of tryptophan hydroxylase. Following such treatment, 5-hydroxytryptophan (5-HTP) levels, measured after l-amino acid decarboxylase inhibition, were compared in males and females. Both in saline-and l-tryptophan-treated rats, 5-HTP levels were generally higher in females. In another group of animals, receiving 400 mg/kg of l-tryptophan as sole treatment, 5-HT and 5-HIAA concentrations were measured. As in the case of 5-HTP, the higher 5-HT and 5-HIAA levels observed in females persisted after l-tryptophan treatment. The present data suggest that brain tryptophan hydroxylase activity is greater in females; this sex difference probably contributes to the higher 5-HT and 5-HIAA levels in females.
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  • 129
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    Cell & tissue research 252 (1988), S. 57-66 
    ISSN: 1432-0878
    Keywords: Heart ; Endothelium ; Tracer studies ; Junctional structures ; Permeability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The isolated perfused heart model was used to examine the structure of rat cardiac capillaries and their permeability to macromolecules of various sizes. Haemoglobin (diameter 6.4 nm) and catalase (10.4 nm) did not cross the endothelium but remained on the luminal side. Cytochrome C (3 nm) and horseradish peroxidase (6 nm) both crossed the endothelium to the subendothelial space and filled the caveolae on the abluminal side as well as the entire length of the lateral intercellular spaces. The membranes of the endothelial cells are separated by an intercellular gap of mean width 18.2 nm. At one or more zonular regions within each lateral intercellular space the two membranes approach each other more closely and frequently appear to fuse. However, tilting the specimen shows that, in these regions, there is a gap of mean width 5.4 nm (in lanthanum- and tannic acid-treated tissue, 3.8 nm in ferrocyanide-treated tissue) between the membranes. We conclude that these narrow regions sieve macromolecules on the basis of size although other factors may determine their permeability properties.
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  • 130
    ISSN: 1432-0878
    Keywords: Uterus ; Intraepithelial lymphocytes ; Estrous cycle ; Early pregnancy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The number of intraepithelial lymphocytes (IEL) in the luminal and glandular epithelium of the uterus of virgin rats was analysed in diestrus, proestrus and estrus, and in nulliparous rats on days 5, 7 and 9 of pregnancy. IEL number was calculated either with respect to the number of epithelial cells or to the length of epithelium section. It was found that in diestrus, the number of IEL was, on average, 3.7 per 100 luminal epithelial cells or 6.7 per 1 mm of epithelium section, whereas in proestrus, it decreased to 0.9 and 1.2 IEL, respectively. On day 5 of pregnancy (before implantation) the number of IEL decreased further to 0.45 per 100 luminal epithelial cells or 0.9 per 1 mm of epithelium. On days 7 and 9 of pregnancy, IEL number further decreased in implantation sites, whereas in interimplantation sites it remained at the level calculated for day 5 of pregnancy. The population of uterine IEL consisted of small (82–99%) and large (1–18%) lymphocytes. In all stages of the estrous cycle, IEL occurred with a frequency of 68–87% in the basal region, 8–20% in the middle region and 4–12% in the apical region of the luminal epithelium width.
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  • 131
    ISSN: 1432-0878
    Keywords: Retinal pigment epithelium ; Cytoskeleton ; Cytokeratins ; Vimentin ; Desmosomes ; Anura (Rana ridibunda, Xenopus laevis) ; Chicken ; Bovine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In vertebrate tissue development a given cell differentiation pathway is usually associated with a pattern of expression of a specific set of cytoskeletal proteins, including different intermediate filament (IF) and junctional proteins, which is identical in diverse species. The retinal pigment epithelium (RPE) is a layer of polar cells that have very similar morphological features and practically identical functions in different vertebrate species. However, in biochemical and immunolocalization studies of the cytoskeletal proteins of these cells we have noted remarkable interspecies differences. While chicken RPE cells contain only IFs of the vimentin type and do not possess desmosomes and desmosomal proteins RPE cells of diverse amphibian (Rana ridibunda, Xenopus laevis) and mammalian (rat, guinea pig, rabbit, cow, human) species express cytokeratins 8 and 18 either as their sole IF proteins, or together with vimentin IFs as in guinea pig and a certain subpopulation of bovine RPE cells. Plakoglobin, a plaque protein common to desmosomes and the zonula adhaerens exists in RPE cells of all species, whereas desmoplakin and desmoglein have been identified only in RPE desmosomes of frogs and cows, including bovine RPE cell cultures in which cytokeratins have disappeared and vimentin IFs are the only IFs present. These challenging findings show that neither cytokeratin IFs nor desmosomes are necessary for the establishment and function of a polar epithelial cell layer and that the same basic cellular architecture can be achieved by different programs of expression of cytoskeletal proteins. The differences in the composition of the RPE cytoskeleton further indicate that, at least in this tissue, a specific program of expression of IF and desmosomal proteins is not related to the functions of the RPE cell, which are very similar in the various species.
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  • 132
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    Cell & tissue research 254 (1988), S. 251-253 
    ISSN: 1432-0878
    Keywords: Space flight ; Skeletal muscle ; Collagen ; Protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Biochemical determinations of non-collagenous protein and hydroxyproline were made on rat skeletal muscles following 7 days of space flight aboard the NASA space shuttle mission SL-3. Relative to ground-based controls, the wet weight of each experimental muscle was significantly reduced. This was concomitant with a reduction in noncollagenous protein in the muscles. Protein concentration, however, was reduced only in slow-twitch muscles. The effect of space flight on the concentration and hydroxyproline content was different among the muscles. As a result, the loss of muscle mass in some muscles was the consequence of a reduction in both collagenous and non-collagenous proteins, while in others it was primarily the result of a non-collagenous protein loss.
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  • 133
    ISSN: 1432-0878
    Keywords: Pineal complex ; Pinealocytes, receptor line ; Subcommissural organ ; Immunocytochemistry ; Protein secretion ; Neuroendocrine system Geotria australis (Cyclostomata) ; Onkorhynchus kisutch (Teleostei) ; Eupsophus roseus (Anura) ; Heloderma suspectum, Varanus monitor (Lacertilia) ; Domestic fowl ; Rat ; Bovine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary By means of light-microscopic immunocyto-chemistry two polyclonal antibodies (AFRU, ASO; see p. 470) directed against secretory glycoproteins of the subcom-missural organ were shown to cross-react with cells in the pineal organ of lamprey larvae, coho salmon, a toad, two species of lizards, domestic fowl, albino rat and bovine (taxonomic details, see below). The AFRU-immunoreactive cells were identified as pinealocytes of the receptor line (pineal photoreceptors, modified photoreceptors or classical pinealocytes, respectively) either due to their characteristic structural features or by combining AFRU-immunoreaction with S-antigen and opsin immunocytochemistry in the same or adjacent sections. Depending on the species, AFRU- or ASO-immunoreactions were found in the entire perikaryon, inner segments, perinuclear area, and in basal processes facing capillaries or the basal lamina. In most cases, only certain populations of pinealocytes were immunolabeled; these cells were arranged in a peculiar topographical pattern. In lamprey larvae, immunoreactive pinealocytes were observed only in the pineal organ, but not in the parapineal organ. In coho salmon, the immunoreaction occurred in S-antigen-positive pinealocytes of the pineal end-vesicle, but was absent from S-antigen-immunoreactive pinealocytes of the stalk region. In the rat, AFRU-immunoreaction was restricted to S-antigen-immunoreactive pinealocytes found in the deep portion of the pineal organ and the habenular region. These findings support the concept that several types of pinealocytes exist, which differ in their molecular, biochemical and functional features. They also indicate the possibility that the AFRU- and ASO-immunoreactive material found in certain pinealocytes might represent a proteinaceous or peptidic compound, which is synthesized and released from a specialized type of pinealocyte in a hormone-like fashion. This cell type may share functional characteristics with peptidergic neurons or paraneurons.
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  • 134
    ISSN: 1432-0878
    Keywords: Perivascular space ; Cerebrospinal fluid compartments ; Dura mater ; Pacchionian granulations ; Rat ; Cebus apella, Callitrix jacchus (Primates)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary At the sites where a vein penetrates through the dura mater, two aspects deserve particular attention: (i) The delineation of the perivascular cleft, a space belonging to the interstitial cerebrospinal fluid (CSF) compartment, toward the interior hemal milieu of the dura mater. (ii) The relationship between the perivascular arachnoid layer and the subdural neurothelium at the point of vascular penetration. These problems were investigated in the rat and in two species of New-World monkeys (Cebus apella, Callitrix jacchus). Concerning the first aspect, tight appositions of meningeal cells to the vessel wall, the basal lamina of which is widened and enriched with microfibrils, prevent communication between the interstitial CSF in the perivascular cleft and the hemal milieu in the dura mater. With reference to the second aspect, the perivascular arachnoid cells are transformed into neurothelial cells at the point where they become exposed to the hemal milieu of the dura mater and subsequently continuous with the subdural neurothelium. Leptomeningeal protrusions encompassing outer CSF space can penetrate into the dura mater. These protrusions may expand and branch repeatedly, forming along the wall of the durai sinus Pacchionian granulations. At these sites, however, the structural integrity of the sinus wall and the Pacchionian granulation is not lost. Numerous vesiculations not only in the sinus and vascular walls, but also in the cellular arrays of the Pacchionian granulations or paravascular leptomeningeal protrusions indicate mechanisms of transcellular fluid transport. Moreover, the texture of the leptomeningeal protrusions favors an additional function of these structures as a “volume” buffer.
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  • 135
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    Cell & tissue research 251 (1988), S. 171-181 
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Basal lamina ; Laminin ; Anterior pituitary gland ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To determine whether circulating antibodies against laminin can bind in vivo to basement membranes within endocrine glands, affinity-purified sheep or rabbit anti-laminin IgG was intravenously injected into rats. One to five hours after injection, anti-laminin IgG was bound to all basement membranes of adrenal and anterior pituitary glands of mature as well as 2-day-old newborn rats as shown by immunofluorescence microscopy. After the injection of anti-laminin conjugated directly to horseradish peroxidase (HRP), HRP reaction product was also present throughout adrenal and pituitary basement membranes in mature and immature glands 1–5 h post-injection. Ultrathin Lowicryl sections from rats that received unconjugated rabbit anti-laminin IgG 1 h prior to fixation with paraformaldehyde were labeled directly with anti-rabbit IgG-colloidal gold. In these cases, gold also bound specifically over the lamina densa and lamina rara. When adrenal or pituitary glands from mature rats were examined by immunofluorescence 1 week after the injection of sheep anti-laminin IgG, the patterns and amounts of bound sheep IgG were indistinguishable from those observed 1 h after injection. In contrast, significantly less fluorescence was present in glands from 7-day-old rat pups that had received anti-laminin IgG 5 days earlier. In addition, when anti-laminin IgG-HRP was injected into newborns and glands were fixed 5 days later, lengths of labeled endothelial and epithelial basement membranes were often interspersed with unlabeled lengths in zones of cellular proliferation in the outer adrenal cortex and throughout the pituitary gland. These results indicated that unlabeled basement membranes in these regions were probably assembled after the injection of anti-laminin IgG, which would also explain diminished labeling of basement membranes in these animals. Despite the continued presence of heterologous anti-laminin IgG within endocrine basement membranes, however, rat IgG, rat C3, inflammatory cells, or histologic abnormalities were observed in neither newborn nor adult glands under the conditions examined here. Sections from rats injected with control IgG or control IgG-HRP were entirely negative by immunofluorescence, immunoperoxidase, and immunogold techniques. We therefore conclude that (1) apparently large amounts of circulating anti-laminin IgG can bind to adrenal and pituitary basement membranes, and (2) at least some of these basement membranes are assembled during development by progressive splicing of newly synthesized matrix into that already present.
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  • 136
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    Cell & tissue research 252 (1988), S. 181-190 
    ISSN: 1432-0878
    Keywords: Embryonic rat brain ; Cell culture ; Development ; NILE-glycoprotein ; Neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Fetal rat cerebral cells underwent neuronal differentiation in culture. This process was accompanied by distinct changes in the cellular glycoprotein pattern. The incorporation of [3H]-fucose into two proteins of apparent molecular weights of 30000 and 60000 daltons was significantly decreased and specific developmental changes were observed in a group of glycoproteins with high molecular weights (150000–250000 dalton). By means of indirect immunoprecipitation one of them was identified as NILE gp (nerve growth factor-inducible large external) glycoprotein (200000 dalton), a marker of central and peripheral neurons. Its developmental expression on neurons of dissociated rat cerebral cultures was studied using the indirect immunofluorescence technique and compared to the fluorescent-labeling pattern of other neuronal markers. Neurons expressing NILE gp were detected as early as after one day in culture. No preferential staining of neuntes versus cell bodies was observed. Two classes of NILE gp-positive cells were identified. One group consisted of a rounded cell-type, whereas the other group was represented by larger, more spindle-shaped neurons with a limited number of neuritic processes. In most cases one of these neuritic processes was preferentially labeled. Astroglia cells, as identified by immunolabeling with antisera against the glial acidic fibrillary protein, were observed to develop and mature after the first week in culture. NILE-positive neurons were found to be positioned in close association with glial cell processes.
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  • 137
    ISSN: 1432-0878
    Keywords: Endocytosis ; Absorptive cells ; Ileum ; Intestine, small ; Apical tubules ; Membrane recycling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ileal absorptive cells of suckling rats exhibit high levels of endocytic activity being engaged in nonselective uptake of macromolecules from the intestinal lumen. The apical cytoplasm usually contains an extensive network of small, membrane-limited tubules (apical tubules: AT), in addition to newly formed endocytic vesicles and large endocytic vacuoles. To determine whether the AT are directly involved in the endocytic process by carrying the tracer into the cell, we have analysed movements of the apical cell membrane of the ileal absorptive cells by using a membrane-bound tracer (horseradish peroxidase-labelled cancanavalin-A: Con-A HRP). The ileal absorptive cells were exposed in vitro to Con-A HRP for 10 min at 4° C, incubated for different times in Con-A free medium at 37° C, and prepared for electron microscopy. After 1 min incubation at 37° C, invaginations of the apical cell membrane, including coated pits, and endocytic vesicles were labelled with HRP-reaction product, whereas the AT and large endocytic vacuoles were negative. After 2.5 min, almost all the large endocytic vacuoles were labelled with reaction product, which was seen in their vacuolar lumen and along the luminal surface of their limiting membrane. A few AT with reaction product were seen in the apical cytoplasm; they were in frequent connection with the reaction-positive large endocytic vacuoles. With increasing incubation time, the number of the labelled AT increased. Thus, after 15 min at 37° C, the apical cytoplasm was fully occupied by the reaction-positive AT. The ends of these AT were often continuous with small spherical coated vesicles. No reaction product was detected in the Golgi complex at any time after incubation. These observations indicate that the AT located in the apical cytoplasm probably originate by budding off from the large endocytic vacuoles, rather than being involved in the process of endocytosis.
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  • 138
    ISSN: 1432-0878
    Keywords: Periodontal ligament ; Incisor ; Neurofilament protein ; S-100 protein ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Nervous elements in the periodontal ligament and dental pulp of rat incisors were investigated by means of immunohistochemistry for neurofilament protein (NFP) and glia-specific S-100 protein. The periodontal ligament in the incisors was densely innervated by NFP-immunoreactive nerve fibers; the distribution of the nerve fibers and their terminations differed markedly from those in molars. NFP-positive, thick nerve bundles entered the lingual periodontal ligament through slits located in the mid-region of the alveolar socket, and immediately formed numerous Ruffini-like corpuscles. In the labial periodontal ligament, all of the NFP-immunoreactive nerve fibers terminated in free endings. The restricted location of the stretch receptor, Ruffini-like corpuscle, in the lingual periodontal ligament appears to be an essential element, because this region is regularly extended during mastication. The nervous elements were restricted to the alveolar half of the periodontal ligament in every region; they avoided the dental half of the periodontal ligament, which presumably moves continuously with the tooth. Pulpal nerve fibers in incisors also showed a characteristic distribution different from those in molars; individual nerve fibers with beaded structures ran in the center of the pulp toward the incisai edge, and did not form the subodontoblastic nerve plexus of Raschkow. Immunostaining for S-100 protein revealed a distribution pattern of nervous elements similar to that for NFP, suggesting that the nerves supplying the periodontal ligament and dental pulp were mostly covered by a Schwann sheath.
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  • 139
    ISSN: 1432-0878
    Keywords: Posterior pituitary ; Immunocytochemistry ; Anti-GABA ; GABA-transaminase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An antibody against gamma-aminobutyric acid (GABA) was used to identify GABAergic elements immunocytochemically in the rat posterior pituitary. In order to increase the intracellular concentration of GABA, rats were treated with the GABA-transaminase inhibitor gamma-vinyl-GABA (GVG). Light-microscopic observations of Vibratome and semithin sections revealed the presence of numerous immunoreactive nerve fibers throughout the neural lobe; the mean number and length of these fibers increased by 90% after GVG treatment. Electron microscopy demonstrated the immunostained axons to be of small diameter. The reaction product was confined to small vesicles. No immunostaining occurred in pituicytes. The richness of the GABAergic innervation of the neural lobe contrasts with previous reports using antibodies against glutamate decarboxylase and supports the idea that GABA participates in the presynaptic control of neurosecretion.
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  • 140
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    Cell & tissue research 251 (1988), S. 65-70 
    ISSN: 1432-0878
    Keywords: Adipose tissue ; Cell proliferation ; Cell differentiation ; Histochemistry ; Swine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cells in fetal adipose tissue and cells in vitro are characterized by rapid proliferation. Serum factors have been shown to be important for the rapid proliferation of cells in vitro. The present experiment was performed to determine if neuroendocrine regulatory mechanisms of the fetus can influence the actions of serum factors on preadipocyte proliferation and differentiation in vitro. Sera were obtained from decapitated fetal pigs and intact littermates during gestation. Sera were tested for their effects on primary cultures of preadipocytes and stromalvascular cells derived from inguinal adipose tissue of young Sprague-Dawley rats. Coverslip cultures were used for histochemical analysis of enzymes after 12 days of incubation with test media. Analysis of growth curves produced from sequential [3H]-thymidine labeling indicated that fetal age influences rates of proliferation. Sera from decapitated fetal pigs specifically reduced the number of proliferating preadipocytes in culture. Sera from decapitated fetal pigs induced a minimum of 50% less differentiation of sn-glycerol-3-phosphate dehydrogenase activity than sera from intact pigs at all fetal ages. Histochemical staining for enzymes of differentiating preadipocytes was also reduced in cultures incubated with sera from decapitated fetal pigs in comparison to sera from intact pigs. The present study has demonstrated that the in vivo effect of decapitation on fetal adipose tissue development is a consequence of alterations in systemic factors present in serum in response to removal of central regulation by the hypothalamic-pituitary axis.
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  • 141
    ISSN: 1432-0878
    Keywords: Monoclonal antibody ; Blood-brain barrier ; Cerebral pericytes ; Transporting epithelia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A monoclonal antibody that recognizes a 140 kDa peripheral plasma membrane protein in pericytes of nervous tissues of the rat is described. Microvessels of brain cortex and perineurium of peripheral nerves are shown to react positively to this antibody. The antigen is absent in brain regions that lack a blood-brain barrier, i.e., choroid plexuses and area postrema. Antigen expression starts as early as day 18 of embryonic development. By means of immuno-electron microscopy the 140 kDa antigen was detected as clusters along the entire circumference of cerebral pericytes. The same antigenic determinant is also expressed in apical domains of plasma membranes of a variety of transporting epithelia, such as hepatocytes, enterocytes of the small intestine, and epithelial cells of proximal tubules of the kidney. We postulate the 140 kDa protein as being a constituent of the pericytes involved in regulative functions of the blood-brain barrier.
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  • 142
    ISSN: 1432-0878
    Keywords: Ciliary epithelium ; Orthogonal arrays of particles ; Filipin ; Freeze-fracture ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary It has been suggested that orthogonal arrays of particles may increase the rigidity of plasma membrane, as does cholesterol. Therefore, using freeze-fractured non- pigmented ciliary epithelium, the distribution of such arrays was compared to the distribution of membrane deformations induced by the sterol-probes filipin and digitonin in different domains of the basolateral plasma membrane. The distribution of orthogonal arrays of particles was homogeneous between different regions of the basolateral membrane of the non-pigmented ciliary epithelium, while the number of filipin-induced alterations was nearly 4 times higher in the membrane domains not in contact with the basal lamina than in domains in contact with it. Contrary to the homogeneous distribution of arrays, digitonin-induced deformations also differed markedly in these two basolateral membrane domains. Considering that a marked positive response to sterol probes implies a high sterol content, we conclude that orthogonal arrays of particles can occur in plasma membrane regions well-provided with cholesterol and not in direct contact with the basal lamina. Other possible roles of these arrays are discussed.
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  • 143
    ISSN: 1432-0878
    Keywords: Bone phosphoprotein ; Osteopontin ; Kidney ; Inner ear ; Trigeminal nerve ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous immunohistochemical data have shown that the 44-kDal bone phosphoprotein (44K BPP, also called sialoprotein I or oestopontin) recently isolated in our laboratory was synthesized by osteoblasts and osteocytes and was expressed early during differentiation of boneforming cells. We report here the presence of 44K BPP antigenicity at certain ectopic sites, namely, the proximal-convoluted tubule of the kidney, neurons, sensory and secretory cells in the internal ear. To insure specificity and reproducibility, different immunohistochemical methods were used and affinity-purified antibodies against two separate preparations of pure 44K BPP were tested. In the cells of the proximal-convoluted tubule, 44K BPP immunoreactivity was observed within apical endocytotic vacuoles and within lysosomes. This staining thus correlates with the degradation of the 44K BPP epitope which we previously demonstrated to occur in serum. On the other hand, in the neurons of the acoustic ganglion and the sensory cells of the macula, 44K BPP immunoreactivity was associated with the Golgi apparatus indicating synthesis and secretion by these cells. The finding that the 44K BPP (or a structurally related molecule) is synthesized by neurons and neuroepithelial cells deserves further investigation with respect to a possible embryologie relationship between neuroectodermal cells and the precursors of some bone forming-cells of the skull.
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  • 144
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    Cell & tissue research 251 (1988), S. 117-121 
    ISSN: 1432-0878
    Keywords: Collagen ; Submucosa ; Intestine ; Scanning electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The three-dimensional architecture of the submucosal collagen fibres of the rat (3 weeks old) small intestine was examined by scanning electron microscopy using a selective microdissection method. The main framework of the submucosa was composed of two arrays of collagen fibre bundles running diagonally around the intestinal wall, one set in a clockwise direction, the other counterclockwise. These fibre bundles were about 5 μm in diameter and were oriented at a range of angle ± 30°–50° to the longitudinal axis of the intestine. With the advantage of the SEM observation it was demonstrated that these fibres in different arrays did not constitute two separate layers but interwove to form a unified lattice sheet. An irregular network of fine collagen fibrils over the main framework was also seen. The significance of their arrangement is discussed with respect to the skeletal function of the submucosa in the intestine.
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  • 145
    ISSN: 1432-0878
    Keywords: Adipocyte ; Primary culture ; Collagen ; Fibronectin ; Serum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of collagenous substrata, fibronectin, and fetal bovine serum on the adhesion, proliferation, and adipogenesis of rat stromal-vascular cells are reported. There was no effect on initial stromal-vascular cell-attachment by fetal bovine serum or fibronectin. The number of cells attached to a hydrated collagen-gel was almost twice (P〈0.04) the number attached to dried collagen-gel or dried denatured collagen-gel. Total number of cells after 5 days in culture was similar among the collagenous substrata and among the treatments with or without fibronectin in the growth media. Total number of cells increased significantly (P〈0.02) with 10% FBS. Adipocytic formation was inhibited by hydrated collagen-gel (P〈0.02) compared to dried collagen-gel or dried, denatured collagenous substrata. An interaction occurred between dried, denatured gel and fetal bovine serum so that total formation of adipocytes increased by increasing the level of fetal bovine serum (P〈0.07). Adipocytic formation was inhibited by hydrated collagen-gel at all levels of fetal bovine serum. The percentage of cells that converted to adipocytes was significantly lower (P〈0.01) on hydrated collagen-gel compared to dried, denatured or dried collagen-gel. Percentage of conversion was not significantly different among levels of fetal bovine serum, although this percentage increased as fetal bovine serum level increased. Adipocytic conversion was not different between fibronectin-treated or untreated cells. Morphology of stromal vascular cells was similar on dried collagen and dried, denatured collagen-gel, but tended to remain bipolar on hydrated collagen-gel. These studies indicate that fetal bovine serum in combination with the extracellular matrix (dried, denatured collagen) increased the differentiation of rat stromal-vascular cells into adipocytes, and that hydrated collagen inhibited differentiation.
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  • 146
    ISSN: 1432-0878
    Keywords: Atrial natriuretic peptide ; Ventricular myocytes ; Atrial myocytes ; Cell culture ; Secretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We have demonstrated that atrial natriuretic peptide-like immunoreactivity is stored and secreted by ventricular and atrial myocytes in dissociated cell culture preparations from the heart of newborn rat. Culture preparations were maintained in either foetal calf serum-supplemented medium 199 or in hormone-supplemented, serum-free medium 199. The presence of atrial natriuretic peptidelike immunoreactivity in the cultured myocytes was demonstrated at both light-and electron-microscopical levels. Release of atrial natriuretic peptide-like immunoreactivity into the culture medium was measured by radioimmunoassay; molecular forms of the stored and secreted peptide were determined by gel column chromatography. The atrial natriuretic peptide-like immunoreactivity of cultured atrial and ventricular myocytes was concentrated in the perinuclear cytoplasm and was localised to electron-dense secretory granules. The number of immunoreactive ventricular myocytes and the intensity of their immunofluorescence changed with time in culture and was higher in cultures in foetal calf serum-supplemented medium than in serum-free medium. Gamma-atrial natriuretic peptide was stored and released by cultured atrial and ventricular myocytes, but was broken down to alpha-atrial natriuretic peptide in the growth medium. This process was foetal calf serum-independent, since it occurred in both the media used, indicating that cardiac myocytes in culture may release a factor that cleaves gamma-atrial natriuretic peptide to form alphaatrial natriuretic peptide.
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  • 147
    ISSN: 1432-0878
    Keywords: Enkephalin-nerves ; Transient appearance ; Submandibular gland ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A time course study with enkephalin(Enk)-like immunoreactivity has revealed that nerve fibers intensely immunoreactive for Enk-8 appeared transiently only during the postnatal week 2 and 4 within the acini as well as in the inter- and intralobular connective tissues of the submandibular gland of rats. At these stages numerous nerve fibers immunoreactive for tyrosine hydroxylase (TH) appeared also in the inter- and intralobular connective tissues and within the acini. Coincidently with these postnatal stages, abundant Enk-immunoreactive principal ganglion cells appeared in the superior cervical ganglion. These were not immunoreactive for neuropeptide tyrosine (NPY). A substantial number of Enk-immunoreactive ganglion cells were also present in the submandibular ganglia at these younger postnatal stages. Superior cervical ganglionectomy at these stages resulted in a marked decrease in number of the inter- and intralobular Enk-immunoreactive nerve fibers, a slight decrease in number of the intraacinar Enk-immunoreactive nerve fibers, and almost complete disappearance of intraglandular TH-immunoreactive nerve fibers. Immuno-electron-microscopic analysis revealed that Enk-immunoreactive nerve fibers in the submandibular gland were identified as electron-dense neuronal profiles enclosed by Schwann cells in the inter- and intralobular connective tissues and those directly apposed to secretory cells within the acini. They contained small clear vesicles mixed with some large granular vesicles. After postnatal week 6, no Enk-immunoreactive nerve fibers were detected in the submandibular gland, and no TH-immunoreactive nerve fibers were seen within the acini, while TH-immunoreactive nerve fibers remained numerous in the inter- and intralobular connective tissues. These findings indicate that both sympathetic and parasympathetic nerve fibers exhibit Enk-like immunoreactivity transiently during postnatal weeks 2 and 4. It is further indicated that the inter- and intralobular nerve fibers lose Enk-like immunoreactivity while the intraacinar fibers disappear at the adult stage.
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  • 148
    ISSN: 1432-0878
    Keywords: Gap junctions ; cAMP ; Theophylline ; Freeze-fracture ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In view of the presumed involvement of gap junctions in the coordination of metabolic activities, the influence of cAMP as a regulatory signal of cell metabolism on gap junctions of hepatocytes has been examined. Male rats received two intraperitoneal doses of 10 mg dibutyryl cAMP/100 g body weight with a time interval of 2.5 h and were decapitated 2.5 h later. After this 5-h interval, analysis of freeze-fracture replicas of fixed liver tissue revealed an increase in the mean (± SEM) gap-junctional membrane portion on the lateral hepatocyte membranes from 0.049 + 0.003 (n = 66) in controls to 0.061 ± 0.003 (n = 70) in treated rats, while the configuration of the connexons appeared unaltered. This effect could not be reinforced by prior administration of aminophylline: the relative gapjunctional area is similarly extended from 0.054 ± 0.003 (n = 126) in the control group to 0.065 ± 0.004 (n = 105) in the experimental animals. Probing for the time course of the junctional response, a group of rats was sacrificed 3 h after the onset of treatment. Already within this time, the gapjunctional area is augmented from 0.042 ± 0.004 (n = 63) in the concurrent controls to 0.069 ± 0.006 (n = 42) in the treated rats. These statistically significant increases in area may suggest a stimulating effect of cAMP on gap junctions of hepatocytes in vivo.
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  • 149
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    Cell & tissue research 251 (1988), S. 523-529 
    ISSN: 1432-0878
    Keywords: Glial fibrillary acidic (GFA) protein ; S-100 protein ; Supportive cells ; Intestine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The non-neuronal, supportive cells of the enteric nerve plexus were investigated in the colon and rectum of adult and developing rats by means of immunohistochemistry, utilizing antisera against GFA protein and S-100 protein. Immunoreactivity to GFA protein was almost exclusively found in cells associated with the myenteric plexus and a small number of cells within the submucous ganglia. On the other hand, the use of S-100 protein antiserum resulted in the visualization of all supportive elements in the enteric nervous system. However, two types of supportive cells could be tentatively differentiated in the enteric nerve plexus during the second week of postnatal development, using GFA protein and S-100 protein antisera; GFA protein-positive cells were clearly discernible from S-100 protein-positive cells in terms of both the morphological profiles and immunohistochemical properties. It was assumed that at least two different types of supportive cells are contained in the enteric nerve plexus. We suggest that in the enteric nervous system the terms “glial cells” and “Schwann cells” should be employed to designate the supportive cells containing GFA and S-100 proteins, and cells containing S-100 protein, respectively. We discuss the possibility that glial cells are associated with the parasympathetic preganglionic fibres directly derived from the central nervous system, while Schwann cells originate from the neural crest.
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  • 150
    ISSN: 1432-0878
    Keywords: Calcium-binding protein ; Enteric nervous system ; Intestine ; Immunocytochemistry ; Guinea-pig ; Rat ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunoreactivity for vitamin D-dependent calcium-binding protein (CaBP) has been localized in nerve cell bodies and nerve fibres in the gastrointestinal tracts of guinea-pig, rat and man. CaBP immunoreactivity was found in a high proportion of nerve cell bodies of the myenteric plexus, particularly in the small intestine. It was also found in submucous neurons of the small and large intestines. Immunoreactive nerve fibres were numerous in the myenteric ganglia, and were also common in the submucous ganglia and in the intestinal mucosa. Immunoreactive fibres were rare in the circular and longitudinal muscle coats. In the myenteric ganglia of the guinea-pig small intestine the immunoreactivity is restricted to one class of nerve cell bodies, type-II neurons of Dogiel, which display calcium action potentials in their cell bodies. These neurons were also immunoreactive with antibodies to spot 35 protein, a calcium-binding protein from the cerebellum. From the distribution of their terminals and the electrophysiological properties of these neurons it is suggested they might be sensory neurons, or perhaps interneurons. The discovery of CaBP in restricted sub-groups of enteric neurons may provide an important key for the analysis of their functions.
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  • 151
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    Cell & tissue research 251 (1988), S. 275-280 
    ISSN: 1432-0878
    Keywords: Cerebral arteries ; Vasoactive intestinal polypeptide ; Vascular innervation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The pathway of nerves with vasoactive intestinal polypeptide(VIP)-like immunoreactivity to the major cerebral arteries was studied in rats by means of the indirect immunofluorescent method. The fibers are densely distributed in the ethmoidal nerves and in the adventitia of both the external and internal ethmoidal arteries. Section of both ethmoidal nerves and external ethmoidal arteries before they enter the cranial cavity induced a marked reduction of VIP-like immunoreactive fibers in the walls of the vessels of the circle of Willis and its major branches. However, section of the external ethmoidal artery alone did not result in visible changes of the nerves around major cerebral arteries. The present study suggests that VIP-like immunoreactive fibers surrounding major cerebral arteries of the rat arise from fibers in the ethmoidal nerve showing immunoreactivity to VIP.
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  • 152
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    Cell & tissue research 251 (1988), S. 243-248 
    ISSN: 1432-0878
    Keywords: Thoracic duct ; Smooth muscle cell ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The three-dimensional cytoarchitecture and ultrastructure of the smooth muscle cells in the wall of the rat thoracic duct were investigated by scanning and transmission electron microscopy. The muscle layer basically consists of a single layer of circularly arranged cells. The smooth muscle cell is fusiform or ribbon-like in shape, as in veins or venules with a similar or smaller diameter. Connections by spinous processes are observed between adjacent muscle cells along their length. Spot-like membrane contacts frequently occur in areas where facing membranes are closely apposed. These are thought to be gap junctions and may be responsible for electrical coupling and mechanical attachment. Large invaginations arranged regularly in rows on the surface of the smooth muscle cells can be observed. These invaginations are closely associated with a flattened sarcoplasmic reticulum, and caveolae tend to open into the invaginations.
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  • 153
    ISSN: 1432-0878
    Keywords: GABA ; Glutamate decarboxylase ; GABA transaminase ; Exocrine pancreas ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural immunohistochemical localization of gamma aminobutyric acid (GABA) and its regulating enzymes, l-glutamate decarboxylase (GAD) and gamma aminobutyrate-α-ketoglutarate transaminase, was determined utilizing an immunogold post-embedding protocol in pancreatic exocrine tissue. Within the acinar cell, GABA and its biosynthetic enzyme, GAD, were localized in zymogen granules. Quantitative analysis of the GABA immunoreactivity in the acinar cell revealed 1.7±0.5 gold particles/μm2 over the cytoplasm, 36.6±14.1 gold particles/ μm2 over the zymogen granules, and 2.9±2.1 gold particles /μm2 over the mitochondria. Quantitative analysis of the distribution of colloidal gold particles, representing glutamate decarboxylase immunoreactivity in the acinar cells, revealed 38.4±2.5 gold particles/μm2 over the zymogen granules, 4.7±1.1 gold particles/μm2 over the mitochondria and 6.3±0.5 gold particles/μm2 over the remainder of the cytoplasm. Substitution of normal sheep serum for the sheep anti-glutamate decarboxylase serum revealed a significant (p〈 0.001) decrease of the colloidal gold particle distribution over the zymogen granules and cytoplasmic compartments of the acini. Gamma aminobutyrate -α-ketoglutarate transaminase, the catabolic enzyme for GABA, was not detected in the mitochondria, zymogen granules, and cytoplasm of the acinar cell, suggesting that GABA is not catabolized within the acinar cell. Preabsorption and substitution controls resulted in an absence of labeling. These results suggest that GABA may act extracellularly and/or have a role within the zymogen granule in the exocrine pancreas.
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  • 154
    ISSN: 1432-0878
    Keywords: MPTP ; Rat ; Nigrostriatum ; Parkinsonism ; Immunocytochemistry ; Tyrosine hydroxylase ; Animal model ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Several laboratories have reported that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine causes damage to the nigral dopamine neurons of man, monkey, and mouse. Controversial data suggest that a rat model of Parkinsonism may be possible. Although loss of dopamine cells has not been detected in the rat brain, our immunocytochemical studies show that immunoreactive tyrosine hydroxylase, the rate-limiting enzyme which synthesizes dopamine, is significantly reduced in concentration, or its antigenicity altered, in substantia nigra/pars compacta as well as the caudate nucleus. Optical density measurements demonstrate the reduction or alteration of immunoreactive tyrosine hydroxylase in nigro-striatal neurons, indicating that axonal terminals, as well as parent perikarya, may be sensitive to the drug. After treatment, abnormal morphological remodelling may result in the affected neuronal processes, perhaps indicating sublethal toxicity, followed by slow recovery. Despite the lack of nigral cell death, it is proposed that the present data support the use of the rat as a model to investigate the early effects of Parkinsonism induced by this agent, and the biological mechanisms of cellular recovery.
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  • 155
    ISSN: 1432-0878
    Keywords: Pancreas, endocrine ; Stomach ; Intestine ; Immunohistochemistry ; Thyrotropin-releasing hormone (TRH) ; Somatostatin ; Avian pancreatic polypeptide ; Insulin ; Gastrin ; Rat ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary By use of the indirect immunofluorescence technique, the cellular localization of thyrotropin-releasing hormone (TRH) was studied in the gastrointestinal tract of rats and guinea pigs of different ages. TRH-like immunoreactivity (LI) was observed in many pancreatic islet cells of young rats and guinea pigs but only in single cells of 6-month-old rats. In aged guinea pigs, a reduction in the number of TRH-positive cells was evident; however, numerous strongly fluorescent cells were still present. In the guinea pig, TRH-LI was in addition observed in gastrin cells in the stomach. TRH-positive nerve fibers occurred in the myenteric plexus of the oesophagus, stomach and intestine of the rat, and in the muscle layers of the guinea pig. These results suggest a functional role of TRH both as hormone and neuroactive compound in various portions and sites of the gastro-intestinal tract of the rat and guinea pig
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  • 156
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    Cell & tissue research 251 (1988), S. 205-214 
    ISSN: 1432-0878
    Keywords: Kupffer cells ; Granulocytes ; Ultrastructure ; Lipopolysaccharide ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of Kupffer cells has been studied at various times after an intravenous injection of lipopolysaccharide of Salmonella abortus equii. The most prominent effects were: an increase in the number and dimensions of phagocytic vacuoles (often containing ingested LPS and neutrophilic granulocytes); mitochondrial damage, including disintegration of the matrix and cristae; an increase in the amount of dilated, lucent rough endoplasmic reticulum; presence of fat droplets in the cytoplasm. Five days after injection of lipopolysaccharide, the Kupffer cells had resumed their normal ultrastructure. Several minutes after injection of lipopolysaccharide, platelets adhered to the Kupffer and endothelial cells. Between one and six hours, neutrophilic granulocytes accumulated in the liver sinusoids. The resulting obstruction of the hepatic microcirculation most probably affected cellular ultrastructure by ischaemia. At three days, the number of Kupffer cells was doubled, and increased further at later time intervals.
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  • 157
    ISSN: 1432-0878
    Keywords: Neuropeptide ; Intracellular localization ; Sympathetic ganglia ; Colchicine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In colchicine-pretreated cells of sympathetic ganglia, intensely NPY-immunoreactive material was localized within vacuoles and vesicles of the disorganized, widely dispersed Golgi apparatus. Intensely positive large granular vesicles, which are known to be one of major storage sites of various peptides in the autonomic nerve endings, were essentially unobserved in the perikaryal cytoplasm. The present finding provides evidence that one pool of NPY-like immunoreactivity is localized in the Golgi apparatus of colchicine-pretreated as well as normal sympathetic ganglion cells. It is also clear that visualization of NPY-immunoreactive somata by colchicine-pretreatment in the sympathetic ganglia is due to the accumulation of the neuropeptide in the disorganized Golgi stacks instead of increased amount of the large granular vesicles containing NPY.
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  • 158
    ISSN: 1432-0878
    Keywords: Receptor-mediated endocytosis ; Chondroitin sulphate ; Colloidal gold ; Liver endothelial cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Endocytosis via the hyaluronic acid/chondroitin sulphate receptor of rat liver endothelial cells was studied ultrastructurally, by use of a probe consisting of chondroitin sulphate proteoglycan attached to 15-nm gold particles. The probe bound to the surface of the cells exclusively in coated regions of the plasma membrane. Internalization at 37° C took place in less than one minute during which time interval the bound probe was transferred to coated vesicles. Further transfer to lysosomes was delayed in association with an accumulation of probes in a prelysosomal compartment consisting of large vacuoles in which probes lined the inner aspect of the membrane. Transport to lysosomes occurred only after a lag phase of at least 40–60 min at 37° C.
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  • 159
    ISSN: 1619-7089
    Keywords: MIBG ; Monoamine uptake ; Blood platelets ; Rat ; 6OH-DA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The uptake of MIBG, a scintigraphic agent widely used in the detection of APUD tumors, was studied with a pharmacological approach on an in vitro and an in vivo models. MIBG as well as norepinephrine (NE) was taken up by human blood platelets, a model for presynaptic nerve endings amine uptake, with a thermodependant mechanism. MIBG and NE uptake was inhibited by desimipramine and reserpine. However, MIBG but not NE uptake was inhibited by fluvoxamine, a serotonin (5HT) uptake inhibitor. This suggests that MIBG is a NE and also a 5HT uptake tracer which involves uptake one and vesicular storage mechanisms. In rats treated with 6-hydroxydopamine to induced a chemical sympathectomy, we observed an inhibition of uptake similar for MIBG and NE in the heart, the salivary glands and the spleen, but no effect was observed in the liver. Some clinical inferences to best investigate specific monoamine uptake are drawn from these results.
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  • 160
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    Protoplasma 145 (1988), S. 195-199 
    ISSN: 1615-6102
    Keywords: Microtubule-associated proteins ; Development ; Rat ; Quail ; Xenopus laevis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In the adult rat brain, MAP 2 is a high-molecular weight protein that is highly concentrated in dendrites. Immunoblots of homogenates of developing rat brain have indicated that a low-molecular weight form of MAP 2, MAP 2 c, is transiently expressed as the brain is undergoing morphogenesis. Using MAP 2-specific monoclonal antibodies, we have demonstrated that the compartmentalization of high-molecular weight MAP 2 and the developmental regulation of MAP 2 are conserved in mammalian, avian, and amphibian brain. We have also determined the distribution of MAP 2 c in developing neuronal tissue. MAP 2 c appears before high-molecular weight MAP 2 in developing neurons, and in contrast to the dendrite-specific high-molecular weight forms of MAP 2, MAP 2 c is present in axons and glia. We have also shown that MAP 2 c is present in the adult rat retina, where it is concentrated in regenerative photosensitive cells. The transient expression of MAP 2 c in the developing brain of three species as well as in adult photosensitive cells suggests a role for this protein in neurite growth and plasticity.
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  • 161
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    European journal of applied physiology 57 (1988), S. 33-38 
    ISSN: 1439-6327
    Keywords: Interstitial volume ; Potassium concentration ; Heart rate ; Rat ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During exercise heart rate is influenced by reflexogenic drives which are elicited by receptors situated in the interstitial space. Since the structure of interstitial tissue is complex (e.g. fixed negative charges of glycosaminoglycans), the situation in the immediate surrounding of the receptors might differ from the free fluid phases of blood or lymph in which the concentrations of stimulating substances are usually determined. Physiological variations of the interstitial structure may be due to changes in interstitial volume induced by exercise or the hydrostatic effects on body fluids. The objective of the present study was to investigate the effect of the interstitial volume on the relationship between heart rate and K+ stimuli applied through the muscle blood vessels. The calves of 12 male Wistar rats were artificially perfused and separated from the rest of the body with the sciatic nerve remaining intact. In these preparations the heart rate (HR) responses to low (4 mM) and high (8 mM) potassium concentrations were determined at different interstitial volumes. Expansion of the interstitial volume was obtained by reducing the colloid-osmotic pressure of the perfusate. The combination of intracellular oedema and mechanical limitation of total volume expansion (tapeing) was utilized to decrease the interstitial volume. When switching between the low and high potassium concentrations, significant heart rate responses could be observed only with reduced interstitial volume. It is suggested that the interstitial structure surrounding the muscular receptors modifies the relationship between heart rate response and the K+ stimuli determined in blood or lymph.
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  • 162
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    European journal of applied physiology 57 (1988), S. 671-676 
    ISSN: 1439-6327
    Keywords: Rat ; Left ventricle ; Training ; Metoprolol ; Propranolol ; Capillary density ; Myocyte ; Atrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The study was designed to evaluate the effects of eight weeks of exercise training or training-β-adrenergic blockade combination on gross and microscopic alterations of rat cardiac muscle and microvascular bed. Rats were randomly assigned to either sedentary control (C), trained (T), metoprolol-trained (MT), or propranolol-trained (pT) groups. The training protocol involved treadmill running for 8 weeks at 0.5 m s−1, 20% grade. Earlier experiments by us showed this training protocol to be effective in producing significant changes in selected skeletal muscle enzyme activities in all trained groups. In the current study an absolute reduction in left ventricular (LV) weight was observed in the PT compared to the C group (0.91±0.02 vs. 1.04±0.04 g,P〈0.05). LV weight in the T and MT groups was no different from C so that LV to BW ratio (mg·g−1) was significantly increased (P〈0.05) due to a similar reduction in body weight (BW) in all three training groups. Morphometric analysis of LV myocardium revealed no significant differences in myocyte mean cross-sectional area (μm2) in any of the groups (289±16-C, 332±20-T, 281±44-MT, and 273±12-PT). Capillary density independently calculated by light and electron microscopy was unchanged by training or trainings-blockade combination. It was concluded that training of sufficient intensity and duration to produce skeletal muscle enzyme adaptations does not necessarily produce myocyte hypertrophy or alter LV capillarity. Additionally functioningβ-adrenergic receptors appear to play a role in both the central and peripheral adaptations to endurance exercise training.
    Type of Medium: Electronic Resource
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  • 163
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    European journal of applied physiology 58 (1988), S. 120-124 
    ISSN: 1439-6327
    Keywords: Respiratory muscle ; Glycogen ; Exercise ; Fasting ; Nicotinic acid ; Beta-adrenergic receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of prolonged exercise on the glycogen level in the respiratory muscles (diaphragm — D, external intercostal — IE and internal — II) has been studied in four groups of rats: 1-control, 2-fasted for 24 h, 3-treated with nicotinic acid and 4-treated with propranolol. There was a sharp reduction in glycogen level in each muscle after 30 min exercise in the control and fasted groups. Exercise till exhaustion further lowered the glycogen level in D in the control group and in IE and II in the fasted group. In the fasted group, the level of glycogen in each muscle, at rest, and after 30 min exercise, and in IE and II muscles after exercise till exhaustion was lower than in the control group. Nicotinic acid did not affect the glycogen level either at rest or during exercise as compared with the control group. Propranolol increased the glycogen level in the muscles at rest and during 30 min exercise. It partially prevented glycogen mobilization in D and IE and fully in II during exercise till exhaustion. In the control group, 24 and 48 h after exercise till exhaustion, the level of glycogen in each muscle exceeded the resting control value. It is concluded that exercise-induced glycogen metabolism in the respiratory muscles differs in some respects from that in the limb or heart muscles.
    Type of Medium: Electronic Resource
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  • 164
    ISSN: 1573-6903
    Keywords: Rat ; protein deprivation ; brain ; temperature ; amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous reports on early-induced protein-calorie malnutrition (PCM) in rats have indicated alterations in the concentration of free amino acids and of protein synthesis in the brain. Recently it was shown that early-induced protein deprivation (PD) retards the development of thermoregulation. This resulted in a failure to maintain a normal rectal temperature after short exposure to room temperature (+22°C) still at the age of 20–25 days corresponding to changes seen in normal rats at an age of 10–15 days. In the present study, 20-day old PD and normal rats where examined with regard to the effect of exposure to room temperature on brain temperature and on brain free amino acids. The results show a similar reduction in brain and rectal temperature of the PD rats occuring within 30 minutes after exposure to room temperature. The reduction was in the range of 5°C. PD rats kept in room temperature for 5 hours and then allowed to recover at 32.5°C showed a slow increase in brain and rectal temperature but normal temperatures were not reached even after 1 hour. The concentration of free amino acids in the brain was examined in rats kept for 1 hour at room temperature or at 32.5°C. In the PD rats kept at 32.5°C, free aspartate and glutamate were reduced whereas taurine, GABA and glycine were increased as compared to their corresponding control rats. As a result of the reduced brain temperature in PD rats exposed to room temperature there was a reduction in free asparagine. The lability of the pool of asparagine may be related to the low levels of aspartate and glutamate in PD rats. On the basis of the present findings it is recommended that temperature-sensitive parameters are examined in PCM rats at a normal body temperature.
    Type of Medium: Electronic Resource
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  • 165
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    European archives of oto-rhino-laryngology and head & neck 245 (1988), S. 136-141 
    ISSN: 1434-4726
    Keywords: Tympanic membrane structure ; Topical anesthetics ; Emla ; Rat ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A eutectic mixture of two anesthetic solutions is that of lidocaine and prilocaine, which is available commercially as Emla (eutectic mixture of local anesthetics). This solution is commonly used in clinics in superficial skin surgery and when inserting intravenous catheters, and we also wanted to determine its surface effects when applied onto the tympanic membranes (TM) of rats and guinea pigs as animal models. The animals were observed by otomicroscopy for 2 weeks up to 5 months after administrations of the anesthetic solution. Tissue specimens were then obtained for light microscopy and fine structural analysis. The application of Emla caused minor structural changes to the rat TM, but hardly any alterations to that of the guinea pig. The changes displayed were an overall increased thickness, with typical submucosal edema but only slight epithelial reaction. In comparison with previous results with lidocaine, phenol and Bonain's solution, Emla seemed to be harmless to the structure of the TM. However, the efficacy of Emla as a topical TM anesthetic remains to be proved in future clinical trials.
    Type of Medium: Electronic Resource
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  • 166
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    Medical & biological engineering & computing 26 (1988), S. 267-270 
    ISSN: 1741-0444
    Keywords: Compliance ; Curve fitting ; Rat ; Stepwise cystometry ; Urinary bladder ; Viscoelasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The urinary bladder of the rat was examined by nearly ideal, unit step volume infusions. Spontaneous detrusor contractions occurred in vivo but ceased soon after death. A hydrodynamic model of the post mortem bladder wall was evaluated. Elastic properties were described by introducing two types of compliances; a dynamic compliance for fast response characteristics and a static compliance for the relaxed bladder wall. These compliances were easy to measure and found to vary with the degree of bladder expansion. The influence of viscosity was well described by a model with two relaxation time constants and was the optimal model in almost 50 per cent of the measurements. The long time constant was found to increase with bladder expansion.
    Type of Medium: Electronic Resource
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  • 167
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    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 6 (1988), S. 585-592 
    ISSN: 0736-0266
    Keywords: Bone cement ; Antibiotics ; Biodegradable ; Rat ; Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An experimental biodegradable bone cement [poly(propylene fumarate)-methylmethacrylate] (PPF-MMA) has been compared in vivo with polymethylmethacrylate (PMMA) as a carrier agent for local release of antibiotics. This approach is potentially applicable to the treatment of chronic osteomyelitis where the clinical goal is to achieve sustained high concentrations of antibiotics locally in the infected bone. In our experiments, gentamicin- and vancomycin-impregnated cylindrical PMMA and PPF-MMA cement specimens were implanted subcutaneously in rats, and blood and wound fluid samples were obtained over a 2-week period. Antibiotic levels were determined using immunoassays, and microbiologic activity was confirmed with agar diffusion techniques. The biodegradable PPF-MMA cement achieved and maintained considerably higher wound antibiotic levels than did PMMA cement. Vancomycin levels for the PPF-MMA cement were greater than 20 times those for the PMMA cement at all sampling times from 24 h to 14 days. For both cements, the serum antibiotic concentrations remained safely below maximum levels recommended for parenteral therapy. Mechanical testing of the PPF-MMA cement showed that admixture of 3% by weight of antibiotic did not adversely affect material properties. We conclude that this experimental biodegradable bone cement (PPF-MMA) can be used as a carrier to achieve high sustained local levels and low serum levels of antibiotics. Because it is biodegradable and thus does not require a secondary procedure for removal, it has special potential for use in treatment of chronic osteomyelitis.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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