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  • rat  (8)
  • Springer  (8)
  • American Physical Society
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  • 1
    ISSN: 1573-904X
    Schlagwort(e): intracerebral microdialysis ; blood-brain barrier ; hypertonic opening ; atenolol, pharmacokinetics ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The aim of this study was to determine whether changes in the transport of drugs into the brain could be determined by in vivo intracerebral microdialysis. Atenolol was used as a model drug to determine blood-brain barrier (BBB) transport characteristics. In rats, unilateral opening of the blood-brain barrier was achieved by infusion of hyperosmolar mannitol (25%, w/v) into the left internal carotid artery. BBB transport, expressed as the ratio of the area under the curve (AUC) of atenolol in brain extracellular fluid over plasma, was three times higher for the mannitol treated hemisphere as compared with the contralateral brain or after infusion of saline, being (mean ± SEM) 0.094 ± 0.024 (n = 16), 0.029 ± 0.007 (n = 12) and 0.030 ± 0.009 (n = 12) respectively. Further evaluation of the data indicated that for experiments performed in the morning the mannitol infusion had little effect on the extent of transport of atenolol into the brain, while in the afternoon BBB transport was about 10-fold higher than in the contralateral and saline group. The mean “afternoon” ratios ± SEM were 0.155 ± 0.038 (n = 8), 0.012 ± 0.003 (n = 6) and 0.018 ± 0.006 (n = 6) respectively. It is concluded that intracerebral microdialysis is capable of revealing changes in BBB transport and regional and time-dependent differences in drug levels can be demonstrated with the use of this technique.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1572-8773
    Schlagwort(e): copper deficiency ; Cytochrome c oxidase ; heart ; mitochondria ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Copper deficiency has been reported to be associated withdecreased cytochrome c oxidase activity, whichin turn may be responsible for theobserved mitochondrial impairment and cardiac failure. We isolatedmito-chondriafrom hearts of copper-deficient rats: cytochrome c oxidase activity was found to be lowerthan incopper-adequate mitochondria. The residual activity paralleled coppercontent of mitochondria and also corresponded with the heme amount associated with cytochromeaa3. In fact, lower absorption in thea-band region of cytochrome aa3 was foundfor copper-deficient rat heart mitochondria. Gel electrophoresisof protein extractedfrom mitochondrial membranes allowed measurements of protein content of thecomplexes ofoxidative phosphorylation, revealing a lower content of complex IV protein incopper-deficientrat heart mitochondria. The alterations caused by copper deficiency appear to bespecific forcytochrome c oxidase. Changes were not observed for F 0 F 1 ATP synthase activity,for heme contents ofcytochrome c and b, and for protein contents of complexes I, III and V.The present study demonstrates that the alteration of cytochrome c oxidase activityobserved in copper deficiency is due to a diminishedcontent of assembled protein and that shortnessof copper impairs heme insertion into cytochrome c oxidase.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    ISSN: 1573-4919
    Schlagwort(e): sphingomyelinase ; Mn2+-activated ; rat ; seminiferous tubules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Mammalian sphingomyelinases have been implicated in many important physiological and pathophysiological processes. The seminiferous tubules of immature (19 day-old) Wistar rats have at least three types of sphingomyelinases, a lysosomal one and two microsomal ones. One of the microsomal sphingomyelinases is active at pH 6.5 and is stimulated by Mn2+ 〉 Co2+ 〉 Mg2+, and the other is active at pH 7.4 and is stimulated by Mn2+ 〉 Mg2+ and inhibited by Co2+. The two microsomal enzymes are only slightly inhibited by EDTA and at pH 7.4 the stimulatory effects of Mn2+ and Mg2+ are additive. These data characterize the existence of two different membrane-bound sphingomyelinases in the seminiferous tubules of the rat.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    ISSN: 1573-4919
    Schlagwort(e): acute pancreatitis ; caerulein ; CCK receptor antagonists ; hydrocortisone ; rat ; zymogen granules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract Little is known about the changes in pancreatic enzyme storage in acute pancreatitis. We have performed flow cytometric studies of zymogen granules from rats with acute pancreatitis induced by hyperstimulation with caerulein. A comparison was made with rats treated with hydrocortisone (10 mg/kg/day) over 7 days before inducing pancreatitis in order to find out whether the amount of enzymes stored in the pancreas plays a key role in the development of pancreatitis. The potentially therapeutic effect of L-364,718 (0.1 mg/kg/day, for 7 days), a CCK receptor antagonist, was assayed in the rats with caerulein-induced pancreatitis which had previously received the hydrocortisone treatment. A significant increase in the intragranular enzyme content was observed 5 h after hyperstimulation with caerulein. The highest values were reached in the rats previously treated with hydrocortisone. The greatest pancreatic enzyme load was parallel to the highest values in plasma amylase, edema and haematocrit observed. Acute pancreatitis was reversed seven days later. At this stage smaller granules appeared in the pancreas whose enzyme content was similar to that of controls when no treatment was applied after pancreatitis. In contrast, L-364,718 administration prevented the favourable evolution of pancreatitis since the antagonism exerted on CCK receptors induced a blockade of secretion of the large amounts of enzymes stored in the pancreas. Moreover, the enzyme content in zymogen granules was below normal values since the stimulatory CCK action on enzyme synthesis can be inhibited by L-364,718. Our results suggest that the efficiency of CCK antagonists, as potential therapy, would also depend on the load of enzymes in the pancreas when acute pancreatitis is produced.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    ISSN: 1573-4978
    Schlagwort(e): dexamethasone ; gender ; MRF genes ; mRNA expression ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Muscle formation and postnatal growth is under the control of the muscle regulatory factors (MRF) gene family, consisting of four genes: MyoD1, myogenin, myf-5, and myf-6. Muscle mass is also known to be affected by specific drugs, like glucocorticoids. Glucocorticoids have also been characterized as muscle atrophying agents. However, glucocorticoids are also the only drugs reported to have a beneficial effect on the treatment of muscle degenerative disorders. Since muscle mass relates to gender, this may be partially caused by gender. The aim of this study is to investigate gender-related basal and dexamethasone-induced expression of the MRF genes. Gender-specific MRF mRNA levels were investigated in anterior tibial muscles of the rat. Myogenin, myf-5, and myf-6 mRNA level was significantly higher in female rats than in male rats. Since muscle mass is usually higher in males, we conclude that the development of gender-related differences in muscle mass is not primarily under the control of the mRNA levels of the MRF genes. Male rats treated with dexamethasone for 14 days (1 mg per kg body weight) showed increased levels of MyoD1, myogenin and myf-5 compared to control male rats. Female rats treated with dexamethasone showed decreased expression of myf-6 compared to control female rats. These results suggest that dexamethasone increase satellite cell-specific MRF activity in male muscle tissue, which is suggested to be associated with muscle hypertrophy, while maintenance of muscle tissue is affected in female muscle tissue. Therefore, we conclude that both basal and dexamethasone-induced MRF gene mRNA levels are regulated gender-specific.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    ISSN: 1573-4986
    Schlagwort(e): acute pancreatitis ; zymogen granule glycoconjugates ; Cholecystokinin-receptor antagonist ; rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Lectin-binding studies have been performed on rat zymogen granules to investigate alterations in the carbohydrate membrane composition that occur in acute pancreatitis induced by caerulein. The influence of treatment with hydrocortisone for seven days before inducing pancreatitis was also studied. Lectin labeling on zymogen granules was also analyzed seven days after inducing pancreatitis in rats that had previously received a hydrocortisone treatment. During this period L 364,718 (0.1 mg/kg)—specific cholecystokinin (CCK) receptor antagonist—was administered daily to some of the rats, and no treatment was applied to others. Using fluorescein-labelled T. purpureus (TP)lectin, a significant decrease in the amount of L-fucose in the granule membrane was observed in rats with caerulein-induced pancreatitis. This effect was directly caused by the pancreatitis and was not influenced by previous hydrocortisone treatment. Seven days later, the density of TP receptors in the granule membrane was similar to the controls both in L-364,718-treated and untreated rats. Therefore, we suggest that endogenous CCK is not an essential factor in the recovery of L-fucose containing glycoconjugates the granule membrane after pancreatitis. Acute pancreatitis did not alter the expression of wheat germ agglutinin (WGA) receptors in the zymogen granule membrane. WGA specifically binds N-acetyl glucosamine and sialic acids. L 364,718 administered for seven days after inducing pancreatitis significantly reduced WGA binding, untreated rats showed a normal zymogen granule membrane. Therefore, the blockade of CCK-induced alterations in membrane glycoconjugates enriched in N-acetyl glucosamine and sialic acid of newly formed granules after pancreatitis, a finding that could explain the delay in the regression of the disease.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    ISSN: 1573-904X
    Schlagwort(e): etomidate ; pharmacokinetics ; pharmacodynamics ; rat ; electroencephalogram
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The effect-plasma concentration relationship of etomidate was studied in the rat using electroencephalographic changes as a pharmacodynamic parameter. Methods. Etomidate was infused (50 mg/kg/h) in chronically instrumented rats (n = 6) until isoelectric periods of 5 s or longer were observed in the electroencephalogram (EEG). The EEG was continuously recorded during the experiment and frequent arterial blood samples were taken for determination of etomidate plasma concentrations. The changes observed in the raw EEG signal were quantified using aperiodic analysis in the 2.5−7.5 Hz frequency band. The return of the righting reflex was used as another parameter of anesthesia. Results. A mean dose of 8.58 ± 0.41 mg/kg needed to be infused to reach the end point of 5 s isoelectric EEG. The plasma concentration time profiles were most adequately fitted using a three-exponential model. Systemic clearance, volume of distribution at steady-state and elimination half-life averaged 93 ± 6 ml/min/kg, 4.03 ± 0.24 l/kg and 59.4 ± 10.7 min respectively. The EEG effect-plasma concentration relationship was biphasic exhibiting profound hysteresis. Semi-parametric minimization of this hysteresis revealed an equilibration half-life of 2.65 ± 0.15 min, and the biphasic effect-concentration relationship was characterized nonparametrically by descriptors. The effect-site concentration at the return of the righting reflex was 0.44 ± 0.03 μg/ml. Conclusions. The results of the present study show that the concentration-effect relationship of etomidate can be characterized in individual rats using aperiodic analysis in the 2.5−7.5 Hz frequency band of the EEG. This characterization can be very useful for studying the influence of diseases on the pharmacodynamics of etomidate in vivo.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular neurobiology 16 (1996), S. 345-356 
    ISSN: 1573-6830
    Schlagwort(e): rat ; genetic selection ; development ; maternal deprivation ; stress ; brain ; dopamine ; corticosteroid hormones
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary 1. The stress response system is shaped by genetic factors and life experiences, of which the effect of a neonatal life event is among the most persistent. Here we report studies focused on the “nature-nurture” question using rat lines genetically selected for extreme differences in dopamine phenotype as well as rats exposed as infants to the traumatic experience of maternal deprivation. 2. As key to the endocrine and behavioural adaptations occurring in these two animal models the hormone corticosterone (CORT) is considered. The stress hormone exerts slow and persistent genomic control over neuronal activity underlying the stress response system via high affinity mineralocorticoid (MR) and glucocorticoid receptors (GR). This action is exerted in a coordinate manner and involves after stress due to the rising CORT levels progressive activation of both receptor types. 3. Short periods of maternal separation (neonatal handling) trigger subsequently enhanced maternal care and sensory stimulation. However, a prolonged period (24h) of depriving the infant of maternal care disrupts the stress hyporesponsive period (SHRP) and causes an inappropriate rise in CORT. During development exposure to CORT and to sensory stimulation has long-lasting consequences for organization of the stress response system. 4. We find that these factors embodied by mother-pup interaction are critical for dopamine phenotype, CORT receptor dynamics and neuroendocrine regulation in adult life. The findings provide a conceptual framework to study dopamine-related psychopathology against a background of genetic predisposition, early life events, stress hormones and brain development.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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