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  • 1995-1999  (707)
  • 1997  (707)
  • Industrial Chemistry  (437)
  • Human  (145)
  • Rat
  • Nuclear reactions
  • 1
    ISSN: 1530-0358
    Schlagwort(e): Rat ; Intraperitoneal ; 5-Fluorouracil ; Chlorhexidine ; Perforated colorectal cancer ; Recurrence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract PURPOSE: Colorectal cancer is a prevalent and mortal disease, resulting in nearly 55,000 deaths in the United States annually. Preoperative or intraoperative spillage of tumor cells because of perforation occurs in up to 10 percent of cases. When this spillage occurs, the chance of recurrence and death is dramatically increased. METHODS: In an effort to reduce the chance of recurrence and death, we used a rat model to evaluate the efficacies of intraperitoneal 5-fluorouracil and chlorhexidine in reducing the incidence of recurrence. Rats were injected with 10 mg/kg azoxymethane subcutaneously weekly for 12 weeks to induce colorectal cancers. At 20 weeks, subtotal colectomies were performed on rats with colorectal tumors and without peritoneal implants or liver metastases. At the time of surgery, a cut portion of the tumor was placed in the abdomen for 30 minutes; the rats then randomly received peritoneal irrigation with 5-fluorouracil, chlorhexidine, or sterile water (control). Eight weeks postoperatively a necropsy was performed. At that time, obvious and suspected recurrences and the anastomotic area were sampled for histologic evaluation. RESULTS: Significant differences were seen with chlorhexidine vs.water for gross tumor (P=0.05) and microscopic tumor (P 〈0.05). 5-Fluorouracil showed a greater rate of abscess formation vs.both control and chlorhexidine (P 〉0.05). CONCLUSIONS: Use of chlorhexidine intraperitoneal therapy at the time of the operation for perforated colorectal cancer significantly decreases the frequency of gross tumor recurrence but not total recurrences. Intraperitoneal 5-fluorouracil does not significantly decrease recurrence and may increase the risk of abscess when used intraoperatively.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1438-8359
    Schlagwort(e): Protein C ; Cardiac arrest ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 3
    ISSN: 1435-1803
    Schlagwort(e): Rat ; collagen ; developed pressure ; pressure-volume relationships ; extracellular matrix
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objectives: The impact of acute collagen disruption by the disulfide donor, 5,5′-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts.Methods: Collagen was degraded acutely in 13 isolated, isovlumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control).Results: Collagen content was 3.5±0.5% of ventricular dry weight in control group compared with 2.1±0.4% in DTNB group (decrease by 40%, p〈0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86±17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68±13% (p〈0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15±8 mmHg in control and 30±13 mmHg (p〈0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63±0.26 in control to 6.07±0.11 (p〈0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function.Conclusions: These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 166-172 
    ISSN: 1432-1912
    Schlagwort(e): Key words Catalepsy ; VM nucleus ; Kainic lesions ; Pontine reticular formation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Bilateral kainic acid lesions of the ventro-medial (VM) thalamic nucleus of rats which greatly reduced the catalepsy produced by haloperidol (2 mg/kg i.p.) not only did not reduce, but even enhanced, the cataleptogenic effect of eserine (1 mg/kg i.p.) and arecoline (30 mg/kg i.p.). This finding is in accord with former conclusions that catalepsy produced by cholinergic drugs does not depend on striatal mechanisms. In rats with kainic acid lesions of the VM thalamic nucleus, and similarly in intact, non-lesioned rats, systemic administration of eserine and arecoline potentiated the catalepsy produced by microinjections of carbachol (2 μg) into the pontine reticular formation (PRF). Atropine microinjected bilaterally into the PRF attenuated the cataleptogenic effect of eserine and arecoline i.p. We suggest that the PRF is a site at which systemically given cholinergic drugs act to produce catalepsy.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 364-367 
    ISSN: 1432-1912
    Schlagwort(e): Key words Capsaicin ; CGRP (calcitonin ; gene-related peptide) ; Endothelium-dependent ; relaxation ; Thoracic aorta ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Previous studies have shown that pretreatment with calcitonin gene-related peptide (CGRP), a principal transmitter in sensory nerves, can protect the endothelial cell. We therefore evaluated whether in vivo capsaicin treatment prevents endothelial damage elicited by lysophosphatidylcholine (LPC) in the rat aorta. Acute treatment or repeated pretreatment with capsaicin resulted in stimulation of neurotransmitter release from sensory nerves or depletion of their transmitter content respectively. Vasodilator responses to acetylcholine (ACh) were examined in the aorta of these animals. Acute application of capsaicin (50 mg/kg) increased the plasma concentration of CGRP-like immunoreactivity (CGRP-LI) concomitantly with a reversal of the inhibition by LPC of endothelium-dependent ACh-induced relaxation in the isolated rat aorta. After repeated pretreatment with capsaicin to deplete sensory nerve neurotransmitter content the effects of capsaicin were absent as shown by the plasma CGRP-LI concentration and the vasodilator response to ACh. The results demonstrate that systemic capsaicin treatment, which evokes the release of CGRP from sensory nerves, protects the endothelial cell. The present study also suggests that CGRP may be an endogenous vascular protective substance.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-1912
    Schlagwort(e): Key words Neuropeptide Y (NPY) ; Ca2+ efflux ; Y1 receptor ; Na+/Ca2+ exchange ; Na+ influx ; Cardiomyocyte ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Several physiological stimuli cause a rise in intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes. This increased [Ca2+]i must be restored to physiological resting level to ensure response to further stimuli. In the present study, we examined the effect of neuropeptide Y (NPY), which is secreted from certain adrenergic or non-adrenergic neurons, on Ca2+ efflux from freshly isolated, quiescent adult rat cardiomyocytes. The isolated cardiomyocytes were preloaded with 45CaCl2 for 1 h. Then, the fractional release of 45Ca2+ from the cells was measured. NPY stimulated the efflux of 45Ca2+ from isolated adult rat cardiomyocytes in a concentration-dependent manner (10–8 M to 10–6 M). NPY (10–6 M)-induced Ca2+ efflux was 2.0 ± 0.16% of the total cellular content. The 45Ca2+ efflux from the cells was also stimulated by Y1 receptor agonist, [Leu31, Pro34]NPY, but not by Y2 receptor agonist, NPY13–36. The effect of NPY was inhibited by a peptide NPY inhibitor, NPY18–36 and a non-peptide NPY inhibitor, benextramine to a similar extent. From these results, it is conceivable that the effect of NPY on Ca2+ efflux from cardiomyocytes is mediated through Y1 receptors. It was also observed that NPY caused a rise in [Ca2+]i to almost 150 nM. NPY-stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. Moreover, NPY caused a 22Na+ influx into the cells of about 1.6-fold over the basal value which was inhibited by amiloride and 5-(N,N-dimethyl)-amiloride, known Na+/Ca2+ exchange inhibitors. In addition, isoproterenol also caused 45Ca2+ efflux from the cells and which was enhanced by the addition of NPY. These results suggest that NPY stimulates extracellular Na+-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on plasma membrane Y1 receptors with which NPY may couple during Na+/Ca2+ exchange.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-1912
    Schlagwort(e): Key words Airway smooth muscle ; Human ; Guinea-pig ; Potassium channels ; NO-donor ; β2-adrenoceptor-agonist
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In human bronchi, relaxations to salbutamol and sodium nitroprusside were performed in the presence or absence of blockers of the large Ca2+-activated K+-channels (BKCa): charybdotoxin (Chtx), iberiotoxin (Ibtx) or tetraethylammonium (TEA). In bronchi under basal tone in presence of indomethacin (1 μM) or precontracted with acetylcholine (in presence or absence of indomethacin), the relaxations to salbutamol or sodium nitroprusside were unaffected or weakly inhibited by pretreatment with the BKCa blockers (Chtx (100 nM), Ibtx (100 and 300 nM) and TEA (1 mM)). Significant inhibitions were mainly observed with TEA (1 mM) and iberiotoxin at high concentration (300 nM). These results contrasts with the potent inhibitory effects exerted by Chtx (100 nM) or Ibtx (100 nM) in guinea-pig trachea precontracted with acetylcholine in absence or presence of indomethacin indicating that human airways are less susceptible to BKCa blockade than guinea-pig airways. In addition, the BKCa blockers induced slowly developing contractions of human bronchi at basal tone. The contraction induced by TEA (1 mM) was abolished by verapamil (10 μM) suggesting that BKCa blockade promotes an increase in membrane Ca2+-conductance through activation of voltage-gated Ca2+-channels. Verapamil also reversed the effects of TEA on salbutamol-induced relaxations in human bronchi as well as the effects of Ibtx on salbutamol- or sodium nitroprusside-induced relaxations in guinea-pig trachea. These data suggest that BKCa blockers induce activation of voltage-gated Ca2+-channels and therefore influx of Ca2+ which in turn cause a functional antagonism of β2-adrenoceptor-agonist- and NO-donor-induced relaxations. Moreover, the BKCa opener, NS-1619, induced weak relaxations in human bronchi and guinea-pig trachea which were not blocked by TEA or Ibtx suggesting that BKCa opening is of minor significance for the relaxation of human airway smooth muscles. In conclusion, although a wealth of studies have demonstrated that β-adrenoceptor agonists or NO-donors activate BKCa, the present study provides evidence that in human bronchi, as recently suggested in guinea-pig trachea, opening of BKCa does not appear to functionally participate in the relaxation to these relaxant agents.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-1912
    Schlagwort(e): Key words Antimigraine drugs ; Arteriovenous ; anastomoses ; Avitriptan ; BMS-180048 ; Carotid artery ; Human ; Human coronary artery ; Migraine ; Pig ; Sumatriptan
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Several acutely acting antimigraine drugs, including ergotamine and sumatriptan, have the ability to constrict porcine arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of avitriptan (BMS-180048; 3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-N-methyl-1H-indole-5-methanesulfonamide monofumarate), a new 5-HT1B/1D receptor agonist. In anaesthetized pigs, avitriptan (10, 30, 100 and 300 μg·kg–1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was increased. The mean ± SEM i.v. dose of avitriptan eliciting a 50% decrease (ED50) in the porcine carotid arteriovenous anastomotic blood flow was calculated to be 76 ± 23 μg·kg–1 (132 ± 40 nmol·kg–1) and the highest dose (300 μg·kg–1) produced a 72 ± 4% reduction. In recent comparative experiments (DeVries et al. 1996), the mean ± SEM ED50 (i.v.) of sumatriptan in decreasing carotid arteriovenous anastomotic blood flow was 63 ± 17 μg·kg–1 (158 ± 43 nmol·kg–1), with a reduction of 76 ± 4% by 300 μg·kg–1, i.v. Both avitriptan (pD2: 7.39 ± 0.09; Emax: 13.0 ± 4.5% of the contraction to 100 mM K+) and sumatriptan (pD2: 6.33 ± 0.09; Emax: 15.5 ± 2.3% of the contraction to 100 mM K+) contracted the human isolated coronary artery. The above results suggest that avitriptan should be able to abort migraine headaches in patients, but may exhibit sumatriptan-like effects on coronary arteries. Initial clinical studies have demonstrated the therapeutic action of the drug in acute migraine.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1912
    Schlagwort(e): Key words 5-Hydroxytryptamine ; 5-HT1A receptors ; Microdialysis ; Flesinoxan ; WAY 100635 ; 8-OH-DPAT ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K+ and perfusion with Ca2+-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT1A receptors.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-0843
    Schlagwort(e): Key words Anthracyclines ; Daunorubicin ; Daunorubicinol ; Pharmacokinetics ; Rat ; Aging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Age-related differences in pharmacokinetics may be important in determining altered anthracycline cardiotoxicity in the senescent rat and also in older humans. This study examined the effect of aging on daunorubicin pharmacokinetics in the Fischer 344 rat. Daunorubicin 7.5 mg/kg was administered i.v. to 6-and 24-month-old male Fischer 344 rats and plasma and tissue sampling was performed over 168 h for assay of daunorubicin and daunorubicinol concentrations by high-performance liquid chromatography. Systemic clearance of daunorubicin was decreased in older compared to younger animals (56±4 versus 202±17 ml min-1 kg-1; P〈0.05). In addition, the area under the plasma daunorubicinol concentration/time curve was significantly increased in older rats. In the heart, the area under the concentration/time curve was significantly increased in senescence both in the case of daunorubicin (201±12 versus 86±4 μg h g-1; P〈0.05) and daunorubicinol (1347±118 versus 182±4 μg h g-1; P〈0.05). Furthermore, the peak mean concentrations of daunorubicin were increased in older compared to younger rats both in plasma (1078±82 versus 663±66 ng ml-1; P〈0.05) and in heart (27±1 versus 10±1 μg g-1; P〈0.05). This also was true for daunorubicinol in plasma (284±39 versus 168±27 ng ml-1; P〈0.05) and in myocardium (8.6±0.6 versus 2.4±0.2 μg g-1; P〈0.05). Following daunorubicin injection, the ratio of daunorubicinol to daunorubicin concentrations in tissues increased with time, particularly in plasma and heart in senescent rats. Thus, there are significant age-related changes in daunorubicin and daunorubicinol kinetics in the rat that could alter susceptibility to acute systemic toxicity and to chronic cardiotoxicity.
    Materialart: Digitale Medien
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  • 11
    ISSN: 1433-2981
    Schlagwort(e): Peripheral blood ; Progenitor cells ; Rat ; Stem cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The assay system for determination of haemopoietic progenitors in peripheral blood of rats is essen tial for potential studies on mobilisation and transplantation of circulating progenitor cells in a rat experimental model. This paper demonstrates the possibility of detection and quantification of pluripotent progenitors (Colony Forming Units-Spleen day 8-CFU-Sd8) and committed progenitors (Colony Forming Units Granulocyte Macrophage-CFU-GM and Burst Forming Units-Erythroid-BFU-E) in peripheral blood of rats in a steady state. For determination of CFU-Sd8 the ‘rat to mouse’ in vivo assay was used, and for committed progenitors in vitro assays on methylcellulose were employed. The CFU-Sd8 incidence ranged from 7.3 to 11.6/ml of rat blood, similar to that reported in literature for mice. The incidence of CFU-GM was found to be 59.7 ± 9.4/ml which is in the range of the literature data for mice, rabbits, dogs and humans. The incidence of BFU-E in rat peripheral blood was 4.3 ± 1/ml, which was relatively low, but could be also considered as comparable with some literature data for dogs and humans. The CFU-E were not detected by the technique used. These results confirmed the existence of circulatory blood pluripotent progenitors (CFU-Sd8) and committed (CFU-GM and BFU-E) progenitors in rat, as has been established for some other mammalian species.
    Materialart: Digitale Medien
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  • 12
    ISSN: 1434-0879
    Schlagwort(e): BBN ; Bladder tumor ; Rat ; Endoscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recent advances in tumor carbohydrate biochemistry have demonstrated antitumor effects of locally administered GM3 ganglioside on mouse MBT-2 tumor. When intravesical therapy inN-butyl-N(4-hydroxybu-tyl)nitrosamine (BBN)-induced rat bladder tumor is attempted, it is essential to identify the tumor, to classify its size before therapy and to monitor the effect of the therapy. To establish a more reliable experimental therapeutic system, we assessed the development of BBN-induced rat bladder tumor by endoscopic observation. BBN-induced bladder tumors in rats were observed serially using a 4.2-F flexible fiberscope. The endoscopic findings were compared with the histopathological findings. Intravesical tumor growth varied greatly between individual rats. The smallest change detected by endoscopy was a small edematous lesion histologically proved to be papilloma. The largest nodular lesion was determined to be a papillary, transitional cell carcinoma. This noninvasive method makes the BBN rat experimental system more reliable by allowing confirmation of tumor formation and classification of the tumor volume prior to therapy.
    Materialart: Digitale Medien
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  • 13
    ISSN: 1434-0879
    Schlagwort(e): Renal cell carcinoma ; Renal tubular transport ; Renal cortical slices ; p-Aminohippurate ; Human ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In vitro accumulation ofp-aminohippurate (PAH) was investigated in “intact” human renal cortical slices of normal kidney tissue and in tissue slices of renal cell carcinoma (RCC). The technique used was established in preliminary experiments on rat kidney tissue slices. In principle, the accumulation capacity is comparable in renal tissue slices of both species (slice to medium accumulation ratios between 4 and 8). In man sex differences in accumulation capacity do not exist. But, as shown in detail for rats, accumulation capacity drops with age. Tissue slices of RCC are unable to accumulate PAH actively; slice to medium ratio reaches about 1 and indicates passive PAH uptake only. Surprisingly, in tumors of stage pTl PAH uptake is lowest, perhaps as a sign of PAH transport out of the cells. There is no difference between peripheral and central parts of RCC. Age and sex are without influence on PAH uptake in RCC tissue slices. Interestingly, the accumulation capacity of “intact” tissue of kidneys infested with RCC also depends on the severity of the tumor (stage, diameter), but not on grading and formation of metastases.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 25 (1997), S. 173-177 
    ISSN: 1434-0879
    Schlagwort(e): αB crystallin ; Heat shock protein ; Rat ; Kidney neoplasms
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of two small stress proteins, αB crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of αB crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P 〈 0.0001). In contrast, HSP27 concentrations in both renal cell (mean ± SD: 1790 ± 940 ng/mg protein,n = 15) and mesenchymal (1260 ± 1080 ng/mg protein,n = 10) tumors were significantly higher than the normal kidney value (142 ± 30 ng/mg protein,n = 10,P 〈 0.0001). A positive correlation was found between αB crystallin and HSP27 levels limited to the renal cell tumor case (Pearson's correlation coefficient,r = 0.68,P 〈 0.01). Immunohistochemistry revealed the loops of Henle to be positive for αB crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for αB crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 25 (1997), S. 199-206 
    ISSN: 1434-0879
    Schlagwort(e): Pig ; Human ; α2-Adrenoceptor ; β-Adrenoceptor ; Bladder ; Prostate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have quantified and characterized α1-, α2-and β-adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. α1-, α2- and β-adrenoceptor were identified in radioligand binding studies using [3H]prazosin, [3H]RX 821002 and [125I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance β 〉 α2 ≫ α1 (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was β 〉 α2 ≫ α1 (not detectable) and β ≫ α1 〉 α2. respectively. The α2-adrenoceptors in all tissues were homogeneously of the α2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The β-adrenoceptors represented a mixed population with a dominance of the β2-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.
    Materialart: Digitale Medien
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  • 16
    ISSN: 0942-0940
    Schlagwort(e): Rat ; brain injury ; diffuse injury ; free radicals ; lipid peroxidation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Free radicals are generated after head injury. These radicals rapidly react with polyunsaturated fatty acids in the cell membrane and cause membrane destruction. This process is called lipid per-oxidation. Malondialdehyde (MDA) is one of the end products of lipid peroxidation, and it is a frequently used indicator of lipid per-oxidation in biological tissues. Using a diffuse head injury animal model, we studied the time course of lipid peroxidation in different regions of injured rat brains. In the present study, the MDA levels were 36.7%, 41.8%, and 35.1% greater than sham at one hour after injury at the frontal, parietal, and brain stem, respectively (p〈0.0001). The MDA levels in these regions continued to increase and peaked a 4 hours after the injury. The levels slowly decreased, and by 24 hours, they were still significantly higher than the sham control's. The elevation of MDA levels was less in the striatum and the temporal regions at one hour. They were 16.9% and 13.3%, respectively (p〈0.002). The MDA levels in these two regions continued to increase even after 4 hours of injury, but the degree of elevation never exceeded 35%. The results demonstrate that there is an immediate, posttraumatic burst of MDA production, suggesting the formation of free radicals after diffuse head injury. Even though all the regions sampled show the same effect, certain regions are less affected by this diffuse head injury animal model.
    Materialart: Digitale Medien
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  • 17
    ISSN: 1432-0533
    Schlagwort(e): Key words Schwann cell ; Diabetic neuropathy ; Human ; Animal model ; Galactose ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Despite early descriptions of hypertrophic Schwann cells and onion-bulb formation in patients with diabetic neuropathy, clinical and experimental studies have emphasized axonal pathology. In recent years, the Schwann cell has been further implicated in diabetic neuropathy because it is the primary intrafascicular location for the first enzyme of the polyol pathway, aldose reductase, which appears to have a role in modulating a variety of complications of diabetes, including diabetic neuropathy. To further explore the role of polyol pathway flux in the pathogenesis of Schwann cell injury, ultrastructural abnormalities of Schwann cells in human diabetic neuropathy (HDN) were compared with those in experimental galactose neuropathy (EGN), a well-characterized model of hyperglycemia without hypoinsulinemia. Similar to previous studies of EGN, reactive, degenerative and proliferative changes of Schwann cells were observed after 2, 4 and 24 months of galactose intoxication. Reactive changes included accumulation of lipid droplets, π granules of Reich and glycogen granules, increased numbers of subplasmalemmal vesicles, cytoplasmic expansion, and capping. Degenerative changes included enlargement of mitochondria and effacement of cristae, and disintegration of both abaxonal and adaxonal cytosol and organelles. Both demyelination and onion-bulb formation were seen at all time points, although supernumerary Schwann cells and axonal degeneration were most numerous after 24 months of galactose feeding. In sural nerve biopsy samples from patients with diabetes and progressive worsening of neuropathy, ultrastructural abnormalities in Schwann cells encompassed the full range of reactive, degenerative and proliferative changes described in galactose-fed rats. The concordance of fine-structural observations in nerves from galactose-fed rats and these adult-onset diabetic patients emphasizes the role of flux through aldose reductase in the complex pathology of diabetic neuropathy and points to the utility of galactose intoxication in helping to understand this metabolic disorder.
    Materialart: Digitale Medien
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  • 18
    ISSN: 1432-0533
    Schlagwort(e): Key words Microwave irradiation ; Mobile telephony ; Blood-brain barrier ; Vasogenic edema ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.
    Materialart: Digitale Medien
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  • 19
    ISSN: 1432-0533
    Schlagwort(e): Key words Traumatic brain injury ; Hypothermia ; Fluid percussion ; Rat ; Contusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Early outcome measures of experimental traumatic brain injury (TBI) are useful for characterizing the traumatic severity as well as for clarifying the pathomechanisms underlying patterns of neuronal vulnerability. However, it is increasingly apparent that acute outcome measures may not always be accurate predictors of chronic outcome, particularly when assessing the efficacy of potential therapeutic regimens. This study examined the chronic histopathological outcome in rats 8 weeks following fluid-percussive TBI coupled with moderate post-traumatic brain hypothermia, a protocol that provides acute neuronal protection. Animals received a moderate parasagittal percussive head injury (2.01–2.38 atm) or sham procedure followed immediately by 3 h of brain hypothermia (30°C) or normothermia (37°C). Eight weeks following TBI, serial tissue sections were stained with hematoxylin and eosin or immunostained for glial fibrillary acidic protein. Tissue damage, gliosis and immunoreactive astrocytes were observed in the ipsilateral thalamus, hippocampus, and in the neocortex lateral to the injury site. Within the thalamus, focal necrosis was restricted to selective thalamic nuclei. Significant hippocampal cell loss was found in the ipsilateral dentate hilar region of both TBI groups. Quantitative volume measurements revealed significant decreases in cortical, thalamic and hippocampal volume ipsilateral to the impact in both TBI groups. Lateral ventricles were substantially enlarged in the TBI-normothermia group, an effect which was significantly attenuated by post-TBI hypothermia. The attenuation of lateral ventricular dilation by post-traumatic hypothermia is indicative of chronic neuroprotection in this TBI model. These data provide new information concerning the chronic histopathological consequence of experimental TBI and the relevance of this trauma model to chronic human head injury.
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 93 (1997), S. 494-500 
    ISSN: 1432-0533
    Schlagwort(e): Key words Cystatins ; Transthyretin ; Brain tumors ; Pituitary adenomas ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The localization of cystatin C (CC) and transthyretin (TTR) synthesis was studied using Northern blot and immunohistochemical methods. Normal brain tissues from all sites studied contained CC mRNA. Immunoreactive CC was present in the choroid plexus epithelial cells, cerebral and cerebellar neurons, astrocytes, ependymal cells, macrophage-like cells of the arachnoid membrane and in neuroendocrine cells of the anterior pituitary lobe. TTR mRNA and TTR were restricted to the choroid plexus. In primary brain tumors, the transcript for CC was found in all 39 tumors examined, while the protein could only be demonstrated in 3/5 choroid plexus papillomas, 8/8 astrocytomas, 7/23 anaplastic astrocytomas and glioblastomas, 1/6 oligodendrogliomas, 1/1 oligoastrocytoma, 1/4 anaplastic oligodendrogliomas, 3/7 ependymomas, 0/1 anaplastic ependymoma, 0/5 primitive neuroectodermal tumors, 0/1 neuroblastoma, 3/11 meningiomas and 16/16 pituitary adenomas. CC cannot be used as a marker for any specific brain tumor type but the fact that the protein could be demonstrated more frequently in astrocytomas than in their more malignant counterparts suggests that the cellular production and secretion of CC changes with the malignant progression of these tumors. TTR mRNA and TTR were present only in the choroid plexus papillomas, indicating that TTR synthesis is mainly restricted to such brain neoplasms.
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  • 21
    ISSN: 1432-0533
    Schlagwort(e): Key words Intercellular adhesion molecule 1 ; Immunohistochemistry ; Rat ; Brain ; Trauma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A study was made on the expression of the intercellular adhesion molecule 1 (ICAM-1) in cerebral microvessels after cortical contusion trauma of the rat brain. The trauma was produced by a free-falling weight on the exposed dura of one fronto-parietal lobe. Immunohistochemistry was done on cryostat sections using a monoclonal antibody and the reaction product was visualized using the avidin-biotin-peroxidase complex method. Control and sham-operated rats showed immunostaining of some penetrating arteries of the cerebral cortex, the epithelial cells of the choroid plexus and occasional microvessels of the brain parenchyma. The same pattern of immunostaining was seen in rats that were subjected to trauma and killed after 30 min. All rats with contusion trauma that were allowed to survive for 6–72 h showed a substantial increase in the number of immunostained capillaries throughout the site of the lesion. The ipsilateral hippocampus showed a mild to moderate increase in the number of immunostained microvascular profiles. This phenomenon was also present in the lateral thalamus of some rats. The staining was seen as an uninterrupted line at the position of the endothelial cells, indicating an up-regulation of this adhesion molecule after brain trauma. Up-regulation of ICAM-1 is a well-known phenomenon in inflammatory and ischemic lesions of the brain but has not previously been described in detail in traumatic brain injury. ICAM-1 may be involved in the production of several post-traumatic events such as leukocyte adhesion, microcirculatory disturbances and edema formation.
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  • 22
    ISSN: 1432-0533
    Schlagwort(e): Key words Parkinson’s disease ; Neural transplantation ; Allogeneic ; Major histocompatibility complex antigens ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neural transplantation, as a therapeutic approach to Parkinson’s disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-μl macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3–6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.
    Materialart: Digitale Medien
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  • 23
    ISSN: 1432-069X
    Schlagwort(e): Key words Tape stripping ; Human ; Stratum corneum ; Penetration studies ; Skin furrows
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Tape stripping of human stratum corneum is widely used as a method for studying the kinetics and penetration depth of drugs. Several factors can influence the quantity of stratum corneum that is removed by a piece of tape, such as the manner of tape stripping, the hydration of the skin, cohesion between cells, body site and interindividual differences. However, few data are available about the influence of furrows in the human epidermis on the tape-stripping technique. In this study, we investigated the efficacy of tape stripping in removing complete cell layers from the superficial part of the human stratum corneum. A histological section of skin that was tape-stripped 20 times clearly showed nonstripped skin in the furrows, indicating persistent incomplete tape stripping. Replicas of tape-stripped skin surface demonstrated that even after removing 40 tape strips the furrows were still present. We validated the tape-stripping method further with X-ray microanalysis in the mapping mode by scanning electron microscopy, using a TiO2-containing compound as a marker. TiO2 applied to the skin before the tape-stripping procedures was still present after the tenth tape strip, and was specifically located on the rims of the furrows. We emphasize that results from studies using the tape-stripping method have to be viewed from the perspective that cells on one tape strip of the stratum corneum may be derived from different layers, depending on the position of the tape strip in relation to the slope of the furrow, and such results should be interpreted with considerable caution.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 196 (1997), S. 417-426 
    ISSN: 1432-0568
    Schlagwort(e): Key words Neuronal plasticity ; Fiber growth ; Regeneration ; Rat ; CNS myelin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  After lesions in the central nervous system (CNS), the affected nerve fibers usually cannot regenerate and reconnect to their original target cells. One important reason for this failure to regenerate is the presence of neurite growth inhibitory molecules in the myelin sheath of central nerve fibers. Despite the absence of regeneration fiber growth can occur after CNS lesions from intact nerve fibers unaffected by the lesion. These fibers can form new collaterals and sprout into the region denervated by the lesion, thereby increasing their terminal arbors in a process called collateral sprouting. A certain functional compensation for the nerve fibers lost by the lesion can be achieved by this mechanism. In the spinal cord, collateral sprouting is extensive after lesions in young postnatal animals and decreases with increasing age. In the spinal cord of adult animals, axon sprouting can be observed but is strongly restricted. The factors that determine the amount of sprouting found after lesions at different ages are still largely unknown. Recent evidence suggests that the myelin-associated neurite growth inhibitors that suppress regeneration also restrict collateral sprouting in the spinal cord. In addition, the expression of growth-associated molecules, in particular the growth-associated protein GAP-43, by the sprouting nerve fibers appears to be an important determinant of the sprouting response. The robustness of the sprouting response is thus likely to be controlled by intrinsic growth determinants of the sprouting neuron as well as by the growth promoting and growth inhibitory properties of the microenvironment of the sprouting fibers.
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  • 25
    ISSN: 1432-069X
    Schlagwort(e): Key words Viability ; Hairless mouse skin ; Human ; neonatal skin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background and design: Viable tissue is essential to assess the rate and extent of biotransformation during percutaneous absorption in vitro. We assessed the viability of hairless mouse whole skin (WS) and stratum corneum/epidermis (SCE) and human neonatal SCE following separation from the dermis by EDTA phosphate-buffered saline (EDTA-PBS) incubation or by heat treatment by measuring the conversion of dextrose to lactate. Lactate concentrations in receptor fluid samples were determined using a Sigma diagnostic lactate determination kit. A standard curve was prepared and samples assayed spectrophotometrically at 340 nm using a lambda 2β spectrophotometer. Standard curves were prepared for each experiment and correlation coefficient values ( r ) were calculated. Results: Our results showed that heirless mouse SCE was associated with glucose conversion to lactic acid at an increased rate if incubated in EDTA-PBS for 4 h and used immediately. Lactate production was greater with the dermis present (EDTA-PBS WS). The rate of glucose to lactate conversion in hairless mouse SCE was 20–25% of that found in WS. Compared with Dulbecco’s modified PBS (DMPBS)-treated WS controls, the rate of lactate production in EDTA-PBS-treated WS was nearly a 50% less. Heat treatment in water at 60° C to separate SCE from hairless mouse WS appeared to eliminate viability. Viability of hairless mouse SCE, as measured by glucose conversion to lactate, was comparable to human neonatal SCE. Conclusions: These results suggest that the dermis is a significant contributor to glucose metabolism and that incubation in EDTA-PBS is a contributing factor to the overall decrease in metabolic capacity of the tissue. As a result of these findings, hairless mouse SCE appears to be useful as a model for human neonatal SCE in percutaneous absorption studies.
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    Archives of dermatological research 289 (1997), S. 466-470 
    ISSN: 1432-069X
    Schlagwort(e): Key words Alopecia areata ; Human ; Hair ; Cytokines ; Adhesion molecules ; MHC molecules ; Diphenylcyclopropenone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The immune response present in untreated alopecia areata (AA) is characterized by overexpression of ICAM-1 and MHC molecules on dermal papilla cells of affected hair follicles and by a distinct cytokine pattern. After successful treatment with the potent contact allergen diphenylcyclopropenone (DCP), adhesion molecules are downregulated and a reversed pattern of cytokines is expressed. To determine which cytokines may be involved in this process we studied the expression and modulation of ICAM-1 and MHC class I and II molecules on cultured dermal papilla cells. Scalp biopsies were obtained from healthy donors and dermal papillae were isolated. The cells were treated with various cytokines and prostanoids. The surface molecules were labeled with FITC-conjugated antibodies, and the expression levels were quantified by FACScan analysis. Incubation with IFN-γ led to a time-dependent upregulation of the surface molecules studied. IL-1β and TNF-α synergistically increased the expression of ICAM-1, but they failed to induce MHC molecules. However, both cytokines significantly reduced the IFN-γ-induced HLA-DR expression. Pretreatment of cells with the cyclooxygenase inhibitor diclofenac, prostanoids, IL-10 or TGF-β1 did not alter the constitutive or IFN-γ-elicited expression of surface molecules. A neutralizing anti-IL-1β-antibody did not affect any cytokine-induced changes. We conclude that with regard to surface molecules we can partly imitate in vitro the situation of AA in vivo. Moreover, our results suggest that TNF-α, which is markedly increased under DCP treatment, might be an effector of the therapeutic response in AA.
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    Archives of dermatological research 289 (1997), S. 506-513 
    ISSN: 1432-069X
    Schlagwort(e): Key words Hydration ; Confocal laser scanning ; microscopy ; refractive index ; Image analysis ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of this study was to characterize the swelling behaviour of the stratum corneum. Stratum corneum pieces isolated from the breast region of 20 different females were incubated in distilled water at two different temperatures (20° C and 45° C) for 90 min and 24 h, respectively. Half of the stratum corneum pieces were previously extracted with chloroformmethanol (2 : 1). The area-enlargement was photographically recorded. The thickness enlargement was determined using a confocal laser scanning microscope. The average swelling (99% confidence interval) in the area dimension at 20° C was 8.4% ± 1.4% (n = 20), which corresponded to an average swelling in the length (lateral) dimension of approximately 4.1%. The swelling in the thickness dimension was 26.3% ± 16.3% (n = 8). The swelling was most pronounced in the thickness dimension and was complete after 90 min of water immersion (P 〈 0.01, n = 5). In addition, the removal of the intercellular lipids with chloroform/methanol (2 : 1) induced a decreased swelling in the samples (P 〈 0.01, n = 20). An increase in temperature of the water from 20° C to 45° C resulted in an increase in swelling (P 〈 0.01, n = 20). Taken together our results support the idea that the mechanism of stratum corneum swelling is linked to the intercellular lipid structure and hence to skin barrier function.
    Materialart: Digitale Medien
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Hematology and cell therapy 38 (1997), S. 241-246 
    ISSN: 1279-8509
    Schlagwort(e): Human ; Bone marrow ; Fibroblasts ; Proliferation ; Cytokines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Bone marrow fibroblasts regulate hematopoiesis by interacting directly (cell-to-cell contact) with hematopoietic cells and by secreting regulatory molecules (such as GM-CSF, M-CSF, IL6 and LIF) that modulate hematopoiesis either in a positive or a negative manner. Several cytokines (such as bFGF, EGF, PDGF and TGF-ß) affect the growth of human marrow fibroblasts in vitro. Further in vivo studies are still required to clarify the role of marrow fibroblasts and their interactions with hematopoietic progenitors during myelofibrosis and leukemic diseases.
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  • 29
    ISSN: 1279-8517
    Schlagwort(e): Human ; “Hamstrings” ; Nerve and vascular supply ; Fecal incontinence ; Muscle transposition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Résumé La graciloplastie électro-stimulée est utilisée de plus en plus fréquemment dans le traitement chirurgical de l'incontinence anale. L'utilisation d'un autre muscle peut être intéressante si le muscle gracile n'est pas utilisable. 30 muscles semitendineux et 15 longs chefs du biceps fémoral ont été étudiés sur des cadavres humains. Ce travail a porté particulièrement sur l'innervation et la vascularisation de ces muscles, dont dépendent les possibilités de transposition. Le long chef du m. biceps fémoral recevait sa vascularisation principale de la première et de la deuxième artère perforante et son innervation d'une branche motrice venant du nerf sciatique, tel que cela est décrit dans la littérature. L'étude du m. semitendineux a montré de nouveaux aspects anatomiques dans sa vascularisation. Dans tous les cas ce muscle recevait sa vascularisation principale de l'artère circonflexe médiale près de la tubérosité ischiatique et de la deuxième a. perforante. Son innervation venait de deux branches motrices du nerf sciatique. Ces deux muscles répondaient aux critères nécessaires pour leur transposition comme néo sphincter. Cependant, compte-tenu de sa vascularisation et de son innervation, le m. semitendineux répond mieux aux impératifs anatomiques que le long chef du biceps et représente une alternative au muscle gracile pour la création d'un néo sphincter anal.
    Notizen: Summary Anal neosphincter formation with electrically stimulated gracilis muscle is used increasingly for the surgical treatment of fecal incontinence. An alternative to gracilis might be of interest if this muscle is not available. 30 semitendinosus muscles and 15 long heads of biceps femoris were investigated on human cadavers. In particular, the nerve and vascular supply of these muscles was studied, both representing basic factors for muscle transposition. The long head of biceps femoris m. was found to receive its dominant vascular supply from the first and second perforating artery and its nerve supply from one motor branch out of the sciatic nerve, both as described in literature. The examination of semitendinosus m., however, revealed new anatomical aspects in its vascular supply. In all cases semitendinosus m. was found to receive dominant vascular pedicles from the medial circumflex femoral artery close to the ischial tuberosity and the second perforating artery. The nerve supply consisted of two motor branches out of the sciatic nerve. Both muscles fulfilled several basic criterias for transposition to the anus. However, regarding these requirements, semitendinosus offered distinct advantages in comparison with the long head of biceps femoris. Due to its vascular and nerve topography, semitendinosus seems suitable to serve as an alternative to gracilis.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Intensive care medicine 23 (1997), S. 896-902 
    ISSN: 1432-1238
    Schlagwort(e): Key words Tetanus ; Intrathecal ; Baclofen ; Benzodiazepine ; GABA ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objective: Spasms in patients with generalized tetanus can be suppressed by a spinal intrathecal infusion of baclofen. We report on four patients and review reported cases treated by this method elsewhere. Design: Intrathecal baclofen infusion was started with a bolus dose (300–500 μg) and continued at a steady rate of 500–1000 μg/day. The dose was increased in daily steps as needed. Results: Doses of baclofen of 500, 1000, or 2000 μg/day were effective in three patients, while 1500 μg/day was insufficient in the fourth. Bradycardia and hypotonia occurred in one patient at a dose of 2000 μg/day but resolved after the dose was reduced to 1500 μg/day. Another patient developed hypotonia when a bolus of 500 μg was given after a steady infusion of 1500 μg/day. Voluntary movements were preserved in one and returned in two patients when sedation, induced by initial diazepam infusions, receded. The fourth patient needed diazepam during most of the treatment with intrathecal baclofen and required mechanical ventilation while being treated with baclofen. Conclusions: A catheter position higher than T11 would possibly have yielded better results. It may be necessary to adapt the dose during the course of the illness. The preservation of respiratory drive and voluntary movements is the main advantage of treating tetanus with intrathecal baclofen. Additionally it helps to reduce sympathetic hyperactivity. Mortality may thereby be reduced.
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  • 31
    ISSN: 1432-1106
    Schlagwort(e): Transplant ; Striatum ; Substantia nigra ; Patch-matrix ; Regeneration ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract When patients with Parkinson’s disease initially show symptoms, approximately 80–85% of their dopaminergic nerve fibers in the striatum have degenerated. It is thus of importance to develop strategies to try to rescue the remaining dopaminergic neurons and to stimulate them to induce sprouting. In this study the goal was to examine whether the different subgroups of dopaminergic neurons in the ventral mesencephalon projecting to the basal ganglia have different sprouting capacities when stimulated by the trophic effect of a fetal striatal graft. Lateral ganglionic eminence was implanted into the lateral ventricle, the midportion of dorsal striatum, globus pallidus, or ventral striatum. Solid tissue pieces from 13- to 15-mm fetuses were stereotactically implanted into adult female Sprague-Dawley rats. At postgrafting week 4 the animals were perfused and processed for tyrosine hydroxylase (TH) immunohistochemistry. Transplants placed in the lateral ventricle were TH-negative, except for two cases with TH-positive fibers where the ependymal layer was disrupted, thereby allowing direct contact between the graft and the adjacent host striatum. The transplants placed into dorsal striatum were innervated by small patches of dopaminergic nerve fibers. Areas between the TH-positive patchy structures remained TH-negative. In grafts placed into globus pallidus, both patchy structures and a less dense TH-positive nerve fiber network was noted. The TH-positive growth pattern in transplants placed in ventral striatum was also devided into patchy and widespread growth. Grafts placed in globus pallidus and ventral striatum revealed significantly larger areas of TH-positive innervation compared with that measured in grafts placed in dorsal striatum and the lateral ventricle. In conclusion, it is possible to induce sprouting of TH-immunoreactive nerve fibers from all areas examined. The most potent areas to initiate dopaminergic growth were the globus pallidus and ventral striatum, where both a patchy dense and a widespread, less dense growth was induced. Thus, if using a trophic stimulus to induce sprouting from remaining dopaminergic nerve fibers in Parkinson’s disease, the preferential target to induce sprouting would be ventromedial striatum and growth would be guided toward dorsal striatum owing to the enhanced dopaminergic growth properties in the ventromedial areas.
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  • 32
    ISSN: 1432-1106
    Schlagwort(e): Auditory cortical activation ; Speech ; Monaural stimulation ; Cerebral blood flow ; Positron emission tomography ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To investigate how auditory input from each ear contributes to spoken language processing, cortical activation by monaural speech sound stimulation was examined in 12 normal subjects using15O-labeled water positron emission tomography. Regional cerebral blood flow (rCBF) was measured under four different sound stimulation conditions: (1) silence, (2) white noise, (3) sequential Japanese sentences (“speech”), and (4) Japanese sentences played backward (“reversed speech”), and the results were evaluated by statistical parametric mapping (SPM). Noise induced significant rCBF increase in the contralateral Heschl’s gyrus. Speech and reversed speech stimuli caused significant rCBF increase in the contralateral Heschl’s gyrus and the bilateral superior temporal gyri, with contralateral activation broader than that in the ipsilateral hemisphere. Monaurally input speech sound signals that reach the contralateral Heschl’s gyrus may be processed chiefly and phonologically in the surrounding superior temporal gyrus in the same hemisphere. Comparison of speech activation with reversed speech activation failed to demonstrate a significant difference, which made it difficult to identify the area for lexical and semantic processing.
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  • 33
    ISSN: 1432-1106
    Schlagwort(e): GABA ; Double immunostaining ; Retrograde tracing ; Diagonal band ; Disinhibition ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the septal complex, both parvalbumin and calbindin neurons cocontain GABA. In the same area, a large number of GABA-GABA synaptic connections can be observed. In order to further characterize their neurochemical nature, as well as the extrinsic and/or intrinsic origin of these GABA terminals, the following experiments were performed: (1) correlated light- and electronmicroscopic double immunostaining for calbindin and parvalbumin on septal sections of control rats; (2) light microscopic parvalbumin immunostaining of septal sections after surgical isolation (5 days) of the septum from its telencephalic or (3) hypothalamic afferents; and (4) parvalbumin immunostaining of sections prepared from the entire brain 2 days following horseradish peroxidase injection into the border between the lateral and medial septum. The results demonstrated that: (1) in a well-circumscribed, vertically longitudinal area located between the lateral and medial septum, 0.1–0.6 mm anterior to the bregma, a group of calbindin-containing, nonsomatospiny neurons are surrounded by parvalbumin-immunoreactive baskets; (2) these basket-forming axon terminals establish symmetric synaptic contacts with their targets; and (3) their cells of origin are not in the medial septum, but in the angular porition of the vertical limb. These observations indicate that a portion of the septal complex GABA-GABA synaptic connections represent functional interaction between two different types of GABAergic neurons. The presynaptic GABAergic neurons contain parvalbumin, and the postsynaptic GABAergic cells are immunoreactive for calbindin. Furthermore, a population of the medial septum/diagonal band parvalbumin neurons promect only to the hippocampus, while others, which may also send axons to the hippocampus, terminate on lateral septum calbindin cells as well.
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  • 34
    ISSN: 1432-1106
    Schlagwort(e): Kinesthesia ; Coordination ; Cerebellum ; Muscle spindles ; Cutaneous mechanoreceptors ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A coordinated triggering task requiring use of kinesthetic information was employed to assess the timing of use of kinesthetic information in normal subjects and patients with cerebellar dysfunction. Passive movements of varying velocity were imposed in the flexor direction about the metacarpophalangeal joint of the right index finger. Subjects attempted to depress a switch with their left thumb when the index finger moved, past a specified angle that was learned during a training session. The velocities ranged from 10°/s to 88°/s in 2°/s increments. After 200 trials, subjects were then instructed instead to react as quickly as possible (reaction-time task) to the onset of movement for an additional 200 trials. For the same movements, the timing of onset of responses of muscle spindle afferents and cutaneous mechanoreceptors was determined by recording the responses of these afferents using microneurography. For slow velocities, patients were able to perform similarly to normals but at faster velocities patients triggered too late compared with normals. Patients required more time to use kinesthetic information than did normal subjects. An estimate of kinesthetic processing was not longer in patients. The chief explanation for the prolonged time required to use kinesthetic information in patients was that their reaction times were prolonged by 93 ms. In addition, the movement time was also prolonged, but this accounted for only 23 ms. Impaired motor performance in tasks requiring the use of kinesthetic information in cerebellar patients can be explained largely by their prolonged reaction times. Muscle spindle afferents responded on average much sooner than cutaneous mechanoreceptors. Because of the limited time available to perfomr the kinesthetic triggering task, the role for cutaneous mechanoreceptors, to provide singals for on-line coordination of movement appears limited compared with muscle spindle afferents.
    Materialart: Digitale Medien
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 303-310 
    ISSN: 1432-1106
    Schlagwort(e): Hippocampus ; Adenosine A1 receptor ; DPCPX ; Purines ; Membrane partitioning ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Despite its potent proconvulsant effects in vitro, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) does not induce seizures when administered in vivo. This contrasts with the effects of less selective adenosine antagonists such as theophylline or cyclopentlytheophylline, and led us to reexamine the nature of DPCPX-induced epileptiform activity. In the present study, we report that proconvulsant effects of bath-applied DPCPX in rat hippocampal slices are only observed after a preceding stimulus such as NMDA receptor activation or brief tetanic stimulation. While this may be due to the absence of a basal “purinergic tone”, the relatively high interstitial concentrations of adenosine present in the slice suggest that access of the drug to A1 receptors may instead be prevented by tightly coupled endogenous adenosine, with the ternary adenosine-A1 receptor-G protein complex stabilised in the high-affinity conformation by a coupling cofactor. This implies that a substantial percentage of adenosine A1 receptors are inactive under physiological conditions, but that access of adenosine A1 receptor antagonists may be facilitated under pathological conditions. Once induced, DPCPX-evoked spiking persists for long periods of time. A “kindling” effect of A1 receptor blockade is unlikely, since persistent spiking is not usually observed with less selective A1 antagonists even after prolonged application. Alternatively, endogenous adenosine released during increased neuronal activity may activate A2 receptors during selective A1 blockade. The most important factor determining the duration of DPCPX-induced spiking, however, may be a persistence of the drug in the tissue and subsequent access to the A1 receptor via a membrane-delineated pathway, since DPCPX-induced spiking could be shown to decrease markedly after a transient superfusion of theophylline. This hypothesis, which implies that the apparent affinity of adenosine antagonists for the A1 receptor is in part a function of their membrane partitioning coefficient, is supported by a close correlation between alkylxanthine logP values obtained from the literature and theirK i value at A1 receptors, but not at the enzyme phosphodiesterase, whose xanthine binding site is presented to the cytosol. The implications for the therapeutic value of purinergic drugs are discussed.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 343-352 
    ISSN: 1432-1106
    Schlagwort(e): Memory ; Glutamate receptors ; GABA receptors ; Modulatory sites of NMDA receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Effects of redox reagents on excitatory and inhibitory synaptic responses as well as on the bidirectional plasticity of α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) andN-methyl-d-aspartate (NMDA) receptor-mediated synaptic responses were studied in CA1 pyramidal neurons in rat hippocampal slices. The oxidizing agent 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB, 200 μM) did not affect AMPA, GABAA or GABAB receptor-mediated synaptic responses or the activation of presynaptic metabotropic receptors. However, DTNB irreversibly decreased (by approximately 50%) currents evoked by focal application of NMDA. DTNB also decreased the NMDA component of the EPSC. The reversal potential of NMDA currents and the Mg2+ block were not modified. In the presence of physiological concentrations of Mg2+ (1.3 mM), DTNB did not affect the NMDA receptor-dependent induction of long-term potentiation (LTP) or long-term depression (LTD) expressed by AMPA receptors. In contrast, DTNB fully prevented LTP and LTD induced and expressed by NMDA receptors. Plasticity of NMDA receptor-mediated synaptic responses could be reinstated by the reducing agenttris-(2-carboxyethyl) phosphine (TCEP, 200 μM). These results suggest that persistent, bidirectional changes in synaptic currents mediated by NMDA receptors cannot be evoked when these receptors are in an oxidized state, whereas NMDA-dependent LTP and LTD are still expressed by AMPA receptors. Our observations raise the possibility of developing therapeutic agents that would prevent persistent excitotoxic enhancement of NMDA receptor-mediated events without blocking long-term modifications of AMPA receptor-mediated synaptic responses, thought to underlie memory processes.
    Materialart: Digitale Medien
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  • 37
    ISSN: 1432-1106
    Schlagwort(e): Key words Perinatal asphyxia ; Apoptosis ; Necrosis ; Hematoxylin-eosin ; DNA fragmentation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The consequences of perinatal asphyxia on the rat brain were studied 80 min to 8 days after birth with hematoxylin-eosin and in situ DNA double-strand-breaks labeling histochemistry. Asphyxia was induced by immersing fetus-containing uterus horns, removed from ready-to-deliver Sprague-Dawley rats, in a water bath at 37°C for various time periods (0–22 min). Spontaneous- and cesarean-delivered pups were used as controls. Perinatal asphyxia led to a decrease in the rate of survival, depending upon the length of the insult. No gross morphological changes could be seen in the brain of either control or asphyctic pups at any of the studied time points after delivery. However, in all groups, nuclear chromatin fragmentation, corresponding to in situ detection of DNA fragmentation, was observed at different stages. Nuclear fragmentation in control pups showed a specific distribution that appeared to be related to brain maturation, thus indicating programmed cell death. A progressive and delayed increase in nuclear fragmentation was found in asphyctic pups, which was dependent upon the length of the perinatal insult. The most evident effect was seen in frontal cortex, striatum, and cerebellum at postnatal day 8, although changes were also found in ventral-posterior thalamus, at days 1 and 2. Thus, nuclear chromatin fragmentation in asphyctic pups indicates a delayed post-asphyctic neuronal death. The absence of signs of inflammation or necrosis suggests that delayed neuronal cell death following perinatal asphyxia is an active, apoptosis-like phenomenon.
    Materialart: Digitale Medien
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 137-146 
    ISSN: 1432-1106
    Schlagwort(e): Key words Arm aiming movements ; Fitts’ law ; Context dependency ; Sequential action ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Arm movements in the horizontal plane consisting of two segments were examined to determine whether the difficulty of the second segment influenced the kinematic characteristics of the first segment. The direction of the first segment was an elbow extension movement away from the trunk and remained constant throughout the experiment. The direction of the second segment varied between forearm extension and flexion movements. Based on Fitts’ law, two different indexes of difficulty (ID) of the second segment were utilized by changing target size and movement amplitude. The effects of changing ID were examined for two different movement amplitudes. All movements were single-joint movements employing elbow flexion/extension and were recorded by an x-y digitizer. Variations in the ID of the second segment produced context-dependent kinematic changes in the performance of the initial segment. Movement duration increased when the ID was increased by reducing target size for both extension-extension sequence and extension-flexion sequences. Peak velocity also decreased for higher ID targets in the extension-flexion sequence. However, there was an interaction between the ID and movement amplitude in the extension-flexion sequence. In this sequence the duration of movement for the high ID/large movement amplitude condition increased substantially compared with the low ID/small movement amplitude condition. In addition, changing ID of the second segment influenced the time between the two segments (intersegment interval) in the extension-flexion sequence. Collectively, these data suggest that the planning of complex movements is based in part on the accuracy demands of multiple segments of the sequence.
    Materialart: Digitale Medien
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  • 39
    ISSN: 1432-1106
    Schlagwort(e): Key words Sensorimotor control ; Centripetal gating ; Tibial nerve ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Attenuation of initial somatosensory evoked potential (SEP) gain becomes more pronounced with increased rates of movement. Manipulation of the range of movement also might alter the SEP gain. It could alter joint receptor discharge; it should alter the discharge of muscle stretch receptors. We hypothesized that: (1) SEP gain reduction correlates with both the range and the rate of movement, and (2) manipulation of range and rate of movement to achieve similar estimated rates of stretch of a leg extensor muscle group (the vasti) results in similar decreases in SEP gain. SEPs from Cz’, referenced to Fpz’ (2 cm caudal to Cz and Fpz, respectively, according to the International 10–20 System), along with soleus H-reflexes were elicited by electrical stimulation of the tibial nerve at the popliteal fossa. Stable magnitudes of small M-waves indicated stability of stimulation. A modified cycle ergometer with an adjustable pedal crank and electric motor was used to passively rotate the right leg over three ranges (producing estimated vasti stretch of 12, 24 and 48 mm) and four rates (0, 20, 40 and 80 rpm) of movement. Two experiments were conducted. Ranges and rates of pedalling movement were combined to produce two or three equivalent estimated rates of tissue stretch of the vasti muscles at each of 4, 16, 32 and 64 mm/s. Tibial nerve stimuli were delivered when the knee was moved through its most flexed position and the hip was nearing its most flexed position. Means of SEP, H-reflex and M-wave magnitudes were tested for rate and range effects (ANOVA). A priori contrasts compared means produced by equivalent estimated rates of vasti stretch. Increasing the rate of movement significantly increased the attenuation of SEP and H-reflex gain (P〈0.05). Increasing the range of movement also significantly increased these gain attenuations (P〈0.05). Combining these to achieve equivalent rates of stretch, through different combinations of rate and range, resulted in equivalent depressions of SEP gain. H-reflex gains were similarly conditioned. These results suggest that muscle stretch receptors play a more important role than joint or cutaneous receptors in regulating SEP gain consequent to movement. We note that the present calculation only considers the knee extensors; however, the biomechanical model of stretch applies also to receptors in the hip extensors. This paper and the companion one show that primary factors in the kinaesthetic components of the movement regulate activity-induced gain attenuation of SEPs.
    Materialart: Digitale Medien
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 247-256 
    ISSN: 1432-1106
    Schlagwort(e): Key words Entorhinal cortex ; Subiculum ; Retrohippocampus ; Latent inhibition ; Partial reinforcement extinction effect ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Experiment 1 assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate.
    Materialart: Digitale Medien
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  • 41
    ISSN: 1432-1106
    Schlagwort(e): Key words Species differences ; CA2 ; Retrograde tracing ; Colocalization ; Theta rhythm ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Our recent studies showed the co-existence of substance P and calretinin in the supramammillo-hippocampal pathway of monkeys, as well as species differences in the synaptic targets of extrinsic substance P fibers in the hippocampi of monkeys and rats. Experiments used: (1) single and multiple stereotaxic injection of wheat germ agglutinin-conjugated HRP into the hippocampus and immunostaining for substance P in the supramammillary area; (2) colocalization of substance P and calretinin in supramammillary area cells; and (3) colocalization of these two neurochemicals in retrogradely labeled supramammillary projective cells of both male and female rats. These demonstrated: (a) many calretinin- and fewer substance P-immunoreactive neurons retrogradely labeled in the ipsilateral supramammillary area; (b) approximately 74% of all substance P cells contain calretinin and 9% of the calretinin neurons co-contain substance P; and, most importantly (c) none of the retrogradely labeled supramammillary cells colocalize calretinin and substance P. These results indicate the presence of two distinct supramammillo-hippocampal projections in the rat, one that contains substance P and the other calretinin. The latter innervates the same areas as those in the monkey, and the former terminates only in the CA2 hippocampal subfield.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 129-136 
    ISSN: 1432-1106
    Schlagwort(e): Key words Fos-like immunoreactivity ; Middle cerebral artery ; Focal cerebral ischaemia ; Spinal cord neurons ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study examined c-fos protein expression in the brain and spinal cord of rats following permanent occlusion of the middle cerebral artery (MCA) above the rhinal fissure. At 1 h after right-sided MCA occlusion, Fos-like immunoreactivity (Fos-LI) was detected in neurons not only in the ipsilateral cerebral cortex but also in the spinal cord. In the latter, Fos-LI was localized in the nucleus and perikarya of neurons in the grey matter, notably the large motor neurons in the ventral horn. Fos-LI was most intense at 2–4 h, but became undetectable after 48 h in the cerebral cortex and 72 h in the spinal cord. In sham-operated animals, Fos-LI was almost undetectable or virtually absent. It was also not detected in the core territory supplied by the MCA at any time points after arterial occlusion. When the ischaemia-induced neuronal damage in both the cerebral cortex and spinal cord was evaluated by Nissl staining, some neurons appeared atrophic. We conclude that the induction of Fos-LI in neurons of the cerebral cortex and spinal cord is linked respectively to early onset–short stimulation and persistent excitatory or disinhibition phenomenon as a result of focal ischaemic brain injury.
    Materialart: Digitale Medien
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 165-168 
    ISSN: 1432-1106
    Schlagwort(e): Key words Monosynaptic reflex ; Muscle afferents ; Motor unit ; Thumb ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The human thumb is controlled by a muscle, flexor pollicis longus (FPL), that is unique among mammals and contributes to manual dexterity. The present study sought to define whether the spinal reflex circuitry for this muscle differed from that for an adjacent muscle (flexor carpi radialis, FCR). In peri-stimulus time histograms, short-latency, largely monosynaptic excitation produced by median nerve stimulation was significantly less frequent and significantly smaller for FPL motor units than FCR motor units. Thus the motoneurone pools of adjacent muscles differ in their spinal reflex accessibility. The reflex control of FPL may thus be achieved by supraspinal pathways rather than the traditional monosynaptic arc.
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  • 44
    ISSN: 1432-1106
    Schlagwort(e): Key words Intersensory coordination ; Vision ; Proprioception ; Reaching movements ; Motor control ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  It is now well established that the accuracy of pointing movements to visual targets is worse in the full open loop condition (FOL; the hand is never visible) than in the static closed loop condition (SCL; the hand is only visible in static position prior to movement onset). In order to account for this result, it is generally admitted that viewing the hand in static position (SCL) improves the movement planning process by allowing a better encoding of the initial state of the motor apparatus. Interestingly, this wide-spread interpretation has recently been challenged by several studies suggesting that the effect of viewing the upper limb at rest might be explained in terms of the simultaneous vision of the hand and target. This result is supported by recent studies showing that goal-directed movements involve different types of planning (egocentric versus allocentric) depending on whether the hand and target are seen simultaneously or not before movement onset. The main aim of the present study was to test whether or not the accuracy improvement observed when the hand is visible before movement onset is related, at least partially, to a better encoding of the initial state of the upper limb. To address this question, we studied experimental conditions in which subjects were instructed to point with their right index finger toward their unseen left index finger. In that situation (proprioceptive pointing), the hand and target are never visible simultaneously and an improvement of movement accuracy in SCL, with respect to FOL, may only be explained by a better encoding of the initial state of the moving limb when vision is present. The results of this experiment showed that both the systematic and the variable errors were significantly lower in the SCL than in the FOL condition. This suggests: (1) that the effect of viewing the static hand prior to motion does not only depend on the simultaneous vision of the goal and the effector during movement planning; (2) that knowledge of the initial upper limb configuration or position is necessary to accurately plan goal-directed movements; (3) that static proprioceptive receptors are partially ineffective in providing an accurate estimate of the limb posture, and/or hand location relative to the body; and (4) that static visual information significantly improves the representation provided by the static proprioceptive channel.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 419-427 
    ISSN: 1432-1106
    Schlagwort(e): Key words Vestibular system ; Spatial orientation ; Motion perception ; Otolith-canal interaction ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Vestibular perception of whole-body passive rotation in the horizontal plane was studied by applying two-dimensional (2D) motion to eight blindfolded healthy volunteers: pure rotations in place, corner-like trajectories and arcs of a circular trajectory were randomly applied by means of a remotely controlled robot. Angles embedded in the 2D trajectories were 45°, 90°, 135° and 180°. Stimulation of semicircular canals was the same for all trajectories but was accompanied by concurrent otolith stimulation during circular motion. Subjects participated in two successive experimental sessions. In the first session they were instructed to use a pointer to reproduce the total angular displacement after the motion (REPRODUCTION); in the second session they had to keep pointing towards a remote (15 m) memorised target during the motion (TRACKING). In REPRODUCTION subjects tended to overestimate their rotation angle by 28 ± 11% (mean ± SD). There was no systematic effect of the trajectory. Overestimation also occurred when subjects were required to rotate in darkness by 180° (by controlling a joystick). In TRACKING there was virtually no overestimation (6 ± 17%) and the movement of the pointer matched the dynamics of angular motion. We conclude that (a) the brain can separate and memorise the angular component of complex 2D motion; however, a large inter-individual variability in estimating its amplitude exists; (b) in the range of linear accelerations used in the study, no appreciable effect of otolith-canal perceptual interaction was shown; (c) angular displacements can be dynamically transformed into matched pointing movements; (d) overestimation seems to be typical of delayed judgements of angular displacement and of self-controlled rotations in place. This could be due to the characteristics of the physiological calibration of the vestibular input.
    Materialart: Digitale Medien
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  • 46
    ISSN: 1432-1106
    Schlagwort(e): Key words Transcranial magnetic stimulation ; Transcranial electrical stimulation ; Motor cortex ; Inhibition ; Tibialis anterior ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The aim of the present study was to determine the characteristics of intracortical inhibition in the motor cortex areas representing lower limb muscles using paired transcranial magnetic (TMS) and transcranial electrical stimulation (TES) in healthy subjects. In the first paradigm (n=8), paired magnetic stimuli were delivered through a double cone coil and motor evoked potentials (MEPs) were recorded from quadriceps (Q) and tibialis anterior (TA) muscles during relaxation. The conditioning stimulus strength was 5% of the maximum stimulator output below the threshold MEP evoked during weak voluntary contraction of TA (33±5%). The test stimulus (67±2%) was 10% of the stimulator output above the MEP threshold in the relaxed TA. Interstimulus intervals (ISIs) from 1–15 ms were examined. Conditioned TA MEPs were significantly suppressed (P〈0.01) at ISIs of less than 5 ms (relative amplitude from 20–50% of the control). TA MEPs tended to be only slightly facilitated at 9-ms and 10-ms ISIs. The degree of MEP suppression was not different between right and left TA muscles despite the significant difference in size of the control responses (P〈0.001). Also, conditioned MEPs were not significantly different between Q and TA. The time course of TA MEP suppression, using electrical test stimuli, was similar to that found using TMS. In the second paradigm (n=2), the suppression of TA MEPs at 2, 3, and 4 ms ISIs was examined at three conditioning intensities with the test stimulation kept constant. For the pooled 2- to 4-ms ISI data, relative amplitudes were 34±6%, 61±5%, and 98±9% for conditioning intensities of 0.95, 0.90, and 0.85× active threshold, respectively (P〈0.01). In conclusion, the suppression of lower limb MEPs following paired TMS showed similar characteristics to the intracortical inhibition previously described for the hand motor area.
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 148-152 
    ISSN: 1432-1106
    Schlagwort(e): Key words Pointing ; On-line control ; Inverse kinematics ; Double-step stimulation ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The human arm is kinematically redundant, which may allow flexibility in the execution of reaching movements. We have compared reaching movements with and without kinematic redundancy to unpredictable double-step targets. Subjects sat in front of a digitising tablet and were able to view an arc of four targets reflected in the mirror as virtual images in the plane of the tablet. They were instructed to move, from a central starting point, in as straight a line as possible to a target. In one-third of trials, the target light switched to one of its neighbours during the movement. Subjects made 60 movements using shoulder, elbow and wrist and then another 60 movements in which only shoulder and elbow movement were allowed. By restraining the wrist, the limb was made non-redundant. The path length was calculated for each movement. In single-step trials, there was no significant difference between path lengths performed with and without wrist restraint. As expected there was a significant increase in path length during double-step trials. Moreover this increase was significantly greater when the wrist was restrained. The variability across both single- and double-step movements was significantly less while the wrist was restrained. Importantly the performance time of the movements did not alter significantly for single-step, double-step or restrained movements. These results suggest that the nervous system exploits the intrinsic redundancy of the limb when controlling voluntary movements and is therefore more effective at reprogramming movements to double-step targets.
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  • 48
    ISSN: 1432-1106
    Schlagwort(e): Key words Pain ; Capsaicin ; Cerebral blood flow ; Positron emission tomography ; Somatotopic organization ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Regional cerebral blood flow was measured with positron emission tomography (PET) in six healthy volunteers at rest and during experimentally induced, sustained cutaneous pain on the dorsum of the right hand or on the dorsum of the right foot. Pain was inflicted by intracutaneous injection of capsaicin, providing a mainly C-fibre nociceptive stimulus. Statistical analysis showed significant activations along the central sulcus (SI) area when comparing pain in the hand to pain in the foot. Separate comparison of both pain states to a baseline revealed different locations along the central sulcus for hand pain and foot pain. The encountered differences are consistent with what is previously known about the somatotopics of non-painful stimuli. When comparing painful stimuli to baseline, the contralateral anterior cingulate gyrus, the ipsilateral anterior insular cortex and the ipsilateral prefrontal cortex were implicated. The results are consistent with an involvement of SI in the spatial discrimination of acute cutaneous pain.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 525-538 
    ISSN: 1432-1106
    Schlagwort(e): Key words Walking ; Intentional on-line control ; Mechanical perturbation ; Neuromuscular synergy ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In locomotion, the capability to control and modulate intentionally the propulsive forces is fundamental for the adaptation of the body’s progression, both in speed and direction. The purpose of this experiment was to determine how human beings can achieve such control on-line. To answer this question, four subjects walking steadily were faced with a linear increase in resistance (impeding forward displacement), lasting 3 s, once per minute. At the end of the variation, the new resistance was maintained. There were two tasks; in both tasks, in the initial steady state, the subjects had to walk steadily at 1.3 m s–1. As the resistance increased, subjects were either required to maintain their walking speed (compensation task) or to let the walking speed and amplitude adapt freely (no-intervention task). This provided an estimate of the effects of the perturbation alone. Throughout the experiment, the stride frequency (114 step min–1) was fixed by a metronome. Subjects maintained their stride frequency on both tasks. In the no-intervention task, walking speed was 1.3 and 1 m s–1 under normal and high resistance respectively. In the compensation task, under high steady resistance, walking speed was maintained by an increase in the activation gain of the neuromuscular synergy: all recorded muscles increased their EMG activity, but without any change in the shape of their activation profile throughout the cycle. During the transitional phases, however, as the resistance began to increase, the walking speed decreased temporarily (–2%) before returning rapidly to its initial value. By contrast, at the end of the resistance increase, no such changes in speed were observed. During the transitional phases, the on-line compensation for the resistance increase induced modifications in the shape of the activation burst in the medial gastrocnemius such that the transitional cycles clearly differed from the steady state cycles. The results observed in the compensation task suggest that the subjects used two different modes of control during steady states and transitional phases. In stable dynamic conditions, there appears to be an ”intermittent control” mode, where propulsive forces are globally managed for the entire stance phase. As a result, no compensation occurred at the beginning of the perturbation. During the resistance increase, subjects appeared to switch to an ”on-line control” mode in order to continuously adapt the propulsive forces to the time course of the external force, resulting in an observable compensation at the end of the resistance change.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 153-157 
    ISSN: 1432-1106
    Schlagwort(e): Saccade ; Acceleration ; Eye ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pattern of acceleration was recorded during horizontal saccadic eye movements using a lightweight accelerometer fixed to a scleral contact lens. Horizontal saccades of 15–20° were dominated by either several pulses of acceleration, with a frequency of around 40 Hz, or a single acceleration-deceleration wave followed by lower amplitude polyphasic activity of about 80 Hz. These features are unlikely to be due to slippage or resonance in the contact lens-accelerometer system, as very similar patterns of acceleration were simultaneously recorded with an accelerometer taped over the closed eyelid of the contralateral eye. Analysis of simultaneous surface electromyogram recordings indicated that the multicomponent acceleration profiles were the product, at least in part, of the rhythmic and synchronous modulation of eye muscle discharge during saccades.
    Materialart: Digitale Medien
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 138-143 
    ISSN: 1432-1106
    Schlagwort(e): Parkinson’s disease ; Neural transplantation ; Cell death ; Lazaroid ; Dopamine ; Free radicals ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We explored the effects of congeners of nitrogen monoxide (NO) on cultured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the congeners of which have been found to exert either neurotoxic or neuroprotive effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitrosonium ion (NO+) is neuroprotective to cultured cortical neurons, we found that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment of dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical (NO) had presumably been formed. We also evaluated the effects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E exerted marked neuroprotective effects in both insult models. More than twice as many dopamine neurons (75% of control) survival when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U-83836E was added to cultures treated with SNP plus ascorbate. We conclude that the congeners of NO released by SNP are toxic to mesencephalic neurons in vitro and that the lazaroid U-83836E significantly increases the survival of dopamine neurons in situations where congeners of NO are generated.
    Materialart: Digitale Medien
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 207-213 
    ISSN: 1432-1106
    Schlagwort(e): Isometric finger force ; Sensorimotor integration ; Vibration ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The influence of afferent feedback on isometric fine force resolution was studied in humans. Subjects performed the smallest possible isometric flexion force increments with the index finger while visual, cutaneous, and muscle spindle feedback conditions were varied. In the control conditions with visual feedback, isometric force resolution was finest and independent of cutaneous or muscle spindle feedback. In the absence of visual cues, force resolution was significantly coarser. When agonist muscle spindles were vibrated (100 Hz and 150 Hz), fine force resolution capabilities declined further. Diminution of cutaneous feedback per se did not affect fine force resolution. However, the effect of agonist vibration was attenuated when full cutaneous feedback was available. We conclude that in voluntary isometric contractions the degree of fine force resolution depends on the type of afferent feedback available for calibrating central motor commands. Visual feedback is more powerful than spindle feedback, which is more efficient than cutaneous feedback. The extent to which the central motor command itself contributes to the sensation of force is indirectly implied by reproducible, yet coarser force resolution levels when peripheral information is minimized.
    Materialart: Digitale Medien
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  • 53
    ISSN: 1432-1106
    Schlagwort(e): Antidiuretic hormone ; Osmotic stimulus ; Anteroventral third ventricular region ; Prostaglandins ; Meclofenamate ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study explored the roles of prostaglandins in the anteroventral third ventricular region, a cerebral osmoreceptor site, in the osmoregulation mechanism of vasopressin release. We injected (1 μl) prostaglandin E2 (12.8 nmol) or meclofenamate (78.3 nmol), an inhibitor of prostaglandin biosynthesis, into the brain region or the lateral cerebral ventricle of conscious rats, examining their effects on plasma vasopressin and its controlling factors in the presence or absence of an osmotic stimulus. The injection of prostaglandin E2 into the anteroventral third ventricular region augmented plasma vasopressin and arterial pressure after 5 min and 15 min, without influencing plasma osmolality, sodium, potassium, or chloride. In contrast, intraventricular injection of prostaglandin E2 did not cause any significant effect on those variables. The i.v. infusion (0.1 ml·kg−1·min−1) of hypertonic saline (2.5 mol/l) enhanced plasma vasopressin after 15 min and 30 min; this was accompanied by increased plasma osmolality, sodium, and chloride, and by unaltered or elevated arterial pressure. Meclofenamate given into the anteroventral third ventricular region 30 min before starting the hypertonic saline infusion abolished the osmotic vasopressin response without significantly changing the responses of the other variables. Histological analysis showed that the injection sites of meclofenamate in these rats were close to those of prostaglandin E2 in the anteroventral third ventricular region and included the organum vasculosum of the lamina terminalis and the surrounding area, the medial preoptic area, and periventricular and median preoptic nuclei. When injection cannulae for meclofenamate deviated from those areas incidentally or when the drug was expressly administered into the cerebral ventricle, the osmotic vasopressin response was not inhibited. Plasma vasopressin and the other variables observed during the i.v. infusion of isotonic saline (0.15 mol/l) were not affected significantly by meclofenamate administration into the anteroventral third ventricular region or the cerebral ventricle. On the basis of these results, we concluded that prostaglandins synthesized in and/or near the anteroventral third ventricular region might contribute to the facilitation of vasopressin release in the hyperosmotic state.
    Materialart: Digitale Medien
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 235-245 
    ISSN: 1432-1106
    Schlagwort(e): Key words Manual prehension ; Visuomotor coordination ; Three-dimensional orientation ; Wrist joint ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  When reaching for an object, the proximity of the object, its orientation, and shape should all be correctly estimated well before the hand arrives in contact with it. We were interested in the effects of the object’s orientation on manual prehension. Subjects were asked to reach for an object at one of several possible orientations. We found that the trajectory of the hand and its rotation and opening were significantly affected by the object’s orientation within the first half of the movement. We also detected a slight delay of the wrist relative to the forearm and a small bias of the orientation of the fingers’ tips toward the orientation of the table on which the object lay. Finally, the aperture of the hand was proportional to the physical size of the object, which shows that size constancy was achieved from the variation of the object’s orientation. Taken together, these results indicate that the three components of the movement – the transport, rotation, and opening of the hand – have access to a common visual representation of the object’s orientation.
    Materialart: Digitale Medien
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 246-254 
    ISSN: 1432-1106
    Schlagwort(e): Key words Voluntary movement ; Hand ; Muscle spindle ; Fusimotor system ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Impulses of 16 muscle spindle afferents from finger extensor muscles were recorded from the radial nerve along with electromyographic (EMG) activity and kinematics of joint movement. Twelve units were classified as Ia and 4 as II spindle afferents. Subjects were requested to perform precision movements at a single metacarpophalangeal joint in an indirect visual tracking task. Similar movements were executed under two different conditions, i.e. with high and low error gain. The purpose was to explore whether different precision demands were associated with different spindle firing rates. With high error gain, a small but significantly higher impulse rate was found in pooled data from Ia afferents during lengthening movements but not during shortening movements, nor with II afferents. EMG was also significantly higher with high error gain in recordings with Ia afferents. When the effect of EMG was factored out, using partial correlation analysis, the significant difference in Ia firing rate vanished. The findings suggest that fusimotor drive as well as skeletomotor activity were both marginally higher when the precision demand was higher, whereas no indication of independent fusimotor adjustments was found. These results are discussed with respect to data from behaving animals and the role of fusimotor independence in various limb muscles proposed.
    Materialart: Digitale Medien
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 51-62 
    ISSN: 1432-1106
    Schlagwort(e): Key words Pupillary light reflex ; Pretectum ; Anterograde and retrograde tracing ; GABA immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The olivary pretectal nucleus is a primary visual centre, involved in the pupillary light reflex. In the present study an ultrastructural analysis was made of the olivary pretectal nucleus by means of separate, anterograde and retrograde tracing techniques and immunohistochemistry of gamma-aminobutyric acid. Large-projection neurons and two types of gamma-aminobutyric acid-immunoreactive (GABA-ir) neurons are observed in the olivary pretectal nucleus. The primary dendrites of the projection neurons have a dichotomous appearance, the secondary dendrites a multipolar appearance. At the ultrastructural level the projection neurons have well-developed Golgi fields, abundant rough endoplasmic reticulum and the nucleus is always heavily indented. Numerous small GABA-ir neurons and a few medium-sized GABA-ir neurons are found. The small GABA-ir neurons contain a few stacks of rough endoplasmic reticulum and the nucleus is oval-shaped. The medium-sized GABA-ir neurons have well-developed Golgi fields, a moderate number of rough endoplasmic reticulum stacks and an indented nucleus. GABA-positive dendritic profiles containing vesicles also are observed. In the neuropil of the olivary pretectal nucleus, retinal terminals are found that contain round clear vesicles and electron-lucent mitochondria. They make asymmetric synaptic contacts (Gray type I) with dendritic profiles and with profiles containing vesicles. Terminals originating from the contralateral olivary pretectal nucleus exhibit small, round clear vesicles, electron-dense mitochondria and make asymmetric synaptic contacts (Gray type I) mainly with dendritic profiles. Two types of GABA-ir terminals were found. One type is incorporated in glomerulus-like arrangements, whereas the other type is not. GABA-ir terminals contain pleomorphic vesicles, electron-dense mitochondria and make symmetric synaptic contacts (Gray type II). Retinal terminals, terminals originating from the contralateral olivary pretectal nucleus and GABA-ir terminals are organized in glomerulus-like structures, in which dendrites of the large projection neurons form the central elements. Triadic arrangements are observed in these structures; a retinal terminal contacts a dendrite and a GABA-ir terminal and the GABA-ir terminal also contacts the dendrite. The complexity of the synaptic organization and the abundancy of inhibitory elements in the olivary pretectal nucleus suggest that the olivary pretectal nucleus is strongly involved in processing visual information in the pupillary light reflex arc.
    Materialart: Digitale Medien
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 117-123 
    ISSN: 1432-1106
    Schlagwort(e): Key words Muscle contraction ; Electrical stimulation ; Motor unit recruitment ; Spike-triggered averaging ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The recruitment order of motor units (MU) was compared during voluntary and electrically induced contractions. With the use of spike-triggered averaging, a total of 302 MUs with recruitment thresholds ranging from 1% to 88% of maximal voluntary contraction were recorded in the human tibialis anterior muscle in five subjects. The mean (±SD) MU force was 98.3±93.3 mN (mean torque 16.8±15.9 mNm) and the mean contraction time (CT) 46.2±12.7 ms. The correlation coefficients (r) between MU twitch force and CT versus the recruitment threshold in voluntary contractions were +0.68 and –0.38 (P〈0.001), respectively. In voluntary contractions, MUs were recruited in order of increasing size except for only 6% of the cases; whereas, during transcutaneous electrical stimulation (ES) at the muscle motor point, MU pairs showed a reversal of recruitment order in 28% and 35% of the observations, respectively, when the pulse durations were 1.0 ms or 0.1 ms. This recruitment reversal during ES was not related to the magnitude of the difference in voluntary recruitment thresholds between MUs. It is concluded that if the reversal of MU recruitment observed during ES is biophysically controlled by differences in their nerve axon input impedance, in percutaneous stimulation at the motor point, other factors such as the size and the morphological organisation of the axonal branches can also influence the order of activation.
    Materialart: Digitale Medien
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 130-137 
    ISSN: 1432-1106
    Schlagwort(e): Key words Motor control ; Somatosensory system ; Motor timing ; Arm kinematics ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The role of tactile information of the hand in the control of reaching to grasp movements was investigated. The kinematics of both reaching (or transport) and grasp components were studied in healthy subjects in two experimental conditions. In one condition (control condition) subjects were required to reach and grasp an object that could have two sizes and that could be located at two distances from the viewer. In the other condition (anaesthesia condition) the same movements were executed, but anaesthesia was provided to the subjects’ fingertips. In both conditions vision of the hand was prevented during movement. Anaesthesia affected mainly the kinematics of the first phase of grasping, that is, the finger-opening phase. This phase was lengthened and maximal finger aperture increased. In contrast, the duration of the successive phase (finger-closure) was poorly modified. The reaching component was also impaired by anaesthesia. Although the total extent of hand path and the spatial relations between the finger aperture and closure phases did not change between the two conditions, hand path variability increased. This occurred during transport deceleration phase and after the increase in variability of finger path. In addition, the whole movement was slowed down. The results of the present experiment suggest that tactile signals at the beginning and at the end of movement can be used to compute grasp time and to optimise grasp temporal parameters. Alternatively, signals from tactile receptors can be involved in encoding the position sense of the fingers. When this input is lacking, the control of grasp and in particular that of finger-opening phase can be impaired. Finally, the effect of the grasp impairment on the reaching component supports the notion that the coordination between reaching and grasping involves the whole temporal course of the two components.
    Materialart: Digitale Medien
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  • 59
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 163-169 
    ISSN: 1432-1106
    Schlagwort(e): Key words Muscle receptors ; Joint receptors ; Cutaneous mechanoreceptors ; Plantar pressure ; Leg EMG signals ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The purpose of this study was to investigate the possible pathways in the somatosensory system that relate to the postural reflexes in the leg muscles during a sudden, toes-up platform rotation. The inputs to the cutaneous mechanoreceptors in the sole of the foot as well as to the joint receptors in the ankle joint were modulated by standing on different supporting surfaces and by immobilizing the ankle joints; and three leg muscle responses (characterized by short latency, medium latency, and long latency) to the platform movement were recorded in 15 healthy young subjects. It was found that: (1) the short latency was not affected by the changes in either plantar pressure or ankle joint movement; (2) the medium latency was regulated by the plantar pressures under the foot, as sensed by the cutaneous mechanoreceptors in the sole of the foot, and by the ankle joint movement, as perceived by the joint receptors in the ankle joint; (3) the long latency was also related to the ankle joint movement, but this relation seems to be modulated by the plantar pressures under the foot; and (4) both medium and long latencies were well correlated with the time derivative of the pressure difference between the forefoot and the rear foot regions (r=0.7), as well as with the static pressure in the antagonist foot region (r〉0.6).
    Materialart: Digitale Medien
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 170-183 
    ISSN: 1432-1106
    Schlagwort(e): Key words Visually guided reaching ; PET ; MRI ; Posterior parietal cortex ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Positron emission tomography (PET) was used to identify the brain areas involved in visually guided reaching by measuring regional cerebral blood flow (rCBF) in six normal volunteers while they were fixating centrally and reaching with the left or right arm to targets presented in either the right or the left visual field. The PET images were registered with magnetic resonance images from each subject so that increases in rCBF could be localized with anatomical precision in individual subjects. Increased neural activity was examined in relation to the hand used to reach, irrespective of field of reach (hand effect), and the effects of target field of reach, irrespective of hand used (field effect). A separate analysis on intersubject, averaged PET data was also performed. A comparison of the results of the two analyses showed close correspondence in the areas of activation that were identified. We did not find a strict segregation of regions associated exclusively with either hand or field. Overall, significant rCBF increases in the hand and field conditions occurred bilaterally in the supplementary motor area, premotor cortex, cuneus, lingual gyrus, superior temporal cortex, insular cortex, thalamus, and putamen. Primary motor cortex, postcentral gyrus, and the superior parietal lobule (intraparietal sulcus) showed predominantly a contralateral hand effect, whereas the inferior parietal lobule showed this effect for the left hand only. Greater contralateral responses for the right hand were observed in the secondary motor areas. Only the anterior and posterior cingulate cortices exhibited strong ipsilateral hand effects. Field of reach was more commonly associated with bilateral patterns of activation in the areas with contralateral or ipsilateral hand effects. These results suggest that the visual and motor components of reaching may have a different functional organization and that many brain regions represent both limb of reach and field of reach. However, since posterior parietal cortex is connected with all of these regions, we suggest that it plays a crucial role in the integration of limb and field coordinates.
    Materialart: Digitale Medien
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 304-320 
    ISSN: 1432-1106
    Schlagwort(e): Key words Eccentric rotation ; Otolith organs ; Semicircular canals ; Vergence ; Vestibulo-ocular reflex ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We employed binocular magnetic search coils to study the vestibulo-ocular reflex (VOR) and visually enhanced vestibulo-ocular reflex (VVOR) of 15 human subjects undergoing passive, whole-body rotations about a vertical (yaw) axis delivered as a series of pseudorandom transients and sinusoidal oscillations at frequencies from 0.8 to 2.0 Hz. Rotations were about a series of five axes ranging from 20 cm posterior to the eyes to 10 cm anterior to the eyes. Subjects were asked to regard visible or remembered targets 10 cm, 25 cm, and 600 cm distant from the right eye. During sinusoidal rotations, the gain and phase of the VOR and VVOR were found to be highly dependent on target distance and eccentricity of the rotational axis. For axes midway between or anterior to the eyes, sinusoidal gain decreased progressively with increasing target proximity, while, for axes posterior to the otolith organs, gain increased progressively with target proximity. These effects were large and highly significant. When targets were remote, rotational axis eccentricity nevertheless had a small but significant effect on sinusoidal gain. For sinusoidal rotational axes midway between or anterior to the eyes, a phase lead was present that increased with rotational frequency, while for axes posterior to the otolith organs phase lag increased with rotational frequency. Transient trials were analyzed during the first 25 ms and from 25 to 80 ms after the onset of the head rotation. During the initial 25 ms of transient head rotations, VOR and VVOR gains were not significantly influenced by rotational eccentricity or target distance. Later in the transient responses, 25–80 ms from movement onset, both target distance and eccentricity significantly influenced gain in a manner similar to the behavior during sinusoidal rotation. Vergence angle generally remained near the theoretically ideal value during illuminated test conditions (VVOR), while in darkness vergence often varied modestly from the ideal value. Regression analysis of instantaneous VOR gain as a function of vergence demonstrated only a weak correlation, indicating that instantaneous gain is not likely to be directly dependent on vergence. A model was proposed in which linear acceleration as sensed by the otoliths is scaled by target distance and summed with angular acceleration as sensed by the semicircular canals to control eye movements. The model was fit to the sinusoidal VOR data collected in darkness and was found to describe the major trends observed in the data. The results of the model suggest that a linear interaction exists between the canal and otolithic inputs to the VOR.
    Materialart: Digitale Medien
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 25-34 
    ISSN: 1432-1106
    Schlagwort(e): Key words Reaction time ; Saccadic latency ; Saccadic eye movement ; Ocular motor system ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Recent neurophysiological studies of the saccadic ocular motor system have lent support to the hypothesis that this system uses a motor error signal in retinotopic coordinates to direct saccades to both visual and auditory targets. With visual targets, the coordinates of the sensory and motor error signals will be identical unless the eyes move between the time of target presentation and the time of saccade onset. However, targets from other modalities must undergo different sensory-motor transformations to access the same motor error map. Because auditory targets are initially localized in head-centered coordinates, analyzing the metrics of saccades from different starting positions allows a determination of whether the coordinates of the motor signals are those of the sensory system. We studied six human subjects who made saccades to visual or auditory targets from a central fixation point or from one at 10° to the right or left of the midline of the head. Although the latencies of saccades to visual targets increased as stimulus eccentricity increased, the latencies of saccades to auditory targets decreased as stimulus eccentricity increased. The longest auditory latencies were for the smallest values of motor error (the difference between target position and fixation eye position) or desired saccade size, regardless of the position of the auditory target relative to the head or the amplitude of the executed saccade. Similarly, differences in initial eye position did not affect the accuracy of saccades of the same desired size. When saccadic error was plotted as a function of motor error, the curves obtained at the different fixation positions overlapped completely. Thus, saccadic programs in the central nervous system compensated for eye position regardless of the modality of the saccade target, supporting the hypothesis that the saccadic ocular motor system uses motor error signals to direct saccades to auditory targets.
    Materialart: Digitale Medien
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 377-383 
    ISSN: 1432-1106
    Schlagwort(e): Key words Action potential shape ; Concentric needle electrode ; Microneurography ; Myelinated fibres ; Single-unit recording ; Peripheral nerve ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Using standardised concentric needle electrodes 170 single units were recorded from myelinated cutaneous afferents in the human median or ulnar nerves. The unitary waveforms were of four types: single-peaked monophasic potentials (type I), double-peaked monophasic potentials (type II), biphasic potentials (type III) and triphasic potentials (type IV). Type II and IV occurred more frequently than the other types. Units of different functional classes had similar waveforms and there was no specific type of waveform distribution in any particular unit category. In some recording situations there were changes in unitary waveforms from one type to another. There was a tendency for the complex type IV, type III and type II waveforms to change to the simple type I. Adjustment of the electrode often provoked such waveform changes. The waveform profiles and waveform changes observed during recordings with concentric needles were significantly different from those encountered with conventional tungsten electrodes, which might be due to differences in recording properties between the two electrodes. Possible neural mechanisms underlying the observed waveforms and waveform transitions are discussed. In particular, our data suggest that concentric needle electrodes record single-unit activity from myelinated fibres extracellularly.
    Materialart: Digitale Medien
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  • 64
    ISSN: 1432-1106
    Schlagwort(e): Key words Fascia dentata ; Mossy cells ; Interneurons ; Lucifer yellow ; Phaseolus vulgaris leucoagglutinin ; Septohippocampal projection ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Mossy cells in the hilus of the rat dentate gyrus are the main cells of origin of the dentate commissural and associational projections. They project along the septotemporal axis of the dentate gyrus and may thus influence the hippocampal signal flow in a longitudinal direction. To analyze the septal innervation of these hilar neurons, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHAL) was used in combination with intracellular labeling of mossy cells (Lucifer yellow). Anterogradely labeled septal fibers impinge on proximal and distal dendrites of hilar mossy cells but spare the cell body. In contrast, numerous aspiny hilar neurons, presumably GABAergic interneurons, receive a septal innervation on their somata and proximal primary dendrites. These data demonstrate that septal fibers show a specificity for the dendritic segments of hilar mossy cells. Since mossy cells project predominantly to adjacent hippocampal lamellae, the activity of adjacent portions of the dentate gyrus may be influenced by the septal input onto these neurons.
    Materialart: Digitale Medien
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 61-70 
    ISSN: 1432-1106
    Schlagwort(e): Key words First-and second-order motion ; Motion detection ; Perception ; Smooth-pursuit eye movements ; Compensating saccades ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The perception of the displacement of luminance-defined contours (i.e., first-order motion) is an important and well-examined function of the visual system. It can be explained, for example, by the operation of elementary motion detectors (EMDs), which cross-correlate the spatiotemporal luminance distribution. More recent studies using second-order motion stimuli, i.e., shifts of the distribution of features such as contrast, texture, flicker, or motion, extended classic concepts of motion perception by including nonlinear or hierarchical processing in the EMD. Smooth-pursuit eye movements can be used as a direct behavioral probe for motion processing. The ability of the visual system to extract motion signals from the spatiotemporal changes of the retinal image can be addressed by analyzing the elicited eye movements. We measured the eye movement response to moving objects defined by two different types of first-order motion and two different types of second-order motion. Our results clearly showed that the direction of smooth-pursuit eye movements was always determined by the direction of object motion. In particular, in the case of second-order motion stimuli, smooth-pursuit did not follow the retinal image motion. The latency of the initial saccades during pursuit of second-order stimuli was slightly but significantly increased, compared with the latency of saccades elicited by first-order motion. The processing of second-order motion in the peripheral visual field was less exact than the processing of first-order motion in the peripheral field. Steady state smooth-pursuit eye speed did not reflect the velocity of second-order motion as precisely as that of first-order motion, and the resulting retinal error was compensated by saccades. Interestingly, for slow second-order stimuli we observed that the eye could move faster than the target, leading to small, corrective saccades in the opposite direction to the ongoing smooth-pursuit eye movement. We conclude from our results that both visual perception and the control of smooth-pursuit eye movements have access to processing mechanisms extracting first- and second-order motion.
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 531-540 
    ISSN: 1432-1106
    Schlagwort(e): Key words Smooth pursuit ; Steady state pursuit ; Pursuit initiation ; Textured background ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We investigated the effects of stationary and moving textured backgrounds on the initiation and steady state of ocular pursuit using horizontally moving targets. We found that the initial eye acceleration was slightly reduced when a stationary textured background was employed, as compared to experiments with a homogeneous background. When a moving textured background was introduced, the initial eye acceleration was significantly larger when the target and the background moved in opposite directions than when the target and the background moved in the same direction. The use of stationary and moving textured backgrounds resulted in comparable effects on the initial eye acceleration when they were presented either as a large field or as a narrow, horizontal small field, only covering the trajectory of the target. Moreover, small-field stationary backgrounds slightly reduced the eye velocity during steady state pursuit. A small-field background moving in the opposite direction to the target distinctly reduced eye velocity, while a target and a background moving in the same direction sometimes even improved pursuit performance, when compared with a homogeneous background. The influences of small-field textured backgrounds on steady state pursuit were comparable with those of large-field backgrounds in both stationary and moving conditions.
    Materialart: Digitale Medien
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  • 67
    ISSN: 1432-1106
    Schlagwort(e): Key words Anionic surfactants ; Sodium dodecyl sulphate ; Blood-brain barrier ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvascolature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 µg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]α-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, K i, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.
    Materialart: Digitale Medien
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 3-9 
    ISSN: 1432-1106
    Schlagwort(e): Key words Joint nociceptors ; Arthritis ; Articular pain ; Perireceptor events ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Hyaluronan (sodium hyaluronate) is a glycosaminoglycan that is present in all joint tissues. Painful arthritic joints have been characterized by hyaluronan of reduced elastoviscosity. The purpose of this investigation was to determine whether hyaluronan has an influence on joint nociceptor sensitivity and whether restoration of elastoviscosity would decrease nerve responses from nociceptive afferent fibers in arthritic joints. Nerve impulse activity was recorded from nociceptive afferent fibers of the medial articular nerve in anesthetized cats. An acute experimental arthritis was produced by intra-articular injection of kaolin and carrageenan. This caused, within 3 h, the development of ongoing nerve activity and enhancement of nerve impulse responses to passive movements in the normal range of the joint. Intra-articular injection of an elastoviscous solution of hylan, a hyaluronan derivative, significantly reduced both the ongoing activity and the movement-evoked responses in 1–2 h. This effect was not obtained when a nonelastoviscous solution of hylan was injected into the inflamed joint. The results indicate that intra-articularly injected elastoviscous solutions of hylan reduced nociceptive activity in inflamed joints through an elastoviscous, rheological effect on nociceptive afferent fibers through the intercellular matrix in which these fibers are embedded.
    Materialart: Digitale Medien
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 97-103 
    ISSN: 1432-1106
    Schlagwort(e): Key words Chronic constriction injury ; Infraorbital nerve ; Painful trigeminal neuropathy ; Heat-hyperalgesia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Secondary trigeminal neuralgia (STN) follows an injury to the trigeminal nerve or one of its branches. Although rare, this condition results in great suffering and it is notoriously difficult to treat. The experimental analysis of painful neuropathy due to damage to the innervation of the limbs (e.g., the sciatic nerve) has progressed rapidly in recent years, but very few reports have appeared concerning experimental neuropathy in the trigemenial region. We report here an experimental rat model of trigeminal neuropathic pain produced by a chronic constriction injury to the infraorbital nerve (CCI-ION), and on a method that detects heat-evoked pain-related behavior. Rats with the CCI-ION have clear signs of heat-hyperalgesia when stimulated on the snout (the vibrissal pad). The hyperalgesia is seen both ipsi- and contralateral to the side of nerve injury, but is significantly more severe ipsilaterally, and lasts about 12 days.
    Materialart: Digitale Medien
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 469-478 
    ISSN: 1432-1106
    Schlagwort(e): Key words Reaching movements ; Direction ; Extent ; Amplitude ; Variable errors ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Invariant patterns in the distribution of the endpoints of reaching movements have been used to suggest that two important movement parameters of reaching movements, direction and extent, are planned by two independent processing channels. This study examined this hypothesis by testing the effect of task conditions on variable errors of direction and extent of reaching movements. Subjects made reaching movements to 25 target locations in a horizontal workspace, in two main task conditions. In task 1, subjects looked directly at the target location on the horizontal workspace before closing their eyes and pointing to it. In task 2, arm movements were made to the same target locations in the same horizontal workspace, but target location was displayed on a vertical screen in front of the subjects. For both tasks, variable errors of movement extent (on-axis error) were greater than for movement direction (off-axis error). As a result, the spatial distributions of endpoints about a given target usually formed an ellipse, with the principal axis oriented in the mean movement direction. Also, both on- and off-axis errors increased with movement amplitude. However, the magnitude of errors, especially on-axis errors, scaled differently with movement amplitude in the two task conditions. This suggests that variable errors of direction and extent can be modified independently by changing the nature of the sensorimotor transformations required to plan the movements. This finding is further evidence that the direction and extent of reaching movements appear to be controlled independently by the motor system.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 520-530 
    ISSN: 1432-1106
    Schlagwort(e): Key words Hippocampus ; Learning ; Memory ; Recovery ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The monosialoganglioside GM1 is a compound with neurotrophic properties found to foster functional recovery in various paradigms of brain damage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated. Fourteen days later, half the lesioned rats were subjected to intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours after lesion surgery and over a 2-month period, half the rats of each surgical treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half being injected with saline as a control. All rats were subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning performances in both an uninterrupted and an interrupted radial maze testing procedure. In all rats with surviving grafts, the grafts had provided the hippocampus with a new and dense organotypic acetylcholinesterase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ significantly from those of their respective lesion-only counterparts. However, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated counterparts: they used more efficient visit patterns under the uninterrupted testing conditions and made fewer errors under the interrupted ones. The results suggest that GM1 treatment or intrahippocampal grafts used separately do not attenuate the lesion-induced behavioral deficits measured in this experiment. However, when GM1 treatment and grafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 115 (1997), S. 552-556 
    ISSN: 1432-1106
    Schlagwort(e): Key words Eating action ; Motor control ; Grasp ; Motor plan ; Neurophysiology ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The kinematic characteristics of the eating action in humans were assessed. Ten subjects were asked to bring to the mouth pieces of cheese of different sizes (0.7 cm and 2 cm). The pattern of mouth aperture with respect to the size of the food was similar to that found for grasping differently sized objects with the hand. Mouth aperture was appropriately scaled and the time of maximum aperture was reached earlier for the smaller than for the larger piece of cheese. The deceleration phase of the arm was prolonged when the small piece of cheese had to be brought to the mouth with respect to when the large piece of cheese had to be brought to the mouth. Temporal coupling between the time of maximum peak deceleration and the maximum mouth aperture was found in seven of the ten subjects. Taken together these preliminary results suggest that coordinated actions are subserved by the use of a common coordinating schema independently from the effectors involved.
    Materialart: Digitale Medien
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 20-28 
    ISSN: 1432-1106
    Schlagwort(e): Key words Reflex and voluntary control of movement ; Shortening and lengthening contractions ; Long-latency reflex ; Elbow ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Stretch reflex responses in three elbow flexor muscles – the brachioradialis and the short and long heads of the biceps brachii – were studied during different motor tasks. The motor tasks were iso-velocity (8 deg/s) elbow flexion movements in which the muscles performed shortening or lengthening contractions, or were isometric contractions. Care was taken to maintain constant background electromyographic (EMG) activity in the brachoradialis muscle at a 50-deg elbow angle across the tasks by changing the magnitude of the initial load. During each task, mechanical perturbations (duration 170 ms) were applied at pseudorandom intervals when the elbow angle was 50 deg. The magnitude of the perturbation was varied across tasks in order to induce an elbow extension velocity of 80 deg/s over the first 50 ms after the onset of perturbation. The stretch reflex EMG responses in all muscles varied across the three tasks, despite a constant EMG level and similar perturbation-induced angular velocity in the direction of elbow extension. In particular, both the short- and long-latency reflex EMG components were reduced during the lengthening contractions. Further, the task-dependent variations in the early (M2) and the late (M3) components of the long-latency reflex were different, i.e., the magnitude of M3 was considerably enhanced during the shortening task as compared with that of M2. These findings suggest that central modification was responsible for the task-dependent modulation of late EMG responses.
    Materialart: Digitale Medien
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  • 74
    ISSN: 1432-1106
    Schlagwort(e): Key words Amino acid immunocytochemistry ; Axon collateralization ; Thalamus ; Fluorescent tracers ; Limbic system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Small, stereotaxically guided injections of true blue (TB) were made into the retrosplenial granular cortex (RSg) and of diamidino yellow (DY) into the dorsal portion of the rostral pole of the thalamic reticular nucleus (TRN) in 16 adult rats to determine whether axons projecting from the anterior thalamic nuclear complex (ATN) to the TRN are branches of axons also projecting to the RSg. Following injections of the fluorescent dyes, serial coronal sections of the brain revealed single retrogradely labelled, and large numbers of double retrogradely labelled neuronal cell bodies in the ipsilateral anteroventral and anterodorsal nuclei and smaller numbers in the anteromedial nucleus of the ATN complex. In a se- cond series of six adult rats with similar double injections of TB and DY, two sections in three were immunoreacted, one with antiserum against glutamate and one with antiserum against aspartate, using indirect immunofluorescence with rhodamine to detect reactive cells. The great majority of both single and double retrogradely labelled cell bodies were also immunoreactive for aspartate or glutamate. In addition, a moderate to small number of non-immunolabelled neurons projecting to the TRN and/or to the RSg were also found in all three nuclei of the ATN complex. These results are compatible with the possibility that large numbers of neurons in the ATN send axonal branches to both the RSg and the TRN, and that many such neurons use glutamate and/or aspartate as transmitters. The findings also suggest that the projections from the ATN might be heterogeneous with respect to transmitter phenotype.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 324-340 
    ISSN: 1432-1106
    Schlagwort(e): Key words Trigeminal nerve ; Mechanoreceptors ; Cutaneous sensory nerve ending ; Perivascular innervation ; Vibrissae ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  It is well established that sensory perception becomes impaired with advancing age and that, in parallel, dystrophy and degeneration of axons occur in sensory pathways. In this study, the impact of aging was examined in the mystacial pad, which receives a large variety of sensory nerve endings organized in a highly predictable pattern. Mystacial pad specimens from aged (30 months old) and young adult (2–3 months old) female Sprague-Dawley rats were processed, in parallel, for immunohistochemical analyses with antibodies against human neuronal cytoplasmic protein (protein gene product 9.5), transmitter enzymes, and several neuropeptides. Several changes in cutaneous innervation including both degenerative and regenerative processes were evident in the aged rat: (1) the Merkel endings and lanceolate endings that emanate from large-caliber afferents in the whisker follicles were reduced and showed signs of degeneration. Furthermore, a reduction of piloneural complexes at the intervibrissal hairs were evident, but only in aged rats that showed more severe behavioral sensorimotor disturbances. In contrast, Ruffini endings as well as mechanoreceptors emanating from medium-caliber axons, i.e., transverse lanceolate and reticular endings, appeared normal. (2) A reduction was evident among two sets of unmyelinated epidermal endings; however, the epidermal innervation affiliated with the intervibrissal hairs appeared normal in the aged rat. (3) A loss of sympathetic neuropeptide tyrosine (NPY) or tyrosine hydroxylase-immunoreactive (IR) and somatosensory Calcitonin gene-related peptide (CGRP)-IR perivascular axons was paralleled by an increase in presumed parasympathetic NPY/CGRP-IR axons. (4) Two “novel” networks of fine-caliber axons were observed in the outer and inner root sheaths of the whisker follicles in the aged rat. (5) NPY was present in a population of small-caliber, somatosensory CGRP-IR axons in the aged rat. This may represent a de novo synthesis, since, normally, NPY-like immunoreactivity is not observed in this set of axons. Our results suggest that the sensory impairments occurring with advancing age are part of a peripheral process instigated by changes in nerve-target interactions and/or incapacitation of the neuronal machinery to sustain the axonal integrity.
    Materialart: Digitale Medien
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  • 76
    ISSN: 1432-1106
    Schlagwort(e): Key words “Central pain” ; Picrotoxin ; Epilepsy ; Acetylcholine ; Cortex ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In this study, we examined the modulation by acetylcholine of electrocorticographical (ECoG) ictal events and spontaneous pain-like behaviors following cortical application of the GABAA antagonist picrotoxin in the awake rat. Distilled water as vehicle, the cholinomimetic substance eserine, and the general muscarinic antagonist atropine were microinjected 10 min before the second microinjection of 2 μg picrotoxin into the hind paw region of the somatomotor cortex (SmI). Under these conditions, we observed that eserine (physostigmine, 1 μg, 10 μg, and 20 μg) did not consistently modify the number of the picrotoxin-induced ECoG spikes and bursts, but instead produced a massive enhancement of the number of hind paw licks compared with vehicle at 10 μg and, to a lesser extent, the number of the stereotyped “turn-in” and “neglected” paws following picrotoxin. In contrast, atropine (l μg, 10 μg, and 20 μg) increased the number of the picrotoxin-induced spikes and bursts at 10 μg and, at all doses, decreased the number of the picrotoxin-induced pain-like symptoms. Statistically significant changes for the number of paw lifts, licks, and “turn-in” paws were observed only with 10 μg. These results tend to show that epilepsy and pain are not strictly related to each other and also emphasize the cortex as a target for interactions between GABA and acetylcholine relative to “central” pain.
    Materialart: Digitale Medien
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 80-86 
    ISSN: 1432-1106
    Schlagwort(e): Key words Hippocampus ; Commissural fibers ; Reactive sprouting ; Synaptogenesis ; Synaptophysin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Expression of the synaptic vesicle protein synaptophysin was studied in lesion-induced sprouting neurons of the contralateral entorhinal cortex and in the contralateral dentate gyrus using immunocytochemistry at the light- and electron-microscopic level. Perikaryal immunoreactivity for synaptophysin was found between 8 and 10 days postlesion. Light microscopy revealed that synaptophysin immunostaining was present in almost all neurons of layers II and III of the contralateral medial entorhinal cortex. These neurons give rise to the sprouting, crossed temporodentate pathway. In addition, some hilar neurons of the contralateral dentate gyrus, which are the parent cells of sprouting commissural fibers, were immunostained for synaptophysin. Transient immunostaining for synaptophysin was observed within cell bodies and dendrites. Additionally, the cell bodies were outlined by immunoreactive puncta, identified by electron microscopy as nerve terminals. Our results revealed that sprouting neurons express the major synaptic vesicle protein synaptophysin during reactive synaptogenesis in a pattern that reflects biosynthesis and sorting of this protein as seen in developing neurons during synapse formation.
    Materialart: Digitale Medien
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 87-96 
    ISSN: 1432-1106
    Schlagwort(e): Key words Magnetic stimulation ; Resetting ; Motor cortex ; Rhythmical movement ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We studied the effects of changes in loading torque on the effectiveness of magnetic cortical stimulation in evoking phase resetting of voluntary wrist movement. Nine normal subjects were studied (five on two occasions), while making rhythmical movements of the right wrist, at their preferred rate, against extension torque loads of 0.35 Nm, 0.26 Nm and 0.18 Nm, flexion torque loads of 0.09 Nm and 0.18 Nm and without external load. The position records of individual trials were used to measure the effectiveness of resetting (resetting index: the slope of the phase-response curve) and the ”null phase”, the phase to which the trials were being reset. The loading torque had a strong influence upon both the resetting index and the null phase, generated by a constant intensity of cortical stimulation such that the largest resetting indices were obtained for movements made against the largest extension torque load (mean resetting index 0.72). The degree of resetting and null phase were related to the mean amplitude and direction of the first poststimulus position peak, which in turn was largely determined by the twitch induced by the cortical shock. The timings of the averaged poststimulus position peaks following the first were simple multiples of the prestimulus movement period. Our results indicate that loading conditions profoundly influence the effectiveness of magnetic cortical stimulation in resetting a voluntary movement and that these effects appear to be largely explicable by the changes in the muscle twitch evoked by the stimulus with the different loads. We suggest that the magnetic shock is therefore unlikely to reset voluntary movement by an action directly upon the motor programme. We propose that the main method by which magnetic cortical stimulation resets repetitive wrist movement is indirect: normal generation of repetitive wrist flexion and extension is disrupted by the cortical shock, following which afferent information related to the twitch induced is able to reset the movement.
    Materialart: Digitale Medien
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 117 (1997), S. 457-464 
    ISSN: 1432-1106
    Schlagwort(e): Key words Prehension ; Spatiotemporal variability ; Motor control ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Human prehension movements have been studied with regard to the parallel processing of motor control and sensorimotor coordination. Temporal aspects of the movement (e.g., onset time and duration) have been studied extensively, while spatial aspects have not been studied systematically. Thus, the purpose of this study was to examine spatiotemporal variability of the transport (wrist trajectory) and grasp (grip aperture between the index finger and the thumb) components. In this experiment, the extrinsic (e.g., distance) and intrinsic object properties (e.g., object size) were manipulated. Subjects were required to pick up an aluminum cylinder as quickly and accurately as possible using the index finger and the thumb. It was found that object size significantly affected both transport and grasp components. Distance mainly affected the transport component. These kinematic results were consistent with the findings of earlier studies. Furthermore, the distribution of mean within-subject variability across normalized movement time for the transport component was not the same as that of the grasp component, suggesting that the different motor control processes exist. The peak amplitudes in variability of the wrist trajectory and the grip aperture were obtained at similar points throughout movement time. Furthermore, the peak of wrist variability depended on distance not object size, while that of aperture variability depended on both distance and object size. These results strongly support the hypothesis that the grasp component is adjusted using dynamic information provided from the transport component as the wrist moves toward the object. We also found that wrist variability converged to the target point, while aperture variability was biphasic: it converged, at least, around the point of maximum aperture in the first phase and then remained constant in the second phase. This result suggests that the two components are under different control processes. We hypothesize that the transport component can be modeled as a single feedforward system, while the grasp component can be divided into two separate mechanisms.
    Materialart: Digitale Medien
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  • 80
    ISSN: 1432-1106
    Schlagwort(e): Key words Locomotor recovery ; Neural transplantation ; Fictive locomotion ; Serotonin ; 6-Hydroxydopamine ; Zimelidine ; Rat ; Spinal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Locomotor movements are programmed in a specialised neuronal network that is localised in the central nervous system and referred to as the central pattern generator (CPG) for locomotion. This CPG can be activated by pharmacological agents such as monoamines. The aim of the present study was to try to activate the CPGs by using cells that are supposed to release serotonin locally. Adult chronic spinal rats were injected with embryonic brainstem neurons within the spinal cord under a thoracic transection. This procedure resulted in a monoaminergic reinnervation of the lumbar enlargement. With the help of a specific neurotoxin for noradrenergic neurons (6-hydroxydopamine), it was possible to isolate the serotonergic system. After such transplantation of monoaminergic neurons and even with serotonergic neurons alone, a bilateral, alternating, rhythmic locomotor-like activity recovered in hindlimbs. Furthermore, this locomotor-like activity was clearly facilitated when the re-uptake of serotonin was blocked by zimelidine. Therefore, we conclude that transplanted embryonic serotonergic neurons are able to activate the CPG for locomotion.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 465-474 
    ISSN: 1432-1106
    Schlagwort(e): Key words Arm movement ; EMG ; Motor learning ; Torque ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Nine young infants were followed longitudinally from 4 to 15 months of age. They performed multijoint reaching movements to a stationary target presented at shoulder height. Time-position data of the hand, shoulder, and elbow were collected using an optoelectronic measurement system. In addition, we recorded electromyographic activity (EMG) from arm extensors and flexors. This paper documents how control problems of proximal torque generation may account for the segmented hand paths seen during early reaching. Our analysis revealed the following results: first, muscular impulse (integral of torque) increased significantly between the ages of 20 (reaching onset) and 64 weeks. That is, as infants got older they produced higher levels of mean muscular flexor torque during reaching. Data were normalized by body weight and movement time, so differences are not explained by anthropometric changes or systematic variations in movement time. Second, while adults produced solely flexor muscle torque to accomplish the task, infants generated flexor and extensor muscle torque at shoulder and elbow throughout a reach. At reaching onset more than half of the trials revealed this latter kinetic profile. Its frequency declined systematically as infants got older. Third, we examined the pattern of muscle coordination in those trials that exhibited elbow extensor muscle torque. We found that during elbow extension coactivation of flexor and extensor muscles was the predominant pattern in 67% of the trials. This pattern was notably absent in comparable adult reaching movements. Fourth, fluctuations in force generation, as measured by the rate of change of total torque (NET) and muscular torque (MUS), were more frequent in early reaching (20–28 weeks) than in the older cohort (52–64 weeks), indicating that muscular torque production became increasingly smoother and task-efficient. Our data demonstrate that young infants have problems in generating smooth profiles of proximal joint torques. One possible reason for this imprecision in infant force control is their inexperience in predicting the magnitude and direction of external forces. That infants learned to consider external forces is documented by their increasing reliance on these forces when performing voluntary elbow extensions. The patterns of muscle coordination underlying active elbow extensions were basically the same as during the prereaching phase, indicating that the formation of functional synergies is based on a basal repertoire of innervation patterns already observable in very early, spontaneous movements.
    Materialart: Digitale Medien
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 113 (1997), S. 520-533 
    ISSN: 1432-1106
    Schlagwort(e): Key words Spinal Ia terminations ; Action potentials ; Baclofen ; Calcium influx ; Cat ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses.
    Materialart: Digitale Medien
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  • 83
    ISSN: 1432-1106
    Schlagwort(e): Key words Forebrain ischemia ; Hyperglycemia ; Hippocampus ; Bioenergetic state ; Cyclosporin A ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A recent study from this laboratory has shown that brief transient ischemia (2 min 30 s) in normo- and hyperglycemic rats leads to moderate neuronal necrosis in CA1 cells of the hippocampus, of equal density in the two groups. However, hyperglycemic animals failed to depolarize during the ischemia, nor did they show a decrease in extracellular calcium concentration. The present study was undertaken to study the metabolic correlates to these unexpected findings. Normoglycemic (plasma glucose ∼6 mM) and hyperglycemic (∼20 mM) rats were subjected to ischemic periods of 1 min and 2 min 15 s (2 min 30 s with freezing delay considered), and their brains were frozen in situ. Samples of dorsal hippocampus were dissected at –22°C and extracted for the measurement of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glucose, glycogen, and lactate. Normoglycemic animals showed rapid depletion of PCr, ATP, glucose, and glycogen, and a rise in lactate content to 10–12 mM·kg–1 during the ischemia. Hyperglycemic animals displayed a more moderate rate of fall of PCr and ATP, with ATP values exceeding 50% of control after 2 min 30 s. Glycogen stores were largely maintained, but degradation of glucose somewhat enhanced the lactic acidosis. The results demonstrate that hyperglycemic rats maintained ATP at levels sufficient to prevent cell depolarization and calcium influx during the ischemic period. However, the metabolic perturbation observed must have been responsible for the delayed neuronal damage. We speculate that lowered ATP, increased inorganic P, and oxidative stress triggered a delayed mitochondrial permeability transition (MPT), which led to delayed neuronal necrosis. This assumption was supported by a second series of experiments in which CA1 damage in hyperglycemic rats was prevented by cyclosporin A, a virtually specific inhibitor of the MPT.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 114 (1997), S. 63-70 
    ISSN: 1432-1106
    Schlagwort(e): Key words Vision ; Locomotion ; Optic Flow Adaptation ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The effect of an optic flow pattern on human locomotion was studied in subjects walking on a self-driven treadmill. During walking an optic flow pattern was presented, which gave subjects the illusion of walking in a tunnel. Visual stimulation was achieved by a closed-loop system in which optic flow and treadmill velocity were automatically adjusted to the intended walking velocity (WV). Subjects were instructed to keep their WV constant. The presented optic flow velocity was sinusoidally varied relative to the WV with a cycle period of 2 min. The independent variable was the relative optic flow (rOF), ranging from −1, i.e., forward flow of equal velocity as the WV, and 3, i.e., backward flow 3 times faster than WV. All subjects were affected by rOF in a similar way. The results showed, firstly, an increase in stride-cycle variability that suggests a larger instability of the walking pattern than in treadmill walking without optic flow; and, secondly, a significant modulating effect of rOF on the self-chosen WV. Backward flow resulted in a decrease, whereas forward flow induced an increase of WV. Within the analyzed range, a linear relationship was found between rOF and WV. Thirdly, WV-related modulations in stride length (SL) and stride frequency (SF) were different from normal walking: whereas in the latter a change in WV is characterized by a stable linear relationship between SL and SF (i.e., an approximately constant SL to SF ratio), optic flow-induced changes in WV are closely related to a modulation of SL (i.e., a change of SL-SF ratio). Fourthly, this effect of rOF diminished by about 45% over the entire walking distance of 800 m. The results suggest that the adjustment of WV is the result of a summation of visual and leg-proprioceptive velocity informations. Visual information about ego-motion leads to an unintentional modulation of WV by affecting specifically the relationship between SL and SF. It is hypothesized that the space-related parameter (SL) is influenced by visually perceived motion information, whereas the temporal parameter (SF) remains stable. The adaptation over the entire walking distance suggests that a shift from visual to leg-proprioceptive control takes place.
    Materialart: Digitale Medien
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  • 85
    ISSN: 1432-1106
    Schlagwort(e): Key words Enkephalin ; GABA ; Basal ganglia ; 6-Hydroxydopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  In Parkinson’s disease the dopaminergic nigrostriatal pathway degenerates, resulting in an imbalance in activity of two pathways of information flow through the basal ganglia. In animal models of the disease, the striatonigral pathway becomes underactive and the striatopallidal pathway becomes overactive. In the present study immunocytochemistry for enkephalin and GABA and anterograde labelling were used to investigate whether morphological plasticity occurs in striatopallidal terminals following unilateral removal of the nigrostriatal dopaminergic pathway. Pallidal terminals were immunostained to reveal enkephalin and examined in the electron microscope (n=399). Immunoreactive synaptic bouton profiles were on average 64% larger on the experimental side 26 days after the lesion. Analysis of their shape revealed that those on the dopamine-depleted side of the brain were more irregular in profile and that their synaptic specialisations were more complex in shape but not significantly different in length. Striatopallidal terminals were also identified by GABA immunocytochemistry combined with anterograde labelling (n=20). Double-labelled boutons were significantly larger in cross-sectional area on the experimental side (57%). Analysis of terminals that were simply labelled by the immunogold method to reveal GABA (n=278) showed no significant differences in size between terminals from the dopamine-depleted and control side. This suggests that a substantial number of GABAergic terminals in the globus pallidus do not belong to the striatopallidal population of terminals. These morphological changes correlate with previous studies suggesting striatopallidal boutons are more active after destruction of dopaminergic input to the neostriatum.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 83-96 
    ISSN: 1432-1106
    Schlagwort(e): Key words Smooth pursuit ; Adaptation ; Peripheral motion signal ; Topography ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The main purpose of the present study was to investigate adaptive properties in human smooth-pursuit eye movements generated by a peripheral moving target. In adaptation trials, a target appeared in the peripheral visual field and immediately moved away at a constant speed, and a subject made a saccade and postsaccadic pursuit responses to track it. The target speed was, however, changed to a higher or lower constant speed (step-ramp-ramp target motion) at the termination of the saccade. This adaptation paradigm induced adaptive modifications in postsaccadic pursuit responses and our results revealed the following properties of the pursuit adaptation system. Topographic modification: Modification of the initial pursuit velocity depends on the position of a moving target. Pursuit gain change: Pursuit velocity is modified not by the addition of a constant bias to the pre-adaptation pursuit velocity, but by a change in the pursuit gain (pursuit velocity/target velocity). Lack of influence on saccade properties: Pursuit adaptation does not change the amplitude and latency of saccades either to a moving target or to a stationary target.
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 122-130 
    ISSN: 1432-1106
    Schlagwort(e): Key words Posture ; Arm movement ; Hand grip force ; Load force ; Anticipation ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The reactive forces and torques associated with moving a hand-held object between two points are potentially destabilising, both for the object’s position in the hand and for body posture. Previous work has demonstrated that there are increases in grip force ahead of arm motion that contribute to object stability in the hand. Other studies have shown that early postural adjustments in the legs and trunk minimise the potential perturbing effects on body posture of rapid voluntary arm movement. This paper documents the concurrent evolution of grip force and postural adjustments in anticipation of dynamic and static loads. Subjects held a manipulandum in precision grasp between thumb and index finger and pulled or pushed either a dynamic or a fixed load horizontally towards or away from the body (the grasp axis was orthogonal to the line of the load force). A force plate measured ground reaction torques, and force transducers in the manipulandum measured the load (tangential) and grip (normal) forces acting on the thumb and finger. In all conditions, increases in grip force and ground reaction torque preceded any detectable rise in load force. Rates of change of grip force and ground reaction torque were correlated, even after partialling out a common dependence on load force rate. Moreover, grip force and ground reaction torque rates at the onset of load force were correlated. These results imply the operation of motor planning processes that include anticipation of the dynamic consequences of voluntary action.
    Materialart: Digitale Medien
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 116 (1997), S. 191-200 
    ISSN: 1432-1106
    Schlagwort(e): Key words Saccade ; Reaction time ; Antisaccade ; Fixation ; Gap effect ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  We investigated the effect of different spatial and temporal parameters on the saccadic reaction times (SRTs) of the antisaccades and on the frequency and the SRTs of erratic prosaccades in five adult human subjects. The subjects were instructed to aim their saccades to the side opposite to where a visual go-stimulus occurred. Parameters under consideration were: the gap duration (between 0 and 600 ms, and an overlap paradigm); the stimulus size (sizes of 0.1°, 0.2°, and 0.4°, using the gap 200-ms paradigm); and the stimulus eccentricity (1°, 2°,4°, 8°, and 12°, with the gap 200-ms paradigm). A decrease in the anti SRTs and an increase in the error rate were observed with medium gap durations (200 ms, 250 ms), while the anti-SRTs were longer and the error rates lower with the shorter values (0 ms, 100 ms, and with the overlap paradigm) and with the long values (600 ms). A slight decrease in the anti-SRTs and an increase in the error frequency occurred with increasing eccentricity; the SRT distributions of the errors resembled closely those of prosaccades in corresponding prosaccade tasks with the same eccentricities. The stimulus size had only modest or no effects at all. Analysis of the distributions of the correction times of the erratic prosaccades showed that the intersaccadic intervals could be very short: in the range of express saccades, with a peak at 100 ms; or in some subjects even shorter, with a peak at 40–50 ms. It is concluded that the performance of antisaccades is influenced by parameters that interact with the fixation and/or attention system of oculomotor control. Parameters supporting a disengagement of fixation at the time of stimulus onset provoke a reduction of the saccadic reaction times not only of prosaccades but also of antisaccades. Moreover, a certain state of disengagement seems to facilitate the occurrence of reflex-like errors.
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  • 89
    ISSN: 1432-1211
    Schlagwort(e): Key words HLA ; Microsatellite loci ; Microsatellite typing ; Human ; MHC
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  The human genome contains a large number of interspersed microsatellite repeats which exhibit a high degree of polymorphism and are inherited in a Mendelian fashion, making them extremely useful genetic markers. Several microsatellites have been described in the HLA region, but allele nomenclature, a set of broadly distributed controls, and typing methods have not been standardized, which has resulted in discrepant microsatellite data between laboratories. In this report we present a detailed protocol for genotyping microsatellites using a semi-automated fluorescence-based method. Twelve microsatellites within or near the major histocompatibility complex (MHC) were typed in the 10th International Histocompatibility Workshop homozygous typing cell lines (HTCs) and alleles were designated based on size. All loci were sequenced in two HTCs providing some information on the level of complexity of the repeat sequence. A comparison of allele size obtained by genotyping versus that obtained by direct sequencing showed minor discrepancies in some cases, but these were not unexpected given the technical differences in the methodologies. Fluorescence-based typing of microsatellites in the MHC described herein is highly efficient, accurate, and reproducible, and will allow comparison of results between laboratories.
    Materialart: Digitale Medien
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    International archives of occupational and environmental health 69 (1997), S. 491-497 
    ISSN: 1432-1246
    Schlagwort(e): Key words Dimethylhippuric acid ; Trimethylbenzene ; Toxicokinetics ; Urine ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The aim of this study was to determine the urinary excretion of dimethylhippuric acids (DMHAs) in humans after experimental chamber exposure to trimethylbenzene (TMB) vapor. The DMHAs have been put forward as suitable biomarkers of exposure to products containing TMBs such as white spirit and petrol. Ten healthy male volunteers were exposed to TMB vapor in an exposure chamber for 2 h at a work load of 50 W. The subjects were exposed on four occasions, to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB, respectively, and to 2 ppm of 1,2,4-TMB. Urine was collected from the onset of exposure until the following morning. All six possible DMHA isomers were analyzed by high-performance liquid chromatography. About 22% of the inhaled amount of 1,2,4-TMB was excreted as DMHAs within 24 h, mainly as 3,4-DMHA. The 24-h recovery of 1,2,3-TMB as DMHAs was 11%. Only 3% of the absorbed amount of 1,3,5-TMB was excreted as 3,5-DMHA. The half-times of the different DMHA isomers ranged from 4 to 16 h. In addition to analysis of DMHAs, the excretion of unconjugated dimethylbenzoic acids in urine was estimated to account for approximately 3% of the dose of all TMBs. In conclusion, the urinary excretion of DMHA isomers may serve as a good indicator of TMB exposure. In this controlled short-term-exposure study the sum of excretion rate of several DMHA isomers reflected exposure more closely than did the excretion rate of any single DMHA.
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  • 91
    ISSN: 1432-1211
    Schlagwort(e): Key words CD4 ; Rat ; LEC ; thid ; Chromosomal mapping
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 92
    ISSN: 1432-1912
    Schlagwort(e): Key words Neocortex ; Cholecystokinin ; Dynorphin ; Amino acids ; Microdialysis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of sulphated cholecystokinin-8 (CCK-8S) on extracellular dynorphin B, aspartate, glutamate and GABA levels in the rat fronto-parietal cortex was investigated with in vivo microdialysis. The peptide was infused through the microdialysis probe trying to mimic local CCK-8S release. Basal levels of dynorphin B were around 20pM, aspartate 100nM, glutamate 600nM and GABA 30nM. CCK-8S (10μM) induced a ≈3-fold increase in extracellular dynorphin B, aspartate and glutamate levels, while GABA levels were only slightly increased. The effect of CCK-8S was restricted to the stimulated neocortex. Systemic pretreatment with the CCKB antagonist, L-365, 260, but not with the CCKA antagonist, L-364, 718, significantly antagonised the effect of CCK-8S on cortical dynorphin B and aspartate release. However, both CCKA and CCKB antagonists inhibited the increase in cortical glutamate levels. Thus, the present results indicate that cortical CCK release exerts a stimulatory modulation on cortical dynorphin B and aspartate release via the CCKB receptor subtype, and on glutamate release via both CCKA and CCKB receptor subtypes. Considering electrophysiological evidence that CCK increases neuronal firing rates in many brain regions, it may be suggested that CCK represents a stimulatory system modulating the function of the neocortex.
    Materialart: Digitale Medien
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 355 (1997), S. 595-600 
    ISSN: 1432-1912
    Schlagwort(e): Key words Morphine ; Nitric oxide ; Apomorphine ; Oxytocin ; Penile erection ; Yawning ; Paraventricular nucleus of the hypothalamus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The possible involvement of nitric oxide in the prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning was investigated by measuring the concentration of NO2- and NO3- in the dialysate obtained with a vertical microdialysis probe implanted in the paraventricular nucleus of the hypothalamus of male rats. Either apomorphine (80 µg/kgs.c.) or oxytocin (30 ng i.c.v.) increased significantly basal NO2- and NO3- concentration in the paraventricular dialysate, penile erection and yawning. Morphine (1, 5 and 10mg/kg i.p.) prevented dose-dependently either apomorphine or oxytocin responses when given 15min before apomorphine or oxytocin. Prevention by morphine of apomorphine and oxytocin responses was abolished by naloxone (3mg/kg i.p.) given 15min before morphine. Morphine prevented apomorphine and oxytocin responses also when given in the lateral ventricles or directly in the paraventricular nucleus. In contrast, the selective agonist of the kappa opioid receptor subtype U-69,593 was found to be ineffective. The present results confirm previous findings showing that morphine acts through µ receptors in the paraventricular nucleus to prevent apomorphine and oxytocin-induced penile erection and yawning and suggest that this morphine effect is mediated by a decreased activity of nitric oxide in the paraventricular nucleus of the hypothalamus.
    Materialart: Digitale Medien
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 355 (1997), S. 689-698 
    ISSN: 1432-1912
    Schlagwort(e): Key words β-adrenoceptors ; β adrenoceptor antagonists ; Celiprolol ; Rat ; Blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Celiprolol is a β-adrenoceptor antagonist which has desirable ancillary properties since it is relatively cardioselective and can exert direct vasodilator and bronchodilator effects. Here agonist and antagonist effects of celiprolol at cardiac β1- and vascular β2-adrenoceptors were determined under in vivo conditions in the rat. All experiments were carried out in catecholamine-depleted, pentobarbital anesthetized and vagotomized rats, placed under artificial respiration. I.v. administrations were madevia the femoral vein. Blood pressure was measured from the cannulated right carotid artery and heart rate was recorded with a cardiotachometer. Celiprolol (10 µg/kg to 1 mg/kg i.v.) produced dose-related increases in heart rate and decreases in mean carotid artery blood pressure which were of longer duration than those mediated by standard agonists of β1-(isoprenaline) or β2-(salbutamol) adrenoceptors respectively. Although the maximal increase in heart rate by celiprolol (110±4 beats/min, n=7) was approximately half that of isoprenaline (198±1 beats/min, n=5), isoprenaline acted at doses 200-fold lower than celiprolol. Betaxolol (0.03-0.3 mg/kg i.v.), a β1-adrenoceptor antagonist, inhibited strongly and with similar potency the tachycardic effects of celiprolol (DR10 = 45 µg/kg i.v.) as well as isoprenaline (DR10 = 45 µg/kg i.v.). On the other hand, the hypotensive effects of celiprolol and salbutamol were antagonized markedly and with similar potency by ICI118,551, a relatively selective β2-adrenoceptor antagonist (DR10 = 15 and 25 µg/kg i.v. respectively). In rats pretreated with celiprolol (0.03 to 0.3 mg/kg i.v.), the heart rate dose-response curves to isoprenaline were shifted to the right of those determined in matched groups of vehicle-pretreated animals. In this respect, celiprolol was half as potent as betaxolol in blocking cardiac β1-adrenoceptors. Furthermore, celiprolol also antagonized the hypotensive effects of salbutamol, but, in this respect, celiprolol was 90-fold less potent than ICI 118,551. In conclusion, these results clearly indicate that celiprolol has the ability of stimulating and blocking not only cardiac β1- but also vascular β2-adrenoceptors. The effects on cardiac β1-adrenoceptors as well as the agonism of β2-adrenoceptors are produced by similar doses of celiprolol. These doses are notably lower than those necessary to block β2-adrenoceptors. Thus, this pharmacological profile, which has also been demonstrated in humans, indicates that celiprolol is a modulator of cardiac β1-adrenoceptors with vascular β2-adrenoceptor agonist properties.
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  • 95
    ISSN: 1432-1912
    Schlagwort(e): Key words γ2-MSH (γ2-melanocyte-stimulating ; hormone) ; Blood pressure ; Heart rate ; Prazosin ; Metoprolol ; SR 49059 ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract γ2-Melanocyte-stimulating hormone (γ2-MSH) and related melanotropins have been shown to have various cardiovascular effects, including acute, short-lasting increases in blood pressure (MAP) and heart rate (HR). γ2-MSH, administered intravenously, dose-dependently increased MAP and HR with an ED50 of approximately 30 nmol/kg and a maximal effect on MAP of approximately 55 mm Hg and on HR of around 70 beats per minute. Intravenous (i.v.) pretreatment with the α1-adrenoceptor antagonist, prazosin, caused the dose-response curve for the effect of γ2-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR. I.v. pretreatment with the β1-adrenoceptor antagonist, metoprolol, had no effect on the dose-response curve for the effect of γ2-MSH on MAP, but it caused the dose-response curve for the effect of the peptide on HR to shift to the right with a decrease in slope. Neither i.v. nor intracerebroventricular (i.c.v.) administration of the vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-response curves for the effects of the peptide on either MAP or HR. The doses of prazosin, metoprolol and SR 49059 were found to be effective in counteracting the effects of agonists for these receptors (phenylephrine, isoprenaline and [Arg8]vasopressin, respectively). Taken together, these results support the postulate that the effects of γ2-MSH are, at least partially, due to an increase in sympathetic outflow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R681-R694), and that this increase leads to increased activation of vascular α1-adrenoceptors and cardiac β1-adrenoceptors. If, as was suggested by these authors, γ2-MSH acts via activation of a central vasopressin system, it is via a vasopressin receptor subtype other than the vasopressin V1A receptor, since i.c.v. administration of a selective vasopressin V1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of γ2-MSH.
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 355 (1997), S. 743-750 
    ISSN: 1432-1912
    Schlagwort(e): Key words Erythromycin ; Potassium channels ; Arrhythmias ; Kv1.5 ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Erythromycin administration has been associated with a prolongation of cardiac repolarization in certain clinical settings. This could be due to blockade of voltage-dependent K+ channels in the human heart. For this reason we examined the effects of erythromycin on a rapidly activating delayed rectifier K+ channel (Kv1.5) cloned from human heart and stably expressed in human embryonic kidney cells. When examined using the whole-cell patch clamp technique, erythromycin (100 μM) blocked Kv1.5 current in a time-dependent manner but required prolonged exposure to do so. However, when we examined Kv1.5 current using inside-out macropatches, erythromycin applied to the cytoplasmic surface rapidly (within 1-2 min) inhibited Kv1.5 current with an IC50 value of 2.6 x 10-5M (1.7 - 3.9 x 10-5M, 95% C.L.). The main effect of erythromycin was to accelerate the rate of Kv1.5 current decay thereby reducing the current at the end of a prolonged voltage-clamp pulse. Erythromycin also blocked Kv1.5 current in both a voltage- and frequency-dependent manner but had little effect on the activation kinetics, deactivation kinetics, or the steady-state inactivation properties of Kv1.5. These data suggest that erythromycin acts as a blocker of an activated state of the Kv1.5 channel and that it may access its binding site from the intracellular face of the channel. This study is the first to examine the effects of erythromycin on a cloned human cardiac K+ channel. It is concluded that erythromycin blocks Kv1.5 at clinically relevant concentrations. Blockade of voltage-dependent K+ channels in the heart could contribute to the alterations in cardiac repolarization that have been observed with erythromycin.
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  • 97
    ISSN: 1432-1912
    Schlagwort(e): Key words N-Methyl-D-aspartate (NMDA) antagonists ; Locomotion ; Stereotypy ; Catalepsy ; Basal ganglia ; Dopamine antagonists ; Dopamine metabolism ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of systemic administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonists dextrorphan (10–40mg/kg, i.p.) and [±]-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (ADCI) (25–70mg/kg, i.p.) on basal ganglia-mediated behaviour and on forebrain dopamine metabolism were investigated in rats. Dextrorphan increased locomotor activity but did not induce stereotyped sniffing. ADCI failed to produce any significant motor stimulant and motor depressant actions. Both dextrorphan and ADCI dose-dependently antagonized catalepsy induced by the D-1 dopamine receptor antagonist SCH 23390 or the D-2 dopamine receptor antagonist haloperidol. Only the highest doses of dextrorphan and ADCI increased dopamine metabolism in the prefrontal cortex and/or in the nucleus accumbens, but not in the dorsal striatum. Our results show that dextrorphan and ADCI produce some of the behavioural effects (antagonism of experimentally induced catalepsy) and neurochemical actions (regionally selective stimulation of dopamine metabolism) that have previously been observed in the prototypical non-competitive NMDA antagonist, dizocilpine. The failure of ADCI to induce hyperlocomotion and stereotypy suggests that anticataleptic doses of ADCI may be devoid of the psychotomimetic actions commonly associated with non-competitive blockade of NMDA receptor function.
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  • 98
    ISSN: 1432-1912
    Schlagwort(e): Key words Daily rhythms ; Heart rate ; Temperature ; Locomotor activity ; Anaesthesia ; Ether ; Ketamine ; Rat ; Telemetry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of this study was to evaluate the effect of anaesthesia (ether or ketamine) on daily rhythms of temperature (T), heart rate (H) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. T, H and A were measured every 10min, in Wistar male rats, and analysed using Cosinor. The mean±SEM days needed, after surgical implantation, to detect a daily rhythm in H, T and A were also assessed. Six rats were anaesthetized for about 50min either by ketamine or ether in a 3 by 3 cross-over design. Mesors, amplitudes and acrophases of T, H and A were calculated three days before (D-3; D-2; D-1), the day of anaesthesia (D0) as well as the three following days (D1; D2; D3). ANOVA was performed in order to detect, firstly a possible effect due to the order of application of anaesthesia, secondly a significant difference between ether or ketamine-induced anaesthesia and finally a modification of the mesors, amplitudes and acrophases of T, H and A, induced by each anaesthesia, for D0, D1, D2 and D3 when compared to D-1. Our results indicate: (1) Alterations of the acrophases, mesors and amplitudes, except for the amplitude of A, of the daily rhythms of T, H and A on D0 of ketamine anaesthesia while regarding ether anaesthesia only amplitude of T and H and acrophase of A were modified on D0. Some of these modifications were still observed on the days following anaesthesia. A significant difference between ether and ketamine-induced anaesthesia was also observed. (2) A non-detection of T, H and A daily rhythms after surgical implantation, which was not observed after injection of either ether or ketamine alone. Almost 10 days were needed to detect a significant daily rhythm for T, H and A. The authors suggest that, the general anaesthetic agent was responsible for a perturbation of the mesors, amplitudes and acrophases of the daily rhythms of H, T and A while the non-detection of these rhythms after implantation was more due to the surgical aggression.
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  • 99
    ISSN: 1432-1912
    Schlagwort(e): Key words Blood pressure ; GR127935 ; Hypotension ; 5Hydroxytryptamine ; 5ht7Receptor ; Rat ; Sumatriptan
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract It has been suggested that the late hypotensive response to serotonin (5hydroxytryptamine; 5HT) in vagosympathectomized rats is mediated by ‘5HT1like’ receptors since this effect is mimicked by 5carboxamidotryptamine (5CT), is not modified by cyproheptadine, ketanserin or MDL72222, but it is blocked by methysergide. The present study was set out to reanalyze this suggestion in terms of the classification schemes proposed in 1994 and 1996 by the NCIUPHAR subcommittee on the classification and nomenclature of 5HT receptors. I.v. bolus injections of 5CT (0.010.3μg·kg1), 5HT (130μg·kg1) and 5methoxytryptamine (5MeOT; 130μg·kg1) produced dosedependent hypotensive responses with a rank order of agonist potency: 5CT 〉〉 5HT ≥ 5methoxytryptamine with sumatriptan (301000μg·kg1) inactive. The depressor responses to 5HT and 5CT were not attenuated by i.v. GR127935 (3003000μg·kg1) or equivalent volumes of saline. In contrast, lisuride, methiothepin, mesulergine, metergoline and clozapine dose-dependently antagonized the responses to 5HT and 5CT; the rank order of apparent pA2 values against 5HT and 5CT, respectively, was: lisuride (7.7; 7.8) 〉 methiothepin (6.8; 7.0) ≥ mesulergine (6.4; 6.6) 〉 clozapine (5.7; 5.8); metergoline displayed variable potencies (5.6; 6.4). Except for lisuride, which also affected isoprenalineinduced hypotension, the antagonism by the other drugs was selective. Based upon the above rank order of agonist potency, the blockade by a series of drugs showing high affinity for the cloned 5ht7 receptor and the lack of blockade by GR127935, our results indicate that the 5HT receptor mediating hypotension in vagosympathectomized rats is operationally similar to other putative 5ht7 receptors mediating vascular and nonvascular responses (e.g. relaxation of the rabbit femoral vein, canine coronary and external carotid arteries and guineapig ileum as well as feline tachycardia).
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 100
    ISSN: 1432-1912
    Schlagwort(e): Key words Urinary bladder ; Hyperreflexia ; Tachykinin antagonists NK1 receptors ; Tachykinin antagonists ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study investigates the role of tachykinin NK1 and NK2 receptors in motor responses induced by the intravesical instillation of capsaicin in urethane-anaesthetized rats. SR 140,333 (1 µmol/kg, i.v.), a non-peptide NK1 receptor antagonist, abolished urinary bladder contractions induced by the selective NK1 receptor agonist [Sar9]SP-sulfone (0.1-100 nmol/kg, i.v.) without affecting those induced by the NK2 receptor agonist [ßAla8]NKA(4-10). MEN 11,420 (100 nmol/kg, i.v.), a cyclic peptide NK2 receptor antagonist, abolished bladder contractions induced by [ßAla8]NKA(4-10) (0.3-300 nmol/kg, i.v.) without modifying those induced by [Sar9]SP-sulfone. Intravesical instillation of capsaicin (6 nmol/0.6 ml/rat) produced a motor response consisting in a primary contraction followed by a series of high amplitude phasic contractions. The intravesical instillation of saline (0.6 ml/rat) produced a primary contraction of lower amplitude with respect to that induced by capsaicin and the total area under the curve was also lower in saline-instilled rats, however the number and the amplitude of phasic contractions was similar to that induced by capsaicin. MEN 11,420 (100 nmol/kg, i.v.) did not modify motor responses induced by the intravesical administration of saline. In contrast, in capsaicin-instilled rats, MEN 11,420 (100 nmol/kg, i.v.) reduced the primary contraction, the area under the curve and also the number of phasic contractions. SR 140,333 (1 µmol/kg, i.v.) reduced the primary contraction but not other parameters. The combination of SR 140,333 (1 µmol/kg, i.v.) and MEN 11,420 (100 nmol/kg, i.v.) produced an additive inhibitory effect on the primary contraction but not a further inhibition on other parameters with respect to that observed with MEN 11,420 alone. In hexamethonium (110 µmol/kg, i.v.)-pretreated animals the intravesical instillation of capsaicin produced a tonic contraction having greater amplitude and area than that induced by saline. MEN 11,420, but not SR 140,333, significantly reduced the bladder response to capsaicin in hexamethonium-pretreated rats. Again, the combined administration of MEN 11,420 and SR 140,333 did not produce further inhibitory effect in comparison to MEN 11,420 alone. It is concluded that the motor responses induced by the intravesical instillation of capsaicin are mediated by the activation of peripheral tachykinin NK2 receptors.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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