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  • Cell & Developmental Biology  (8)
  • epilepsy  (5)
  • Adaptation, Physiological  (2)
  • 1
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    Mechanisms of adaptation in a predator-prey arms race: TTX-resistant sodium channels (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2002-08-24
    Beschreibung: Populations of the garter snake Thamnophis sirtalis have evolved geographically variable resistance to tetrodotoxin (TTX) in a coevolutionary arms race with their toxic prey, newts of the genus Taricha. Here, we identify a physiological mechanism, the expression of TTX-resistant sodium channels in skeletal muscle, responsible for adaptive diversification in whole-animal resistance. Both individual and population differences in the ability of skeletal muscle fibers to function in the presence of TTX correlate closely with whole-animal measures of TTX resistance. Demonstration of individual variation in an essential physiological function responsible for the adaptive differences among populations is a step toward linking the selective consequences of coevolutionary interactions to geographic and phylogenetic patterns of diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geffeney, Shana -- Brodie, Edmund D Jr -- Ruben, Peter C -- Brodie, Edmund D 3rd -- New York, N.Y. -- Science. 2002 Aug 23;297(5585):1336-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Utah State University, Logan, UT 84322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193784" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Action Potentials ; Adaptation, Physiological ; Animals ; *Biological Evolution ; Colubridae/*physiology ; Drug Resistance ; Linear Models ; Locomotion/drug effects ; Muscle Fibers, Skeletal/drug effects/physiology ; Muscle, Skeletal/drug effects/*physiology ; Neuromuscular Junction/drug effects/physiology ; Predatory Behavior ; *Salamandridae/metabolism ; Skin/chemistry ; Sodium Channels/*drug effects/physiology ; Tetrodotoxin/*toxicity ; United States
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
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  • 2
    Digitale Medien
    Digitale Medien
    The effects of chronic carbamazepine treatment on haem biosynthesis in man and rat (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 241-247 
    Details
    ISSN: 1432-1041
    Schlagwort(e): carbamazepine ; porphyria ; epilepsy ; haem biosynthesis ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The anticonvulsant drug carbamazepine has been reported to produce a condition clinically and biochemically similar to acute intermittent porphyria (AIP). We have determined the effect of chronic carbamazepine treatment on the activities of the enzymes of haem biosynthesis in circulating blood cells and on the urinary excretion of porphyrins and their precursors in 53 epileptic patients receiving monotherapy and in 42 age- and sex-matched controls. In the patients the mean activity of leucocyte 5-aminolaevulinic acid (ALA) synthase, the rate-limiting enzyme of the pathway, was 218% of control values (p〈0.001) and ALA-dehydratase activity was reduced by 37% (p〈0.001). Circulating carbamazepine concentrations correlated negatively with ALA dehydratase (r s=−0.45;p〈0.01). Porphobilinogen deaminase and uroporphyrinogen decarboxylase appeared unaffected by carbamazepine treatment. Significant quantitative increases in the urinary excretion of porphobilinogen and total porphyrins (bothp〈0.05) accompanied the changes in enzyme activity. Similar dose-dependent effects on ALA synthase and ALA dehydratase were shown to occur in rats treated for 5 days with 3 different doses of carbamazepine. These findings further support the porphyrinogenicity of carbamazepine, but the pattern of enzyme alteration differs from that found in AIP.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558260
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  • 3
    Digitale Medien
    Digitale Medien
    Controlled evaluation of a supplementary dose of carbamazepine on psychomotor function in epileptic patients (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 195-199 
    Details
    ISSN: 1432-1041
    Schlagwort(e): carbamazepine ; epilepsy ; anticonvulants ; psychomotor function
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of an additional dose of 400 mg carbamazepine (CBZ) on a series of simple psychomotor tests was investigated in 8 patients with epilepsy receiving chronic CBZ monotherapy in a balanced randomised double-blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free CBZ and CBZ 10,11 epoxide (CBZ-E) concentrations were performed at 10, 12, 14, 16 and 18 h after the extra dose which was administered at 23.00 h on the previous evening. The CBZ increment produced significant impairment of (i) choice reaction recognition time from 10–16 h after the dose (ii) total choice reaction time at 12 h (iii) card sorting at 12 h (iv) sedation scoring at 12 h. No significant effect on critical flicker fusion threshold, finger tapping or simple memory testing was noted. No patient reported increased side-effects in the placebo phase while 5 noted new symptoms likely to be attributable to the additional CBZ. Areas under the concentration-time curves from 10–18 h were higher following CBZ than placebo for total and free CBZ and CBZ-E concentrations. This study has demonstrated decrements in performance of a series of simple psychomotor tests in epileptic patients receiving a supplemental CBZ dose. Patients with epilepsy who require high CBZ concentrations for optimal control of seizures may be at risk of concurrent impairment of psychomotor function. Simple objective measures of performance may help in assessing the benefit-risk ratio.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606658
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  • 4
    Digitale Medien
    Digitale Medien
    Psychomotor impairment and anticonvulsant therapy in adult epileptic patients (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 655-660 
    Details
    ISSN: 1432-1041
    Schlagwort(e): epilepsy ; anticonvulsants ; psychomotor function ; therapeutic drug monitoring
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using a battery of simple tests, psychomotor performance was assessed in 11 healthy subjects, 14 untreated epileptic patients and 66 epileptics on chronic anticonvulsant medication. Significant differences were found between controls and untreated patients for choice reaction time, card sorting and Simple Simon memory game. Treated patients performed less well than both untreated epileptics and controls in choice reaction time (p〈0.05; p〈0.001), card sorting (p〈0.01; p〈0.001), Simple Simon (p〈0.05; p〈0.001) and finger tapping (p〈0.05; p〈0.001). Patients with centrencephalic epilepsy were slower than those with discrete focal EEG abnormalities in reaction time and card sorting. Patients receiving treatment with carbamazepine, phenytoin or sodium valproate alone all performed similarly to each other and to those patients taking anticonvulsant polypharmacy. Monotherapy patients with potentially “toxic” plasma anticonvulsant concentrations did no worse than those within or below the “therapeutic” range. Both the disease and its treatment reduce psychomotor performance. All major anticonvulsants appear to cause a similar degree of impairment across a wide range of concentrations. The effect of chronic anticonvulsant medication on “quality of life” should not be neglected in the pursuit of perfect seizure control.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00541291
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  • 5
    Digitale Medien
    Digitale Medien
    Thyroid hormone concentrations in epileptic patients (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 213-216 
    Details
    ISSN: 1432-1041
    Schlagwort(e): epilepsy ; thyroid hormones ; anticonvulsants ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volunteers were included as controls. Total thyroxine (T4) concentrations were reduced in patients taking enzyme-inducing drugs (carbamazepine and/or phenytoin) compared with both controls and patients taking sodium valproate. Similar differences were shown with each individual drug. All nine patients whose circulating T4 was below the lower limit of the reference range were taking enzyme inducers. Free thyroxine concentrations were also reduced in individuals treated with carbamazepine and phenytoin with five values falling beneath the reference range. Tri-iodothyronine and thyrotropin appeared unaffected by anticonvulsant administration. Thyrotropin releasing hormone stimulation revealed no true hypothyroidism. The lowering effect of anticonvulsant drugs on circulating total and free T4 was not exhibited by the non-inducing sodium valproate. These data support the influence of enzyme induction as a likely mechanism for reduced thyroxine concentrations in treated epileptic patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558149
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  • 6
    Digitale Medien
    Digitale Medien
    Effect of carbamazepine on psychomotor performance in näive subjects (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 37-42 
    Details
    ISSN: 1432-1041
    Schlagwort(e): carbamazepine ; psychomotor function ; anticonvulsants ; epilepsy ; healthy subjects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of a single dose of carbamazepine (CBZ), 10 mg kg−1, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10, 11 epoxide concentration were performed at 10, 12, 14, 16, 18 and 34 h after oral dosing (23.00 h the previous evening). CBZ impaired i) critical flicker fusion threshold frequency at all time points up to 18 h (p〈0.005); ii) total choice reaction time at 10 h (p〈0.005) and 18 h (p〈0.008); iii) card sorting at 14 h (p〈0.001). No significant effect on finger tapping was noted. Subjects adjudged themselves more sedated on CBZ as compared to placebo at 12, 14 and 16 h (p〈0.008). Plasma total and free CBZ concentrations (mean ± SD) peaked at 10 h (8.8±0.2 mg l−1) and 16 h (1.88±0.3 mg l−1) after dosing respectively. CBZ 10, 11 epoxide values were all less than 10% of total CBZ concentrations and, therefore, were unlikely to contribute to the pharmacodynamic effect. Total choice reaction time was significantly more impaired in females (p〈0.05) but no sex difference occurred with the other tests or CBZ concentrations at any time point. No significant correlations were found between individual total or free CBZ concentrations and corresponding test performances at each time point. This study has demonstrated impairment of psychomotor function following CBZ in healthy subjects using a series of simply performed tests. This approach can now be applied to patients with epilepsy receiving long-term treatment with CBZ and other anticonvulsants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614193
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  • 7
    Digitale Medien
    Digitale Medien
    Facial musculature, nerves and blood vessels of the hamster in relation to the cheek pouchPart of the material in this article was presented by the junior author to the faculty of Boston University in partial fulfillment of the requirements for the degree of Master of Arts. (1948)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 83 (1948), S. 149-180 
    Details
    ISSN: 0362-2525
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/jmor.1050830202
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  • 8
    Digitale Medien
    Digitale Medien
    Role of Na-K ATPase in regulation of resting membrane potential of cultured rat skeletal myotubes (1987)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 130 (1987), S. 191-198 
    Details
    ISSN: 0021-9541
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Notizen: The role of Na-K ATPase in the determination of resting membrane potential (Em) as a function of extracellular K ion concentration was investigated in cultured rat myotubes. The Em of control myotubes at 37°C varied as a function of (K+)0 with a slope of about 58-60 mV per ten-fold change in (K+)0. Inhibition of the Na-K pump with ouabain or by reduced temperature revealed that this relation consists of two components. One, between (K+)0 of 10 and 100 mM, remains unchanged by alterations in enzyme activity; The second, between (K+)0 of 1 and 10 mM, is related to the amount of Na-K pump activity, the slope decreasing as pump activity decreases. Indeed, with complete inhibition of the Na-K pump, Em does not change over the range of (K+)0 1 to 10 mM. Measurements of 86Rb efflux and input resistance of individual myotubes showed that membrane permeability does not change as (K+)0 increases from 1 to 10 mM but increases as (K+)0 increases further. Monensin, which increases Na ion permeability, increases Em at values of external K+ below 10 mM, and is without effect at higher values of K+ concentration. The effect of monensin is blocked by ouabain. Tetrodotoxin, which blocks voltage-dependent Na+ channels, decreases Em at low (2-10 mM) K+. We conclude that changes in Em as a function of extracellular K+ concentration in the physiological range are not adequately explained by the diffusion potential hypothesis of Em, and that other theories (electrogenic pump, surface-absorption) must be considered.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/jcp.1041300204
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  • 9
    Digitale Medien
    Digitale Medien
    Nuclear maturation of follicle-enclosed rat oocytes during inhibition of steriodogenesis (1983)
    New York, NY : Wiley-Blackwell
    Gamete Research 8 (1983), S. 79-86 
    Details
    ISSN: 0148-7280
    Schlagwort(e): rat oocytes ; meiosis ; steriodogenesis ; inhibitors ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: This study examined the possible role of steriods in meiotic maturation of preovulatory oocytes. Follicles were isolated from PMSG-treated immature rats and incubated with or withour LH in the presence of one of four inhibitors of steroidogenesis. The inhibitors employed had different sites of attack in the steriodogenic pathway and were aminoglutethimide, cyanoketone, SU 10603 (17β-hydroxylase inhibitor), and 4-OH-androstenedione (aromatase inhibitor). As predicted, the inhibitors drastically altered the pattern of steroid production. None of the inhibitors, however, changed the proportion of oocytes resuming or completing meiosis in response to LH, and there was also no effect of the inhibitors on the oocytes in the absence of LH. It was concluded that steriods are not required for preovulatory nuclear maturation of oocytes in the rat.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/mrd.1120080109
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  • 10
    Digitale Medien
    Digitale Medien
    Nerve growth factor and fibroblast growth factor influence post-fusion expression of Na-channels in cultured rat skeletal muscle (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 144 (1990), S. 492-497 
    Details
    ISSN: 0021-9541
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Notizen: We have examined effects of nerve growth factor (NGF) and fibroblast growth factor (FGF) on the density of tetrodotoxin (TTX)- sensitive Na-channels in cultured rat skeletal muscle. Measurements were made of specific binding of [3H] saxitoxin (STX) and the frequency and rate of rise of spontaneously occurring action potentials, the Physiological expression of Na-channel density. Cells were transferred to various growth conditions at 6 days in vitro, and measurements were made beginning 24 hr later. Both growth factors (GF) caused dose-related in creases in Na-channels compared with myotubes maintained in normal, serum-supplemented growth medium. Maximum effects occurred with a concentration of NGF of 50 ng/ml and FGF of 15 ng/ml. Scatchard analysis of specific STX binding showed an increase in Bmax with no significant change in Kd. Similar increases occurred on rate of rise and frequency spontaneous action potentials. Treatment of cultures with cycloheximide or actinomycin D, inhibitors of protein and RNA synthesis, completely prevented the increase in STX-binding induced by GF treatment, The results indicate that NGF and FGF have important effects on regulation of excitable cell gene products after differentiation.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/jcp.1041440317
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