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  • Engineering General  (6)
  • Life and Medical Sciences  (6)
  • pharmacokinetics  (5)
  • Glucose  (2)
  • Gynogenesis  (2)
  • IAPS-forskolin  (2)
  • 1
    ISSN: 1432-1912
    Keywords: Glucose transport ; IAPS-forskolin ; Insulin-regulated glucose transporter GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK-) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glucose ; B cell ; albino mouse ; membrane potential ; spike frequency ; insulin release ; islet perifusion ; islet of Langerhans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method has been developed for the simultaneous measurement of insulin release and electrical activity in single micro-dissected mouse islets of Langerhans. The effects of D-glucose have been studied in individual islets. Each islet was exposed to 0, 5.6, 11.1, 16.7, 22.2, 27.8 and 33.3 mmol/l glucose in a stepwise fashion. The minimum glucose concentration required to elicit spike activity is lower than that required to stimulate insulin release above basal levels and the maximum spike frequency occurs at a lower glucose concentration than does maximum insulin release. Following a reduction in glucose from 27.8 (or 33.3) to 5.6 mmol/l, membrane potentials returned to resting values within 2 min whereas insulin returned to basal values after 20 min. Increasing glucose from 5.6 to 27.8 mmol/l induced spike activity within 10 s; the insulin response was detected within 40 s. Thus, it is possible to use the single mouse islet for simultaneous measurements of insulin release and electrical activity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: Key words Glucose transport ; IAPS-forskolin ; Insulin-regulated glucose transporter GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK–) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1988), S. 629-635 
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; posture ; intramuscular administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have produced conflicting results as to whether changes in posture affected the pharmacokinetics of the penicillins. We have studied the pharmacokinetics of intramuscularly administered benzylpenicillin in normal subjects during bedrest and ambulation and compared it with data obtained following intravenous administration of the same dose to the same subjects under the same conditions. The values of area under the curve, total clearance, mean residence time and renal clearance found during ambulation were 1175 (min·min·l−1), 488 (ml·min−1), 101 (min), and 264 (ml·min−1) (means). The corresponding values for bedrest were 1032 (min·mg·l−1), 544 (ml·min−1), 96.7 (min), and 315 (ml·min−1). There was a significant difference between the areas under the curve with change of posture but not between any of the other pharmacokinetic variables. The differences observed in this study are unlikely to be of clinical relevance. We suggest that the differences between the results of this study and those of previous studies may be related to the level of exercise undertaken by the subjects in the various studies.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 40 (1991), S. 405-409 
    ISSN: 1432-1041
    Keywords: Metoprolol ; lorazepam ; bromazepam ; interaction ; psychomotor tests ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction between metoprolol and bromazepam and lorazepam was studied in 12 healthy male volunteers aged 21–37 years. Metoprolol had no significant effect on the pharmacokinetics of bromazepam or lorazepam. However, bromazepam AUC was 35% higher in the presence of metoprolol. Bromazepam enhanced the effect of metoprolol on systolic blood pressure but not on diastolic blood pressure or pulse rate. Lorazepam had no effect on either blood pressure or pulse. Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study. Metoprolol caused a small increase in critical flicker fusion threshold with lorazepam but had no effect on the other tests. Lorazepam (2 mg) was more potent than bromazepam (6 mg) in the doses used in this study. The interaction of metoprolol with bromazepam and lorazepam is unlikely to be of clinical significance. No change in dose is necessary when using these drugs together.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 731-734 
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4±100.5 ml/min, 36.23±13.45 min, and 309.4±93.4 ml/min (means ± SD). The corresponding values for bedrest were 543.6±122.6 ml/min, 35.27±10.21 min, and 324.1±145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 82 (1991), S. 144-152 
    ISSN: 1432-2242
    Keywords: Sex determination ; Oreochromis niloticus ; Gynogenesis ; Sex reversal ; Triploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Established techniques of genetic manipulation were used to elucidate sex-determining mechanisms in the commercially important tilapia, Oreochromis niloticus. Analysis of sex ratios from single-pair matings of normal broodstock showed these to be heterogeneous, with an asymmetrical frequency distribution. Data were homogeneous, with the exclusion of a number of broods with sex ratios not significantly different from 3∶1 (male: female), and further progeny testing revealed atypical female heterogamety in the parents of these broods. Analysis of sex ratios from complete diallele-type crosses using five males and five females demonstrated no association between male parent, female parent and progeny sex ratio. Sex ratios of gynogens (0∶1) and triploids (1∶1), and from progeny testing of sex-reversed males (0∶1) and sex-reversed females (3∶1), provide evidence for female homogamety in this species. Progeny testing of male gynogens derived from sex-reversed females demonstrated recombination between the centromere and the sex-determining locus (68.9%). Novel YY “supermales” were shown to be viable and produced all-male offspring. It was concluded that this species exhibits monofactorial, genotypic sex determination with male heterogamety. However, rare autosomal or environmental sex-modifying factors may account for occasional deviations from expected sex ratios.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 82 (1991), S. 153-160 
    ISSN: 1432-2242
    Keywords: Sex determination ; Oreochromis aureus ; Gynogenesis ; Sex reversal ; Hybridisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Sex ratios from 62 single-pair matings of normal broodstock O. aureus were highly heterogeneous with an overall deficit of males (41.4%). Peaks in the sex ratio frequency distribution occurred at 1∶1, 3∶5 and 1∶3 (male∶female). Hybridisation of O. aureus with O. mossambicus, O. spilums and O. niloticus produced highly variable sex ratios, suggesting a complexity of hybrid sex determination. Few valid inferences could be made regarding intraspecific sex determination from these hybrid data. Sex ratios from progeny testing of sex-reversed males (1∶3) and most sex-reversed females (1∶0) provide evidence for female heterogamety in O. aureus. Several aberrant ratios observed suggest Mendelian inheritance of an autosomal recessive gene (F,f), epistatic to the major sex-determining gene (W,Z). Sex ratios of triploids and gynogens support the hypothesis of recombination between the centromere and the major sex-determining locus. Progeny testing of a female mitogyne demonstrated the viability of a novel WW “superfemale”, which gave only female offspring. Not all data could be explained by a two-factor model of sex determination. Further exceptional sex ratios may be accounted for by rare autosomal or environmental sex-modifying factors. It is concluded that O. aureus has a multifactorial mechanism of sex determination with the underlying primary mechanism of female heterogamety.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; 6-mercaptopurine ; targeted drug delivery ; renal transplantation ; intraarterial infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We developed a canine renal allograft model utilizing implantable infusion pumps and biocompatible catheters to investigate the pharmacokinetics of local immunosuppressive drug administration. Seven mongrel dogs underwent bilateral nephrectomy and autotransplantation of one kidney to the iliac vessels. The proximal end of an infusion catheter directed into the iliac artery was tunneled to a subcutaneously placed programmable pump. A second, sampling catheter was placed with its tip in the iliac vein. Simultaneous regional (iliac vein) and systemic (jugular vein) venous concentrations of 6-mercaptopurine (6-MP), the immunosuppressive metabolite of azathioprine, were determined during a continuous 24-h intraarterial infusion (10 mg/kg/24 hr). The gradient between regional and systemic 6-MP concentrations was maximal initially when the pump was turned on, continuously decreased until steady state was reached, and disappeared immediately after the pump was turned off. The mean ratio of steady-state iliac vein to systemic 6-MP concentrations was 5.0 ± 1.4, demonstrating a pharmacokinetic advantage of continuous intraarterial 6-MP infusion to the autotransplanted kidney. The novel canine renal allograft model described herein overcomes the technical limitations of earlier models and represents a foundational step in the design of intrarenal infusion patterns of immunosuppressive agents which we expect to prolong survival of the allotransplanted kidney with minimal systemic drug exposure and side effects.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 24 (1987), S. 725-741 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A monomial treatment for solving mixed equality/inequality constrained generalized geometric programs is presented. The method is shown to be equivalent to a Newton-Raphson procedure carried out in log space on the equality constraints at the same time that a cutting plane procedure is performed on a convex region constrained within the feasible region of the inequality constraints. Known limitations of this monomial treatment are outlined and a technique for improving the efficiency of the GGP method is suggested. A discussion of how other methods of solving mixed equality/inequality constrained GGP problems compare to the monomial treatment is presented and two example problems are solved.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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