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  • Mice  (87)
  • pharmacokinetics  (55)
  • American Association for the Advancement of Science (AAAS)  (83)
  • Springer  (59)
  • 1980-1984  (142)
  • 1965-1969
  • 1925-1929
  • 1980  (142)
Collection
Keywords
Publisher
  • American Association for the Advancement of Science (AAAS)  (83)
  • Springer  (59)
Years
  • 1980-1984  (142)
  • 1965-1969
  • 1925-1929
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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sodium valproate in epileptic patients: Prediction of maintenance dosage by single-dose study (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 71-77 
    Details
    ISSN: 1432-1041
    Keywords: sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic analysis of the plasma valproic acid concentration-time course, following a single oral dose (600 mg) of sodium valproate, was performed in 20 epileptic patients as an aid to the prediction of a proper chronic dosage regimen. A simple one-compartment model was found inadequate to describe the drug concentration-time course in 15 of the 20 patients studied. The average elimination (β phase) half-life of 9 h was shorter than that previously reported in healthy subjects. The latter observation and the wide variation in plasma valproic acid clearance observed between patients (0.09–0.53 ml/kg/min) may have been related to its altered disposition by concomitant anticonvulsant therapy. Sodium valproate maintenance therapy, determined by single-dose pharmacokinetic prediction of steady-state plasma valproic acid levels, did not require dosage adjustment because of unwanted effects. However, the occurrence of drug-related adverse events led to dosage reduction in 4 of 9 patients whose chronic therapy was not pharmacokinetically predicted. Moreover, the pharmacokinetic variability demonstrated for sodium valproate by patients on multiple therapy, whose chronic sodium valproate therapy was pharmacokinetically predicted, indicates the value of monitoring plasma valproic acid levels for the regulation of anticonvulsant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561679
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  • 2
    Electronic Resource
    Electronic Resource
    Metabolic and haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 81-86 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562614
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 4
    Electronic Resource
    Electronic Resource
    Plasma and salivary pharmacokinetics of dapsone estimated by a thin layer chromatographic method (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 129-133 
    Details
    ISSN: 1432-1041
    Keywords: dapsone ; salivary drug elimination ; pharmacokinetics ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high performance thin layer chromatographic assay for dapsone is described with a minimum level of detection of 20 ng ml−1 which is suitable for the study of dapsone pharmacokinetics in plasma and saliva. 100 mg dapsone was administered orally to seven normal adult volunteers, the mean plasma pharmacokinetic parameters were: α=0.23 h−1; β=0.0236 h−1, and t1/2β=30.2 h. Dapsone is also eliminated into the saliva and the t1/2 may be determined via its estimation in saliva. It is 73% bound to plasma protein and the saliva/plasma concentration ratio was found to be 27%. In two subjects the free plasma dapsone concentration was identical to the simultaneous salivary dapsone concentration. Therefore the salivary dapsone concentration is a measure of the free plasma fraction of dapsone. Saliva/plasma dapsone concentration ratios show no time or concentration dependence and little inter-individual variation but are unsuitable for acetylator phenotype determination because monoacetyldapsone is not eliminated in the saliva.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562621
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sotalol after chronic administration to patients with renal insufficiency (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561389
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  • 6
    Electronic Resource
    Electronic Resource
    Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    Details
    ISSN: 1432-1041
    Keywords: desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874666
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  • 7
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of alcuronium chloride in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    Details
    ISSN: 1432-1041
    Keywords: alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t1/2β), apparent volume of distribution (Vdβ), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 µg/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 µg/ml.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570163
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  • 8
    Electronic Resource
    Electronic Resource
    Paracetamol pharmacokinetics in thyroid disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 269-273 
    Details
    ISSN: 1432-1041
    Keywords: paracetamol ; thyrotoxicosis ; hypothyroidism ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n=7) and hypothyroidism (n=4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563010
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetic of 2-(p-methylallylaminophenyl) propionic acid, alminoprofene, in man after single and multiple oral doses (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 419-422 
    Details
    ISSN: 1432-1041
    Keywords: alminoprofene ; antalgic ; pharmacokinetics ; single dose ; multiple doses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-(p-methylallylaminophenyl) propionic acid, alminoprofene (INN), a new antalgic drug, was administered orally to men as a single (300 mg) and multiple doses (300 mg three times daily). Plasma and urine concentrations of alminoprofene were determined by gas-liquid chromatography. After the single oral dose, the peak plasma level (36.2 to 41.5 mg/l) was reached within 0.5–1.5 h. The biological half-life ranged from 2.5 to 3.2 h. During chronic administration of alminoprofene, steady-state equilibrium quilibrium was etablished within 24 h. The urinary excretion of alminoprofene as unchanged product and as glucuronide was very important.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636796
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and oral bioavailability of pyridostigmine in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    Details
    ISSN: 1432-1041
    Keywords: pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636797
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  • 11
    Electronic Resource
    Electronic Resource
    Rapid prediction of steady-state serum theophylline concentration in patients treated with intravenous aminophylline (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    Details
    ISSN: 1432-1041
    Keywords: aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration)=−0.22±1.97 mg/l (mean ± SD); r=0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error=0.58±3.88, r=0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error=3.62±13.36, r=0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874658
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  • 12
    Electronic Resource
    Electronic Resource
    Lack of pharmacokinetic interaction of colestipol and fenofibrate in volunteers (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 459-463 
    Details
    ISSN: 1432-1041
    Keywords: colestipol ; fenofibrate ; fenofibric acid ; pharmacokinetics ; interaction ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of a pharmacokinetic interaction between two hypolipidemic drugs, colestipol, an ion exchange resin, and fenofibrate, a phenoxyacid derivative, was studied in 6 male volunteers. The investigation followed a four-step protocol during 18 days, and relied on determination of plasma and urinary levels of fenofibric acid, the active metabolite of fenofibrate. The kinetics of a single dose of fenofibrate 300 mg was established over 3 days. Thereafter, from Days 4 to 9 fenofibrate was given daily as 200 mg in the morning and 100 mg in the evening; the plasma fenofibric acid level reached about 10 µg/ml. From Days 9 to 15 the same dose of fenofibrate was administered together with colestipol 10 g in the morning and 5 g in the evening. Plasma fenofibric acid concentrations remained unchanged and the 24 h urinary excretion of fenofibric acid did not fall. On Day 15, a last single dose of fenofibrate 300 mg was given with colestipol 15 g. The pharmacokinetic pattern of fenofibric acid on Days 15 to 18 did not differ significantly from that found previously (Days 1 to 3). From these results, it is likely that there is no pharmacokinetic interaction between the two hypolipidemic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570164
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  • 13
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and clinical response (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 51-53 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; phenobarbital ; aminoglycoside antibiotics ; pharmacokinetics ; clinical response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561478
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  • 14
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diuretics and methylxanthines in the neonate (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 55-63 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; furosemide ; caffeine ; theophylline ; neonate ; pharmacokinetics ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of diuretics and methylxanthines is considerably slower in the neonate than in the adult. Dose guidelines, especially during long term maintenance, must be adjusted to account for this slower drug elimination. Pharmacokinetic studies and the requisite pharmacologic evaluation on diuretics such as hydrochlorothiazide, spironolactone, ethacrynic acid and others should be done. Furosemide undergoes biotransformation in the newborn producing an acid metabolite and a glucuronide conjugate. Methylxanthines are effective in the treatment of neonatal apnea. Plasma elimination of theophylline is exceedingly slow, more so with caffeine. Decreased elimination is partly explained by decreased oxidative biotransformation. Caffeine is excreted in the urine of the newborn mainly unchanged (85%) in contrast to the adult where caffeine is a minor portion of urinary excretion (2%). Theophylline is methylated to caffeine and may possibly exert additive pharmacologic effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561479
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  • 15
    Electronic Resource
    Electronic Resource
    Absorption and disposition of ampicillin in the elderly (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 195-198 
    Details
    ISSN: 1432-1041
    Keywords: ampicillin ; age ; oral dose ; i. v. dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ampicillin (500 mg) was administered intravenously (i. v.) and orally to a small panel of young and elderly subjects in a cross-over fashion. Plasma concentrations of ampicillin were measured by a fluorimetric technique for 8 h following dosage. A two compartment-open model was used to characterise the plasma concentration-time data for the intravenous study, and a one compartment-open model incorporating an absorption lag time and a first-order absorption rate constant for the oral data. Plasma clearance after i. v. ampicillin was found to be significantly decreased in the elderly (P〈0.05, 0.08 1 h−1kg−1 versus 0.18 1 h−1kg−1), and half life and area under the plasma level-time curve were significantly increased (P〈0.05, 6.70 h versus 1.68 h, t1/2β; p〈0.01, 176.51 µg·h ml−1 versus 37.88 µg·h ml−1, AUC o ∞ ) as compared to the young. No sigificant differences were observed between the age groups for the volume of distribution terms and the changes in drug handling noted in the elderly were attributed to a decrease in the renal elimination of ampicillin. Following oral administration a significant increase in t1/2β, AUC o ∞ and the maximum plasma concentration (Cpmax P〈0.01, 6.59 µg ml−1 versus 3.42 µg ml−1) of ampicillin was found in the elderly subjects. These findings were similarly attributed to a decrease in drug elimination in the aged, since no apparent age differences were noted in the pharmacokinetic parameters governing both rate and extent of ampicillin absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561590
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  • 16
    Electronic Resource
    Electronic Resource
    Effects and pharmacokinetics of isosorbide dinitrate in normal man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 237-244 
    Details
    ISSN: 1432-1041
    Keywords: isosorbide dinitrate ; 2-isosorbide mononitrate ; 5-isosorbide mononitrate ; digital plethysmography ; hypotension ; bradycardia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 18 subjects were given isosorbide dinitrate (ISDN) 5 mg sublingually and serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) were measured, as well as changes in digital plethysmographic amplitude, heart rate, ECG, blood pressure and Schellong's test. ISDN was rapidly absorbed and metabolized, having an elimination half-life of 29 min. Its metabolites 2-ISMN and 5-ISMN had longer half-lives of 1.75 and 7.6 h respectively. The amplitude of the α-wave of the digital plethysmograph did not change significantly either in the predrug period or after placebo administration. It increased within 4 min of administration of ISDN, and reached a maximum after 14 min; the effect lasted for about 2 h. ISDN lowers blood pressure and increases heart rate in most volunteers, but in 3 of the 18 subjects severe hypotension occurred, accompanied by severe, reversible bradycardia, which was probably due to vagal reflexes initiated by the markedly diminished ventricular enddiastolic volume (LVEDV) and pressure (LVEDP). No correlation could be demonstrated between the serum concentration of ISDN and/or its vasoactive metabolites and changes in plethysmographic amplitude.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563005
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  • 17
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics and oral bioavailability of ketobemidone (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    Details
    ISSN: 1432-1041
    Keywords: ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The basic pharmacokinetics and oral bioavailability of ketobemidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin® 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin®, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemidone was 34%±16% (SD, n=6). The mean plasma half-life of elimination (t1/2β) was about the same following oral (2.45±0.73 h; SD, n=5) as after intravenous administration (2.25±0.35 h; SD, n=6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin® (ketobemidone 5–10 mg every 6–7 h) in patients with severe pain is too low.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561676
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  • 18
    Electronic Resource
    Electronic Resource
    A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metoprolol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 87-92 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
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  • 19
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    Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    Details
    ISSN: 1432-1041
    Keywords: flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were no changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10–15 ng/ml after the first and 15–20 ng/ml after the last dose. The β-half-life was found to be between 20 and 36 h.
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    URL: http://dx.doi.org/10.1007/BF00561899
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  • 20
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    Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    Details
    ISSN: 1432-1041
    Keywords: chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
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    URL: http://dx.doi.org/10.1007/BF00625801
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  • 21
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    Pharmacokinetics of naproxen in subjects with normal and impaired renal function (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 263-268 
    Details
    ISSN: 1432-1041
    Keywords: naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7± 3.0 h (mean±SD) and it was not significantly prolonged in patients with renal failure (18.1±5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6± 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
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    URL: http://dx.doi.org/10.1007/BF00563009
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  • 22
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    Pharmacokinetic studies in volunteers of intravenous and oral cis (Z)-flupentixol and intramuscular cis (Z)-flupentixol decanoate in viscoleo® (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 355-360 
    Details
    ISSN: 1432-1041
    Keywords: cis (Z)-flupentixol ; cis (Z)-flupentixol decanoate ; serum concentration ; biological half-life ; pharmacokinetics ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations of cis (Z)-flupentixol have been estimated in three male human volunteers who received cis (Z)-flupentixol by intravenous infusion, flupentixol (cis (Z)/trans (E) mixture, 1:1) orally as single and repeated doses, and i. m. cis (Z)-flupentixol decanoate in Viscoleo®. The intravenous data show that cis (Z)-flupentixol followed a multicompartment model, but it was not possible to fit the data to a two or three compartment model. The concentration curves after oral administration indicated relatively slow absorption with a peak concentration at 3–6 h, except for one case with peak at 1 h. The variation in the dosage interval after one daily oral administration was relatively limited (1.7–3.0 times), which indicates that 24 h is a reasonable dosage interval. Biological half-lives were estimated in different ways and showed some intra-individual variation; the half-life was of medium length (19–39 h). The serum concentrations after intramuscular injection of cis (Z)-flupentixol decanoate clearly demonstrated a depot effect, with a maximal concentration at 3–5 days after injection. The descending part of the serum curves allowed an approximate estimation of half-life of 3–8 days. This was not the elimination half-life, but in all probability the half-life of release of drug from the oil depot which was the rate-limiting step. From the areas under the serum concentration curves the fraction of orally administered cis (Z)-flupentixol available to the organism was calculated to be 55% (range 48–60%). The loss of drug might have been due to imcomplete absorption, but it is more likely that cis (Z)-flupentixol underwent first-pass metabolism in the gut wall and the liver. As the tablets contained about 50% cis (Z)-flupentixol, while the depot preparation contained 74% cis (Z)-flupentixol, the pharmacokinetically equivalent doses are: 10 mg tablet daily corresponds to 25 mg depot weekly. Calculation of systemic clearance gave values of 0.44–0.49 l/min, and an apparent volume of distribution was 12.5–17.2 l/kg.
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  • 23
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    Time-course of the anti-hypertensive action of atenolol: Comparison of response to first dose and to maintained oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 365-374 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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    URL: http://dx.doi.org/10.1007/BF00636787
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  • 24
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    Pharmacokinetics of acebutolol in patients with all grades of renal failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 339-348 
    Details
    ISSN: 1432-1041
    Keywords: acebutolol ; renal failure ; dialysis ; pharmacokinetics ; N-acetylmetabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acebutolol was studied in 10 healthy subjects with normal renal function (RN), in 13 patients with various degrees of renal failure (RI) and in 8 patients undergoing repeated haemodialysis (RD). A highly specific method was used to measure acebutolol (A) and N-acetylmetabolite (NAM). In RN the decrease in plasma levels was biexponential with an apparent plasma half lives in the slow phase of A: 8.8±2.3 h and NAM: 11.4±2.2 h. The percentage of the dose excreted unchanged was 13.9% and as NAM 25.8%. Renal clearances were A: 167±20 ml/min and NAM: 150±18 ml/min. The apparent plasma half life of acebutolol does not change according to the degree of renal insufficiency (RI: 7.0±2.7 h, RD: 7.5±2.7 h), while that of NAM is increased (RI: 21.5±10.1 h, RD: 32.3±16.8 h). There is a linear relationship between the apparent elimination rate constant of NAM and creatinine clearance (r=0.832,p〈0.001). In RI 21.7% of the dose is excreted in urine (A 5.0%, NAM 16.7%). When renal function is impaired, the renal clearance of A and NAM decrease in parallel with the creatinine clearance (A: r=0.874,p〈0.001; NAM: r=0.954,p〈0.001). During dialysis the plasma half life fell (A=3.4±0.9 h, NAM=7.4±2.6 h). The dialytic clearance was A: 42.6±12.7 ml/min and NAM: 40.4±16.3 ml/min, for a blood flow of 238±35 ml/min through a dialyser with a cuprophane membrane (Ultraflo II Travenol). Acebutolol is taken up by erythrocytes (λbc=0.50±0.04). The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal insufficiency.
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    URL: http://dx.doi.org/10.1007/BF00558446
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  • 25
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    Disposition and clinical pharmacokinetics of microcrystalline theophylline (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
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    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
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    URL: http://dx.doi.org/10.1007/BF00558452
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  • 26
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    Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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    URL: http://dx.doi.org/10.1007/BF00636790
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  • 27
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    Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 279-283 
    Details
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
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    URL: http://dx.doi.org/10.1007/BF00563012
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  • 28
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    Disposition of dibekacin in patients undergoing haemodialysis (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 347-350 
    Details
    ISSN: 1432-1041
    Keywords: dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance 〈5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determined microbiologically by a plate diffusion method usingB. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
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    URL: http://dx.doi.org/10.1007/BF00561393
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  • 29
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    Haemodynamic effects, plasma concentrations and tolerance of orally administered prenalterol in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 383-390 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was studied in six healthy volunteers given single oral doses of 2.5, 5 and 10 mg and placebo. It displayed a distinct positive inotropic action, manifested as a dose-related reduction of 16.5–27.2 msec in the pre-ejection period (PEPc; systolic time-intervals), and an increase of 4.2–5.9 Ω/sec2 in the Heather index (impedance cardiography). There was also a dose-related increase of 17.6–34.0 mmHg in systolic blood pressure, whereas diastolic pressure showed a slight, transient decrease, not related to the dose given. Heart rate rose by 5–12 beats/min. Stroke volume, as determined by impedance cardiography, increased by 24.2–28.5 ml at all three dose-levels. The effects of the drug developed rapidly, reaching their maximum within 30–60 min and lasting for about 4 h. The time-course of the effects corresponded to the plasma concentrations of the drug. The increases in systolic pressure and contractility were linearly correlated with the plasma concentrations (r=0.8−0.9,p〈0.001). The activity of prenalterol was also tested in the same volunteers after blockade of β-receptors with oxprenolol 80 mg. Under these conditions, oral doses of 25, 50 and 100 mg produced effects similar to or slightly less marked than those recorded after doses ten times lower in the absence of β-blockade. In a further 10 healthy volunteers, in whom tolerance to prenalterol was studied by repeated administration for 10 days of 5 mg four times daily, no change in blood chemistry, haematological parameters or urine values was found. The positive inotropic effect of a single oral dose of prenalterol 5 mg was also demonstrated by reference to the systolic time-intervals and the echocardiogram, in six patients with chronic heart failure, five of whom were digitalized. Prenalterol did not give rise to premature concentrations or other arrhythmias. The only untoward effect definitely attributable to the drug was palpitation, which was dose-related and as a rule was not unduly distressing; in one volunteer, however, the palpitations were unbearable. Prenalterol is a cardiostimulant agent with no direct effect on the peripheral circulation. On the basis of its pharmacological activity, it might well be of therapeutic benefit in all conditions in which an improvement in the pumping efficiency of the heart is required.
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  • 30
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    Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
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  • 31
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    Inhibition by idrocilamide of the disposition of caffeine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 37-43 
    Details
    ISSN: 1432-1041
    Keywords: caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
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    URL: http://dx.doi.org/10.1007/BF00561675
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  • 32
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    Altered prazosin pharmacokinetics in congestive heart failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prazosin (Minipress®) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double in the patients in comparison to the control group. Reduction in hepatic blood flow, altered gastrointestinal absorption of the drug or diminished intrinsic hepatic metabolic activity in the patient group may have contributed to the observed changes in prazosin disposition. The finding of higher prazosin plasma concentrations in patients with refractory heart failure demonstrates the need for close monitoring of these individuals following administration of the drug in the treatment of chronic congestive heart failure.
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    URL: http://dx.doi.org/10.1007/BF00570159
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  • 33
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    Placental transfer of pethidine and norpethidine and their pharmacokinetics in the newborn (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
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    ISSN: 1432-1041
    Keywords: pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The literature data available on pethidine and norpethidine kinetics in women in labour and in their newborns is reviewed and compared with recent personal observations. In pregnant women the apparent blood half-life of pethidine is not different from that in healthy controls, however, apparent volume of distribution and total body clearance are reduced. Norpethidine blood levels are measurable after 10–20 min and tend to increase with time. The amount of drug transferred to the foetus is clearly linked to the dose administered to the mother, the dosing-delivery interval and to the metabolic capability of the mother. An equilibrium between maternal and umbilical venous blood is reached 2–3 h after dosing for pethidine and later for norpethidine. In the neonate, the apparent pethidine half-life is 2 to 7 times longer than in adults with values ranging from 7 to 32 h. Norpethidine is actively formed in the newborn with peak blood levels at 12–36 h and an apparent blood half-life of 20–36 h. At the doses usually recommended blood concentrations at birth are frequently higher than those required for analgesia and close to or within toxic ranges. An effort toward a more individualized dosage as well as toward a better understanding of the possible role of norpethidine with regard to adverse effects is needed.
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  • 34
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    Disposition and pharmacodynamics of diuretics and antihypertensive agents in renal disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methyldopa, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.
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    Bromocriptine concentration in saliva and plasma after long-term treatment of patients with Parkinson's disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 171-174 
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    ISSN: 1432-1041
    Keywords: bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.
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    Comparative in vitro effects and in vivo kinetics of antithyroid drugs (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
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    ISSN: 1432-1041
    Keywords: propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
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    Time course of blood pressure, pulse rate, plasma renin and metoprolol during treatment of hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
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    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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    Influence of dose on the pharmacokinetics of Cefadroxil (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
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    ISSN: 1432-1041
    Keywords: cefadroxil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Cefadroxil have been studied in a crossover study involving 20 experiments in four healthy volunteers (19–24 years), after oral administration of five individual doses of 250, 500, 750, 1000 and 1500 mg of the antibiotic in capsules to each person. Plasma and urine concentrations of the antibiotic were determined microbiologically by a plate diffusion method. The antibiotic followed an open, single-compartment kinetic model. The plasma half-life was not significantly influenced by dose; the average was 1.438±0.220 h. The percentage of the antibiotic excreted in urine, too, was not significantly affected by the dose, being close to 80% of the quantity originally administered within 24 h. The values of Cmax and (AUC) increased linearly with the administered dose.
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    Comparative bioavailability of disopyramide after multiple dosing with standard capsules and controlled-release tablets (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
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    ISSN: 1432-1041
    Keywords: disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
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    URL: http://dx.doi.org/10.1007/BF00561902
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    Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
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    ISSN: 1432-1041
    Keywords: L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
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    The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
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    ISSN: 1432-1041
    Keywords: sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
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    Pharmacokinetics and dosage of digoxin in neonates and infants (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
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    ISSN: 1432-1041
    Keywords: digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (〉1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients. The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.
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    Effectiveness and pharmacokinetics of indomethacin in premature newborns with patent ductus arteriosus (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
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    ISSN: 1432-1041
    Keywords: patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A review of the published data on pharmacological closure of PDA in premature newborns shows that doses of 0.2 mg/kg indomethacin are less successful when given enterally (18 to 85% closure) than when given intravenously (88 to 90% closure). The elimination half-life is markedly prolonged in premature newborns compared to adults but there are wide differences between the patients and some discrepancies between mean values reported by various authors. The present study compares clinical and pharmacological results obtained in two groups of low birth weight infants with symptomatic PDA and treated with 0.2 mg/kg indomethacin: 7 patients treated enterally (group A) and 11 patients treated intravenously (group B). Permanent closure of the ductus was observed in 4 cases in group A and in 9 cases in group B. Transient closure was observed twice in each group. Of a total of 18 infants, 15 were saved (83%). One baby treated with indomethacin in spite of preexisting oliguria died from persistent anuria. Indomethacin plasma levels were measured by gas chromatography. The mean elimination half-life of the drug in group A (40.3±12.2 h) did not differ from that in group B (33.9±11.7 h). The apparent plasma half-life appears to be inversely correlated with gestational age (r=0.66,p〈0.05). No relationship between peak plasma levels and ductal closure was established, but a significant difference was found for area under the curve (0 to 24 h) between patients in whom a permanent closure was obtained and those in whom the closure was either transient or absent.
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    Nortriptyline therapy in elderly patients: Dosage prediction after single dose pharmacokinetic study (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
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    ISSN: 1432-1041
    Keywords: antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p〈0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
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    Effect of posture and sleep on pharmacokinetics (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
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    ISSN: 1432-1041
    Keywords: amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.
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    Influence of early pregnancy on reproductive rate in lines of mice selected for litter size (1980)
    Springer
    Theoretical and applied genetics 57 (1980), S. 209-220 
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    ISSN: 1432-2242
    Keywords: Mice ; Early puberty ; Litter size ; Selection ; Reproductive rate ; Pheromone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The influence of male-induced early puberty on female reproductive rate was determined in three lines of mice differing in litter size and body weight. The lines originated from a single base population and had undergone 20 generations of selection for the following criteria: large litter size at birth (L+), large litter size and small 6-week body weight (L+W−), or small litter size and large 6-week body weight (L−W+). Females were paired with a mature intact male of the same line at 3, 5 or 7 weeks of age. Mean mating age, averaged over lines, was 26.5 ± .3, 38.3 ± .3 and 52.7 ± .3 days. Exposure to a mature male accelerated female sexual maturation in each line. When contrasted with their sibs mated at a later age, early-pregnant females from each line exhibited a decline in one or more component of reproductive performance, suggesting that the physiological state of the very young female was not optimum for normal pregnancy. In comparisons of early and later mating ages, all three lines showed a decreased littering rate at first mating, number born alive, and individual birth weight of progeny adjusted for litter size; L+ and L+W− mice showed an increased perinatal mortality rate; L+ and L−W+ had a reduction in litter size at birth. When the L+, L+W− and L−W+ lines were compared with an unselected strain and a line selected for high postweaning gain in similar experiments, a genotype by environment interaction was apparent since all lines did not respond in a similar manner to early mating. The line ranking for litter size at birth for each age at male-exposure was L+〉L+W−〉L−W+, despite the significant line by age interaction. When litter size was adjusted by covariance for body weight at mating, the significant effects of age at male-exposure and line by age interaction were eliminated. All fertile females were remated after they had weaned their first litter to obtain information on litter size in parity two. Line differences in litter size at birth and number born alive were uniform across parities. An age by parity interaction was evident since the decreased fecundity at younger ages of male exposure in the L+ and L−W+ litters of parity one was not evident in parity two. Litter feed efficiency during first parity gestation was defined as litter birth weight divided by either cumulative feed intake of the dam from mating to parturition (GEI) or cumulative feed intake from weaning to parturition (GEII). The ranking of lines for GEI and GEH was L+〉 L+W−〉L−W+, but when feed efficiency was adjusted for littering rate, L+W− and L−W+ were not significantly different. With regard to age at mating, the ranking for GEI (7 wk 〉 5 wk 〉 3 wk) was reversed from GEII (3 wk 〉5 wk 〉 7 wk) and these significant differences were maintained after adjustment for littering rate.
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    Symbols in pharmacokinetics (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 497-507 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; symbols ; notation ; nomenclature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To encourage uniformity in the presentation of pharmacokinetic data, a general nomenclature has been developed. The system has wide application. Flexibility is achieved through the use of general variables, constants, qualifying terms, and subscripts. Yet, through the use of implied terms, the symbols describing many common variables and constants are simple.
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    Identifiable pharmacokinetic models: The role of extra inputs and measurements (1980)
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
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    ISSN: 1573-8744
    Keywords: compartmental analysis ; dynamic response ; identification ; linear systems ; modeling ; parameter estimation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Single input, single output experiments can result in nonunique solutions for the rate constants of a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is an infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtain a unique solution for the others. This paper considers such experiments and determines whether either the addition of an extra input (simultaneously with the first input) or the taking of an extra measurement would result in a unique solution. It is found that perturbing a second input can be useful, but only if the perturbation is of different shape from the first input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, though, the second measurement (for example, by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.
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    Accumulation in the peripheral compartment of a linear two-compartment open model (1980)
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacological effects ; two-compartment model ; tissue accumulation ; aminoglycoside antibiotics ; gentamicin ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Accumulation factors for the peripheral compartment in a two-compartment open model are derived. These expressions are contrasted with some previously published statements concerning drug accumulation. The utility of the new indices of accumulation is illustrated by reference to studies of gentamicin tissue uptake and its proposed relation to nephrotoxicity.
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    Pharmacokinetics of intravenously administered bumetanide in man (1980)
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
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    ISSN: 1573-8744
    Keywords: bumetanide ; diuretics ; pharmacokinetics ; three-compartment model ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disposition of [ 14C] bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.
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    Pharmacokinetics of bretylium in man after intravenous administration (1980)
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
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    ISSN: 1573-8744
    Keywords: bretylium ; pharmacokinetics ; healthy subjects ; antiarrhythmic ; twocompartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2β)of 7.8 hr and apparent volume of distribution (Vd,β)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.
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    Influence of renal failure on the hepatic clearance of bufuralol in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
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    ISSN: 1573-8744
    Keywords: bufuralol ; renal failure ; pharmacokinetics ; metabolites ; renal clearance ; hepatic clearance ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1′-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Bufuralol was given orally to all subjects (20 mg); some of the healthy volunteers also received the drug intravenously (5 mg). Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its halflife of elimination was not markedly influenced. The behavior of 1′-hydroxy-bufuralol was consistent with a decreased renal clearance. The behavior of bufuralol in patients with renal failure was analyzed using the clearance approach. From this analysis it appears that the presystemic biotransformation of bufuralol is decreased in renal failure and that changes in systemic clearance are compensated in our patients by modifications of the volume of distribution, resulting in little net change in the halflife of elimination.
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    Lithium pharmacokinetics: Single-dose experiments and analysis using a physiological model (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 439-461 
    Details
    ISSN: 1573-8744
    Keywords: lithium ; pharmacokinetics ; physiological parameters ; cellular transport ; three-compartment model ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of lithium (Li +) distribution after a single dose was studied in healthy human subjects. Experiments were performed by simultaneously following changes of Li+ concentration in plasma, erythrocytes (RBC), and urine. The data were fitted by a simple but physiologically realistic model, so that extracted rate constants could be assigned to real body compartments and compared with independent measurements of cellular transport characteristics. The extracted rate constants were used to calculate steady-state cell-to-plasma Li+ ratios for RBC and for inaccessible cells (mainly muscle). In both cell types, the intracellular Li+ concentration is far below electrochemical equilibrium. This finding suggests that the Li+ countertransport efflux mechanism of RBC may be shared with muscle. We also present evidence for a circadian rhythm in Li+ excretion that parallels the daily cycle of Na+ and K+ excretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059545
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    Electronic Resource
    Electronic Resource
    A pharmacokinetic model-independent approach for estimating dose required to give desired steady-state trough concentrations of drug in plasma (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 105-110 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; maintenance dose ; dose estimation ; multiple dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A maintenance dose designed to give a desired minimum concentration of drug in plasma at steady-state can be determined in a model-independent manner assuming that concentration-time data needed for the calculation are obtained after absorption and distribution are complete. Using a few concentration-time points obtained after the first dose, numerical values of β and Z, a parameter consisting of different pharmacokinetic parameters for different models, can be obtained. An administration interval (τ) can be chosen based on β. Using the values of β, Z, and τ, a maintenance dose is calculated. This approach will allow calculation of a maintenance dose when drug is present in plasma at the time the first monitored dose is given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059452
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    Electronic Resource
    Electronic Resource
    Heuristic modeling of drug delivery to malignant brain tumors (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    Details
    ISSN: 1573-8744
    Keywords: chemotherapy ; pharmacokinetics ; brain tumors ; modeling ; solid tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the “breakdown” in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059646
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    Electronic Resource
    Electronic Resource
    Unimpaired delayed type hypersensitivity reactions in mice infected withTrypanosoma cruzi strain Y (1980)
    Springer
    Parasitology research 61 (1980), S. 179-185 
    Details
    ISSN: 1432-1955
    Keywords: Trypanosoma cruzi ; Delayed hypersensitivity ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Delayed type hypersensitivity reactions (DTH) to DNFB in C3H (susceptible) and (CBA×C57B1/10)F1 (resistant) mice were not impaired inTrypanosoma cruzi strain Y infections. Mice were infected IP with 100 parasites and sensitized or challenged 11 days after infection at the peak of parasitaemia. DTH reactions were found to be enhanced in C3H infected mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00925463
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    Electronic Resource
    Electronic Resource
    The growth ofHymenolepis microstoma in intact and gonadectomized mice (1980)
    Springer
    Parasitology research 61 (1980), S. 243-247 
    Details
    ISSN: 1432-1955
    Keywords: Hymenolepis microstoma ; Mice ; Orchiectomy ; Ovariectomy ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Gonadectomy or sex of the host had no effect on the mean dry weight ofHymenolepis microstoma examined on day 12 postinfection (p.i.). However, on day 20 p.i. worms from intact or sham-operated male mice were significantly heavier than those recovered from the corresponding groups of female hosts. Orchiectomy of hosts lowered the average weight of these older worms, but ovariectomy had no effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00925515
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    Electronic Resource
    Electronic Resource
    Humoral suppression inTrypanosoma cruzi infection in relation to the timing of antigen presentation (1980)
    Springer
    Parasitology research 64 (1980), S. 85-93 
    Details
    ISSN: 1432-1955
    Keywords: Trypanosoma cruzi ; Immunosuppression ; Immunenhancement ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract (CBA×C57 B1/10)F1 mice infected intraperitoneally with 100 parasites ofTrypanosoma cruzi strain Y developed an infection with acute and chronic phases. Humoral suppression to sheep red blood cells was evident in both phases but enhancement of the response was achieved only at the beginning of the infection. A mitogen secreted by the parasite could explain both phenomenons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00927059
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    Electronic Resource
    Electronic Resource
    Effect of psychotropic drugs on the pharmacokinetics of lithium (1980)
    Springer
    Bulletin of experimental biology and medicine 89 (1980), S. 784-785 
    Details
    ISSN: 1573-8221
    Keywords: lithium ; psychotropic drugs ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00836250
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    L-Ornithine decarboxylase:an essential role in early mammalian embryogenesis (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-05-02
    Description: The highly selective, enzyme-activated, irreversible inhibitor of L-ornithine decarboxylase, DL-alpha-difluoromethylornithine, suppresses the increase in uterine L-ornithine decarboxylase activity associated with early embryogenesis in the mouse and arrests embryonic development at that stage. Contragestational effects were confirmed in the rat and rabbit. An increase in L-ornithine decarboxylase activity that leads to a rapid increase in putrescine concentration appears to be essential during a critical period after implantation for continued mammalian embryonal growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fozard, J R -- Part, M L -- Prakash, N J -- Grove, J -- Schechter, P J -- Sjoerdsma, A -- Koch-Weser, J -- New York, N.Y. -- Science. 1980 May 2;208(4443):505-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6768132" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosylmethionine Decarboxylase/metabolism ; Animals ; Carboxy-Lyases/*physiology ; Eflornithine ; Embryo, Mammalian/drug effects/*physiology ; Female ; Gestational Age ; Mice ; Ornithine/*analogs & derivatives/pharmacology ; Ornithine Decarboxylase/*physiology ; Ornithine Decarboxylase Inhibitors ; Polyamines/metabolism ; Pregnancy ; Rabbits ; Rats ; Uterus/drug effects/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Doridosine: a new hypotensive N-methylpurine riboside from the nudibranch Anisodoris nobilis (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-01-11
    Description: A new N-methylpurine riboside (doridosine), probably N1-Methylisoguanosine, was isolated from the digestive glands of a nudibranch. Doridosine produces prolonged hypotension and bradycardia in anesthetized rats, decreases the rate and the amplitude of contraction of guinea pig atria in vitro, and causes the heart rate in anesthetized mice to be reduced by 50 percent for many hours after which the animals recover completely.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fuhrman, F A -- Fuhrman, G J -- Kim, Y H -- Pavelka, L A -- Mosher, H S -- New York, N.Y. -- Science. 1980 Jan 11;207(4427):193-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7350655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antihypertensive Agents/*isolation & purification ; Guanosine/*analogs & derivatives/isolation & purification/pharmacology ; Guinea Pigs ; Heart Rate/drug effects ; Mice ; Mollusca/analysis ; Rats
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Survival of mice receiving melanoma transplants is promoted by hydroquinone (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-04-25
    Description: In BALB/c female mice with melanoma transplants, the incidence of "takes" is decreased and survival is increased by hydroquinone, a melanocytolytic agent. The mechanism of drug action is suggested by via DNA. The significant and high degree of positive response to hydroquinone treatment in vivo is encouraging for the clinical management of melanoma with melanocytolytic agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chavin, W -- Jelonek, E J Jr -- Reed, A H -- Binder, L R -- New York, N.Y. -- Science. 1980 Apr 25;208(4442):408-10.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7367868" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Hydroquinones/metabolism/*therapeutic use ; Melanocytes/metabolism ; Melanoma/*drug therapy ; Mice ; Neoplasm Transplantation ; Neoplasms, Experimental/drug therapy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Testosterone-mediated sexual dimorphism of mitochondria and lysosomes in mouse kidney proximal tubules (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-08-29
    Description: In kidney proximal tubules of male mice the mitochondria are larger and more electron-lucent, autophagic vacuoles and lysosomes (predominantly myeloid bodies) more numerous and voluminous, and exocytosed intraluminal myeloid bodies more common than in females. Males also have higher kidney activities of mitochondrial cytochrome c oxidase and lysosomal hydrolases, and excrete larger quantities of hydrolases and protein in the urine. Orchiectomy evokes the feminine pattern whereas testosterone administration induces the male pattern. Endogenous testosterone modulates mitochondrial structure and function and enhances the activity of the lysosomal-vacuolar system in proximal tubule cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koenig, H -- Goldstone, A -- Blume, G -- Lu, C Y -- New York, N.Y. -- Science. 1980 Aug 29;209(4460):1023-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7403864" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Castration ; Enzymes/urine ; Female ; Kidney/drug effects ; Kidney Tubules, Proximal/*ultrastructure ; Lysosomes/drug effects/enzymology ; Male ; Mice ; Mitochondria/drug effects/enzymology ; Organ Size/drug effects ; Sex Differentiation/*drug effects ; Testosterone/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Tooth induction in chick epithelium: expression of quiescent genes for enamel synthesis (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-02-29
    Description: Intraocular grafts of chick epithelium combined with mouse molar mesenchyme produced a variety of dental structures including perfectly formed crowns with differentiated ameloblasts depositing enamel matrix. The results suggest that the loss of teeth in Aves did not result from a loss of genetic coding for enamel synthesis in the oral epithelium but from an alteration in the tissue interactions requisite for odontogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kollar, E J -- Fisher, C -- New York, N.Y. -- Science. 1980 Feb 29;207(4434):993-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7352302" target="_blank"〉PubMed〈/a〉
    Keywords: *Amelogenesis ; Animals ; Chick Embryo/*cytology ; Culture Techniques ; Dental Enamel Proteins/*biosynthesis/genetics ; Embryonic Induction ; Epithelial Cells ; Genes ; Mandible/cytology ; Mesoderm/cytology ; Mice ; *Odontogenesis
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Role of the spleen in the growth of a murine B cell leukemia (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-04-04
    Description: A spontaneous B cell leukemia (BCL1) grew progressively in normal BALB/c mice after injection of tumor cells but did not grow in splenectomized recipients. Despite the absence of progressive tumor growth, residual tumor cells with malignant potential were found in the peripheral blood of the splenectomized animals. Splenectomy performed after injection of tumor cells but before the development of marked leukocytosis also prevented progressive tumor growth and death of the host. Thus the spleen appears to be necessary for progressive proliferation of this lymphocytic leukemia early after passage in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kotzin, B L -- Strober, S -- New York, N.Y. -- Science. 1980 Apr 4;208(4439):59-61.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6965803" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*pathology ; Disease Models, Animal ; Female ; Leukemia, Experimental/etiology/physiopathology ; Leukemia, Lymphoid/*etiology/physiopathology ; Mice ; Mice, Inbred BALB C ; Spleen/*physiology ; Splenectomy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Prolongation of islet xenograft survival without continuous immunosuppression (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-07-11
    Description: The survival of isolated rat islets transplanted into diabetic mice was prolonged markedly by maintaining the rat islets in vitro at 24 degrees C for 7 days before transplantation and administering to the recipients a single injection of antiserum to mouse and rat lymphocytes shortly before transplantation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lacy, P E -- Davie, J M -- Finke, E H -- New York, N.Y. -- Science. 1980 Jul 11;209(4453):283-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6770465" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/analysis ; Cell Survival ; Cells, Cultured ; Diabetes Mellitus, Experimental/*therapy ; *Immunosuppression ; *Islets of Langerhans Transplantation ; Lymphocytes/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Rats ; Transplantation, Heterologous ; Transplantation, Isogeneic
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Phenacetin safety (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macklin, A W -- Welch, R M -- New York, N.Y. -- Science. 1980 Jan 11;207(4427):129-30, 132.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7350647" target="_blank"〉PubMed〈/a〉
    Keywords: Aminopyrine/adverse effects/toxicity ; Animals ; Humans ; Mice ; Mutagens ; Phenacetin/administration & dosage/*adverse effects/toxicity ; Rats
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Immunoglobulin gene rearrangement in immature B cells (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-09-19
    Description: Two types of immature B cells, namely fetal liver hybridomas and the leukemic cell line 70Z/3, both of which have cytoplasmic mu chains but no light chains, were examined for DNA rearrangements of their light chain and heavy chain immunoglobulin genes. In the fetal liver hybridomas, which were constructed from fetal liver cells and a tumor cell, no light chain gene rearrangement was observed, whereas in the 70Z/3 cell line a kappa light chain rearrangement probably occurred. The results suggest that, although the lack of light chain synthesis can be due to a lack of gene rearrangement, there may also be transcriptional regulation, which may also be important for the expression of light chain immunoglobulins in immature B cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maki, R -- Kearney, J -- Paige, C -- Tonegawa, S -- New York, N.Y. -- Science. 1980 Sep 19;209(4463):1366-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6774416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*immunology ; Genes ; Hybrid Cells/immunology ; Immunoglobulin Constant Regions/genetics ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Light Chains/*genetics ; Immunoglobulin Variable Region/genetics ; Immunoglobulin kappa-Chains/*genetics ; Immunoglobulin mu-Chains/*genetics ; Leukemia, Experimental/*immunology ; Liver/*embryology ; Mice ; Recombination, Genetic ; Transcription, Genetic
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Mapping of heavy chain genes for mouse immunoglobulins M and D (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-09-19
    Description: A single DNA fragment containing both mu and delta immunoglobulin heavy chain genes has been cloned from normal BALB/c mouse liver DNA with a new lambda phage vector Charon 28. The physical distance between the membrane terminal exon of mu and the first domain of delta is 2466 base pairs, with delta on the 3' side of mu. A single transcript could contain a variable region and both mu and delta constant regions. The dual expression of immunoglobulins M and D on spleen B cells may be due to alternate splicing of this transcript.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, C P -- Tucker, P W -- Mushinski, J F -- Blattner, F R -- New York, N.Y. -- Science. 1980 Sep 19;209(4463):1348-53.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6774414" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/immunology ; Chromosome Deletion ; *Genes ; Immunoglobulin Constant Regions/genetics ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin delta-Chains/*genetics ; Immunoglobulin mu-Chains/*genetics ; Liver/physiology ; Membrane Proteins/genetics ; Mice ; Myeloma Proteins/genetics ; Plasmids ; RNA, Messenger/genetics ; Recombination, Genetic
    Print ISSN: 0036-8075
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    Selective inhibition of glycoprotein and membrane protein of vesicular stomatitis virus from interferon-treated cells (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-02-01
    Description: A 200-fold inhibition in the titer of infectious vesicular stomatitis virus (VSV) was produced in cultures of Ly cells treated with 30 reference units of interferon per milliliter. Virus particle production, as measured by VSV particle-associated transcriptase, or nucleocapsid protein was inhibited by a maximum of tenfold. The glycoprotein and membrane protein content was reduced in VSV derived from interferon-treated cells. Thus interferon-treated cells may have produced VSV particles with low infectivity, which may be related to the reduced amount of glycoprotein incorporated into such particles. These findings resemble those reported in interferon-treated cells infected with murine leukemia viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maheshwari, R K -- Jay, F T -- Friedman, R M -- New York, N.Y. -- Science. 1980 Feb 1;207(4430):540-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6243416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Defective Viruses/growth & development ; Glycoproteins/*biosynthesis ; Interferons/*pharmacology ; Membrane Proteins/*biosynthesis ; Mice ; RNA, Viral/metabolism ; Vesicular stomatitis Indiana virus/*growth & development ; Viral Proteins/*biosynthesis ; Virus Replication/*drug effects
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    (-)Pentobarbital opens ion channels of long duration in cultured mouse spinal neurons (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-07-25
    Description: Intracellular recordings from voltage-clamped mouse spinal neurons in tissue culture were used to study the membrane mechanisms underlying inhibitory responses to gamma-aminobutyric acid and the (-) isomer of pentobarbital. Fluctuation analysis suggested that both substances activated ion channels in the membranes. However, the channels activated by pentobarbital remained open five times longer than those activated by gamma-aminobutyric acid.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathers, D A -- Barker, J L -- New York, N.Y. -- Science. 1980 Jul 25;209(4455):507-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6248961" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/drug effects/physiology ; Cells, Cultured ; Ion Channels/drug effects/*physiology ; Membrane Potentials/drug effects ; Mice ; Neurons/drug effects/*physiology ; Pentobarbital/*pharmacology ; Spinal Cord/*physiology ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Vesicle targeting: timed release and specificity for leukocytes in mice by subcutaneous injection (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-01-18
    Description: When unilamellar vesicles were administered subcutaneously in mice, the half-time for the destruction of the vesicles varied from 12 to 600 hours, depending on their composition. The vesicles tested consisted of distearoyl phosphatidylcholine, cholesterol, and certain sugar and amino-sugar derivatives of cholesterol. Vesicle with amino-sugar derivatives showed the greatest longevity and became localized with high specificity in aggregates of polymorphonuclear leukocytes. A substantial delay between the time that the vesicles broke open and the time that labels contained in the vesicles were excreted suggests that the vesicles undergo endocytosis before destruction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mauk, M R -- Gamble, R C -- Baldeschwieler, J D -- New York, N.Y. -- Science. 1980 Jan 18;207(4428):309-11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7350660" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cholesterol/analogs & derivatives ; Endocytosis ; Liposomes/*therapeutic use ; Lysosomes/metabolism ; Metabolic Clearance Rate ; Mice ; Neutrophils/*metabolism ; Phosphatidylcholines ; Structure-Activity Relationship
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  • 73
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    Mebendazole therapy of parenteral trichinellosis (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-03-14
    Description: Mebendazole was highly effective against the helminth parasite Trichinella spiralis in mice subjected to a 3-day course of treatment during the invasive and encystment phases of experimental trichinellosis. When treatment began either 2 or 4 weeks after the mice were inoculated with parasites, the number of larvae developing in the host musculature was greatly reduced by twice-daily oral administration of 3.125, 6.25, or 12.5 milligrams of mebendazole per kilogram of body weight.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCracken, R O -- Taylor, D D -- New York, N.Y. -- Science. 1980 Mar 14;207(4436):1220-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7355285" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Animals ; Benzimidazoles/*therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Larva ; Male ; Mebendazole/administration & dosage/*therapeutic use ; Mice ; Muscles/parasitology ; Trichinella/drug effects ; Trichinellosis/*drug therapy
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  • 74
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    Insertion of a new gene of viral origin into bone marrow cells of mice (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-05-30
    Description: DNA containing the herpes simplex virus thymidine kinase (HSVtk) gene was used to transform wild-type tk+ mouse L cells to a tk++ status in vitro using methotrexate as a selective agent. HSVtk DNA was also used to transform mouse bone marrow cells in vitro. Transformed marrow cells injected into irradiated and methotrexate-treated recipient mice gave rise to proliferating cells which in some cases dominated the marrow population and which contained HSVtk gene sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mercola, K E -- Stang, H D -- Browne, J -- Salser, W -- Cline, M J -- New York, N.Y. -- Science. 1980 May 30;208(4447):1033-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6246577" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow/*enzymology ; Bone Marrow Transplantation ; DNA, Viral/analysis ; Drug Resistance ; *Genes, Viral ; L Cells (Cell Line) ; Methotrexate/pharmacology ; Mice ; Simplexvirus/enzymology/*genetics ; Species Specificity ; Thymidine Kinase/*genetics ; *Transformation, Genetic
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  • 75
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    J genes for heavy chain immunoglobulins of mouse (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-09-05
    Description: A 15,8-kilobase pair fragment of BALB/c mouse liver DNA, cloned in the Charon 4A lambda phage vector system, was shown to contain the mu heavy chain constant region (CHmu) gene for the mouse immunoglobulin M. In addition, this fragment of DNA contains at least two J genes, used to code for the carboxyl terminal portion of heavy chain variable regions. These genes are located in genomic DNA about eight kilobase pairs to the 5' side of the CHmu gene. The complete nucleotide sequence of a 1120-base pair stretch of DNA that includes the two J genes has been determined.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newell, N -- Richards, J E -- Tucker, P W -- Blattner, F R -- New York, N.Y. -- Science. 1980 Sep 5;209(4461):1128-32.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6250219" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites, Antibody/*genetics ; DNA Restriction Enzymes ; DNA, Recombinant ; Genes ; Genetic Linkage ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Variable Region/*genetics ; Immunoglobulin mu-Chains/*genetics ; Mice
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  • 76
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    Gene affecting superoxide dismutase activity linked to the histocompatibility complex in H-2 congenic mice (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-01-04
    Description: The activity of cyanide-sensitive, Cu-Zn superoxide dismutase (SOD) was studied in liver sytosols from H-2 congenic strains of mice. Higher SOD activity was found in livers of mice having H-2b/A.BY, B10, and C3H.SW/haplotypes than in those of H-2a, H-2k and H-2d haplotypes. Segregation studies supported these correlations. In H-2 recombinant strains of mice, the genes influencing the liver SOD activity occur, as ascertained by mapping techniques, at or near the H-2d region of the major histocompatibility complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Novak, R -- Bosze, Z -- Matkovics, B -- Fachet, J -- New York, N.Y. -- Science. 1980 Jan 4;207(4426):86-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7350646" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Genes ; Genes, Regulator ; Genetic Linkage ; H-2 Antigens/*genetics ; Liver/enzymology ; *Major Histocompatibility Complex ; Mice ; Superoxide Dismutase/*genetics
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  • 77
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    Substance P: does it produce analgesia or hyperalgesia? (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-04-18
    Description: In the hot plate test, substance P given intravenously at doses of 5 x 10-5 and 5 x 10-4 gram per kilogram caused analgesia, while lower doses caused hyperalgesia. The influence of substance P on nociception depended on the individual mouse's sensitivity to pain (control response latency). Analgesia was produced by substance P administered to mice with high sensitivity to thermic stimulation, whereas hyperalgesia occurred in mice whose control latencies were longer than normal. This result is interpreted as an indication that substance P is capable of normalizing responsiveness to pain and could be classified as a regulatory peptide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oehme, P -- Hilse, H -- Morgenstern, E -- Gores, E -- New York, N.Y. -- Science. 1980 Apr 18;208(4441):305-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6154313" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates ; Animals ; Dose-Response Relationship, Drug ; Hot Temperature ; Hyperalgesia/*chemically induced ; Hyperesthesia/*chemically induced ; Mice ; Nociceptors/drug effects ; Pain/*physiopathology ; Perception/*drug effects ; Receptors, Drug/physiology ; Substance P/*pharmacology
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  • 78
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    Human monoclonal antibody against Forssman antigen (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-10-31
    Description: Hybrid cells formed between human lymphocytes and mouse myeloma cells produce human immunoglobulin in culture. Stable antibody-producing cell lines can be isolated after multiple cycles of low-density passage, cloning, and continued selection for immunoglobulin production. The origin and characteristics of a hybrid of human and mouse cells is described. This hybrid produces high concentrations (8.3 micrograms per milliliter) of human immunoglobulin M reactive with the terminal disaccharide of the Forssman glycolipid. These findings point to the potential use of human-mouse hybrid cells as a source of human monoclonal antibodies for therapeutic and diagnostic purposes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nowinski, R -- Berglund, C -- Lane, J -- Lostrom, M -- Bernstein, I -- Young, W -- Hakomori, S I -- Hill, L -- Cooney, M -- New York, N.Y. -- Science. 1980 Oct 31;210(4469):537-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7423202" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antibodies ; Antibody Formation ; Antibody Specificity ; Cells, Cultured ; Clone Cells/immunology ; *Forssman Antigen ; Humans ; Hybrid Cells/immunology ; Immunoglobulin M/biosynthesis ; Mice
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  • 79
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    alpha-Lactalbumin-casein induction in virgin mouse mammary explants: dose-dependent differential action of cortisol (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-03-21
    Description: The interplay of insulin, cortisol, and prolactin induces synthesis of casein and alpha-lactalbumin in cultured mammary explants from mature virgin mice. A striking difference has been found between the optimal concentrations of cortisol required for maximal induction of the two milk proteins in vitro: 3 x 10(-8) molar for alpha-lactalbumin and 3 x 10(-6) molar for casein. Moreover, 10(-7) to 10(-5) molar cortisol caused progressive inhibition of alpha-lactalbumin accumulation. Such differential actions of cortisol may partly account for the asynchronous synthesis of the two proteins during pregnancy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ono, M -- Oka, T -- New York, N.Y. -- Science. 1980 Mar 21;207(4437):1367-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6986657" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caseins/*biosynthesis ; Dose-Response Relationship, Drug ; Drug Interactions ; Female ; Hydrocortisone/*pharmacology ; Insulin/pharmacology ; Lactalbumin/*biosynthesis ; Mammary Glands, Animal/drug effects/*metabolism ; Mice ; Organ Culture Techniques ; Pregnancy ; Prolactin/pharmacology
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  • 80
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    Properties of a normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney sarcoma virus (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-03-14
    Description: A 15.0-kilobase (kb) Eco RI DNA fragment from normal mouse Balb/c genomic DNA that contains sequences (sarc) homologous to the acquired cell sequences (src) of Moloney sarcoma virus (MSV) has been cloned in phage lambda. The sarc region (1.2 to 1.3 kb) of the 15.0-kb cell fragment is indistinguishable from the src region of two isolates of MSV as judged by heteroduplex and restriction endonuclease analyses. The cellular sequences flanking sarc show no homology to other MSV sequences. Whereas cloned subgenomic portions of MSV that contain src transformed NIH-3T3 cells in vitro, the cloned sarc fragment is inactive.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oskarsson, M -- McClements, W L -- Blair, D G -- Maizel, J V -- Vande Woude, G F -- New York, N.Y. -- Science. 1980 Mar 14;207(4436):1222-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6243788" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosome Mapping ; DNA Restriction Enzymes ; *Genes ; *Genes, Viral ; Mice ; Mice, Inbred BALB C/*genetics ; Moloney murine leukemia virus/*genetics ; Nucleic Acid Hybridization
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  • 81
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    Cytosolic and microsomal epoxide hydrolases: differential properties in mammalian liver (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-03-28
    Description: The epoxide hydrolase activities of the 100,000 g pellet (microsomal) and 100,00 g soluble (cystosolic) fractions of mouse, rat, and guinea pig liver were measured with three closely related compounds used as substrates. Differences between the species in the distribution of the cytosolic and microsomal hydrolases and in their substrate specificities and pH optima demonstrate why epoxide hydrolase activity in the cytosolic fraction was not detected earlier in spie of intensive work on the microsomal epoxide hydrolase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ota, K -- Hammock, B D -- New York, N.Y. -- Science. 1980 Mar 28;207(4438):1479-81.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7361100" target="_blank"〉PubMed〈/a〉
    Keywords: Allyl Compounds ; Animals ; Benzene ; Cytosol/enzymology ; Epoxide Hydrolases/*metabolism ; Guinea Pigs ; Hydrogen-Ion Concentration ; Liver/*enzymology/ultrastructure ; Mice ; Microsomes, Liver/enzymology ; Rats ; Styrenes ; Substrate Specificity
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  • 82
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    Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-07-11
    Description: The human genes for growth hormone (GH), chorionic somatomammotropin (CSH), and a third growth hormone-like gene (GHL) have been located on chromosome 17 in humans. DNA fragments of 2.6, 2.8, and 9.5 kilobase pairs containing GH, CSH, and GHL, respectively, were identified in human genomic DNA, and a 7.5-kilobase DNA fragment related to growth hormone DNA sequences was found in mouse cells. In somatic hybrids of human and mouse cells containing reduced numbers of human chromosomes, but a normal complement of mouse chromosomes, the mouse, 7.5-kolobase DNA fragment was always present, whereas the 2.6-, 2.8-, and 9.5-kilobase human fragments were present only when human chromosome 17 was also present.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Owerbach, D -- Rutter, W J -- Martial, J A -- Baxter, J D -- Shows, T B -- New York, N.Y. -- Science. 1980 Jul 11;209(4453):289-92.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7384802" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; *Chromosomes, Human, 16-18 ; *DNA/metabolism ; *Genes ; Growth Hormone/*biosynthesis ; Humans ; Hybrid Cells/metabolism ; Mice ; Placental Lactogen/*biosynthesis ; Translocation, Genetic
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  • 83
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    Opiate analgesia: evidence for mediation by a subpopulation of opiate receptors (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-05-02
    Description: Naloxazone, a hydrazone derivative of the opiate antagonist naloxone, has a high affinity for opiate receptor binding sites. Naloxazone injections reduce opiate receptor binding to extensively washed mouse brain membranes for more than 24 hours, suggesting that the effect is irreversible. High-affinity binding sites are abolished by this treatment, whereas low-affinity sites are unaffected. Naloxazone treatment blocks the analgesic effects of morphine for at least 24 hours but does not prevent death from high doses of morphine. Thus analgesic but nonlethal opiate effects may be mediated by the high-affinity subpopulation of opiate receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pasternak, G W -- Childers, S R -- Snyder, S H -- New York, N.Y. -- Science. 1980 May 2;208(4443):514-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6245448" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites/drug effects ; Brain/metabolism ; Mice ; Morphine/pharmacology/toxicity ; Naloxone/adverse effects/*analogs & derivatives/pharmacology ; Receptors, Opioid/classification/*drug effects/physiology
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  • 84
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    Estrogen and the growth of breast cancer: new evidence suggests indirect action (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-08-08
    Description: The growth of the MCF-7 human breast cancer cell line is unresponsive to the presence of estrogen in culture media. Paradoxically, in nude mice, growth of these cells and formation of solid tumors are dependent on estrogen. Tumors fail to develop in ovariectomized mice, but do develop in intact mice and in ovariectomized mice given estrogen. Primary cultures derived from MCF-7 tumors revert to unresponsiveness to estrogen. However, when these cultures are again transplanted into nude mice, estrogen is required for tumor formation. The continuous culture, the solid tumor, and the primary cultures therefrom have similar estrogen-binding capacities and affinities. These results indicate that mammary carcinoma cell growth in vivo is subject to inhibition that can be overcome by estrogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shafie, S M -- New York, N.Y. -- Science. 1980 Aug 8;209(4457):701-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6994231" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/metabolism/*physiopathology ; Castration ; Cell Division/drug effects ; Cell Line ; Cytosol/metabolism ; Estradiol/metabolism/*pharmacology ; Female ; Humans ; Insulin/pharmacology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Receptors, Estrogen/metabolism ; Transplantation, Heterologous
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  • 85
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    Correction of enzyme deficiency in mice by allogeneic bone marrow transplantation with total lymphoid irradiation (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-12-05
    Description: Enzyme deficiency was corrected in mice after allogeneic bone marrow transplantation with occurrence of graft versus host disease. beta-Glucuronidase-deficient C3H/HeJ mice were treated with total lymphoid irradiation. Normal bone marrow cells (30 X 10(6)) from BALB/c to C3H/HeJ chimeras (〉90 percent circulating donor-type cells) without graft versus host disease. beta-Glucuronidase activity increases to normal levels in all chimeras as measured in the liver and in the plasma. Activity was maintained throughout an observation period of 7 months.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slavin, S -- Yatziv, S -- A1 15387/PHS HHS/ -- New York, N.Y. -- Science. 1980 Dec 5;210(4474):1150-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7003711" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bone Marrow Transplantation ; Glucuronidase/blood/*deficiency ; Liver/enzymology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Radiation Chimera ; Transplantation, Homologous
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  • 86
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    Neurobiology of amnesia (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-08-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Squire, L R -- Davis, H P -- Spanis, C W -- New York, N.Y. -- Science. 1980 Aug 15;209(4458):836-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7190729" target="_blank"〉PubMed〈/a〉
    Keywords: Amnesia/*physiopathology ; Amnesia, Retrograde/*physiopathology ; Animals ; Brain Chemistry ; Catecholamines/metabolism ; Cycloheximide/pharmacology ; Humans ; Memory/drug effects ; Mice ; Nerve Tissue Proteins/biosynthesis ; Phenoxybenzamine/pharmacology
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  • 87
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    Glucan-induced modification of murine viral hepatitis (1980)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 1980-04-04
    Description: Glucan, a macrophage stimulant, was evaluated for its ability to alter survival and phagocytic dysfunction in mice challenged with mouse hepatitis virus strain MHV-A59. Administration of glucan before the mice were challenged with the virus significantly prolonged median survival time but did not modify overall mortality compared with control mice given dextrose. Maximal effectiveness was achieved when glucan was administered both before and after the viral challenge. In contrast to the marked hepatic parenchymal cell necrosis observed in the control mice, glucan-treated mice exhibited reduced pathology. Intraperitoneal administration of MHV-A59 resulted in a significant depression of phagocytic activity compared with controls that were not exposed to the virus. The enhancement in phagocytic function in glucan-treated control mice was unaltered in virus-challenged, glucan-treated mice. Thus glucan is capable of increasing survival, inhibiting hepatic necrosis, and maintaining an activated state of phagocytic activity in mice challenged with MHV-A59. Macrophage stimulants may have a significant role in the modification of virally induced hepatic lesions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, D L -- Di Luzio, N R -- New York, N.Y. -- Science. 1980 Apr 4;208(4439):67-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7361108" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Glucans/*pharmacology/therapeutic use ; Hepatitis, Viral, Animal/drug therapy/*immunology/mortality ; Liver/pathology ; Macrophages/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Phagocytosis/*drug effects
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  • 88
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    Latency of herpes simplex virus in absence of neutralizing antibody: model for reactivation (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-11-28
    Description: Mice inoculated with herpes simplex virus (type 1) by the lip or corneal route and then passively immunized with rabbit antibody to herpes simplex virus developed a latent infection in the trigeminal ganglia within 96 hours. Neutralizing antibody to herpes simplex virus was cleared from the circulation and could not be detected in most of these mice after 2 months. Examination of ganglia from the antibody-negative mice revealed latent virus in over 90 percent of the animals, indicating that serum neutralizing antibody is not necessary to maintain the latent state. When the lips or corneas of these mice were traumatized, viral reactivation occurred in up to 90 percent of the mice, as demonstrated by the appearance of neutralizing antibody. This study provides a model for identifying factors that trigger viral reactivation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sekizawa, T -- Openshaw, H -- Wohlenberg, C -- Notkins, A L -- New York, N.Y. -- Science. 1980 Nov 28;210(4473):1026-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6254149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/*metabolism ; Antigens, Viral/analysis ; Disease Models, Animal ; Ganglia/microbiology ; Herpes Simplex/*immunology ; Immune Tolerance ; Immunization, Passive ; Mice ; Simplexvirus/*growth & development/immunology ; *Virus Activation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 89
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    Hemoglobin switching: a cellular model (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-02-08
    Description: Regulation of hemoglobin synthesis depends in part on the population of cells available for erythroid differentiation. Mouse erythroleukemia cells were cloned, and the clones were induced with dimethyl sulfoxide to test the relative induction of beta minor and beta major synthesis. Cells of line 745 produced approximately 35 percent beta minor after induction, and 39 clones of line 745 produced from 23 to 61 percent beta minor. Further subcloning of the clone that produced 61 percent beta minor led to three subclones, all of which produced more than 90 percent beta minor. Thus one kind of hemoglobin regulation occurs at the cellular level.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alter, B P -- Goff, S C -- New York, N.Y. -- Science. 1980 Feb 8;207(4431):647-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6928071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Line ; Clone Cells/metabolism ; Dimethyl Sulfoxide/pharmacology ; Globins/*biosynthesis/genetics ; Leukemia, Erythroblastic, Acute/metabolism ; Mice
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 90
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    Polyamine metabolism: a potential therapeutic target in trypanosomes (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-10-17
    Description: alpha-Difluoromethylornithine (RMI 71,782), a specific irreversible inhibitor of the first step in polyamine biosynthesis, that is, the formation of putrescine from ornithine by ornithine decarboxylase, cures mice infected with a virulent, rodent-passaged strain of Trypanosoma brucei brucei. This parasite is closely related to the trypanosomes that cause human sleeping sickness. The drug, which is remarkably nontoxic, was effective when administered in drinking water or by intubation. The ability of the compound to inhibit ornithine decarboxylase in vitro was demonstrated by the reduced amounts of putrescine synthesized from tritiated ornithine in Trypanosoma brucei suspensions. These observations direct attention to polyamine metabolism as a target for chemotherapy of parasitic diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bacchi, C J -- Nathan, H C -- Hutner, S H -- McCann, P P -- Sjoerdsma, A -- AI 13801/AI/NIAID NIH HHS/ -- AI 13852/AI/NIAID NIH HHS/ -- FR-05596/PHS HHS/ -- New York, N.Y. -- Science. 1980 Oct 17;210(4467):332-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6775372" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Eflornithine ; Mice ; Ornithine/analogs & derivatives/metabolism/pharmacology ; Ornithine Decarboxylase Inhibitors ; Polyamines/*metabolism ; *Trypanocidal Agents ; Trypanosoma brucei brucei/drug effects/metabolism ; Trypanosomiasis, African/*drug therapy
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  • 91
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    Picrotoxin convulsions involve synaptic and nonsynaptic mechanisms on cultured mouse spinal neurons (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-05-30
    Description: The cellular mechanisms underlying picrotoxin-induced convulsive activity were studied by using mouse spinal neurons growing in tissue culture. Picrotoxin-induced convulsive activity in most but not all of the cells studied. The activity could be inverted by polarizing to positive potentials and eliminated either by decreasing the ratio of calcium to magnesium or by applying tetrodotoxin. When applied locally to individual cells, picrotoxin lowered spike threshold and induced spontaneous firing in some but not all cells tested. The results suggest that picrotoxin-induced convulsive activity involves rapidly summating synaptic activity which may be evoked by high-frequency repetitive firing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barker, J L -- MacDonald, J F -- New York, N.Y. -- Science. 1980 May 30;208(4447):1054-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7375918" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Animals ; Calcium/pharmacology ; Cells, Cultured ; Magnesium/pharmacology ; Membrane Potentials/drug effects ; Mice ; Picrotoxin/*pharmacology ; Seizures/*chemically induced ; Spinal Cord/*drug effects/physiology ; Synapses/*drug effects
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 92
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    Age-related changes in passive avoidance retention: modulation with dietary choline (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bartus, R T -- Dean, R L -- Goas, J A -- Lippa, A S -- New York, N.Y. -- Science. 1980 Jul 11;209(4453):301-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7384805" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Aging ; Animals ; Avoidance Learning/*drug effects ; Choline/administration & dosage/*pharmacology ; Mice ; Mice, Inbred Strains ; Time Factors
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  • 93
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    Mouse leukemia: therapy with monoclonal antibodies against a thymus differentiation antigen (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-01-04
    Description: Monoclonal antibodies against a thymus cell differentiation antigen (Thy-1.1) were effective in the therapy of a transplanted mouse leukemia. Passive immunization resulted in high titers of cytotoxic antibody in the serum of treated mice and the suppression of metastatic tumor cells. The tumor-suppressive effects of the monoclonal antibodies were amplified by the administration of exogenous complement. This combined antibody and complement therapy resulted in the cure of leukemia in a significant proportion of the treated animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, I D -- Tam, M R -- Nowinski, R C -- New York, N.Y. -- Science. 1980 Jan 4;207(4426):68-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6965328" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Specificity ; Antigens, Surface ; Antilymphocyte Serum/*therapeutic use ; Cell Differentiation ; Clone Cells/immunology ; Cytotoxicity, Immunologic ; Immunotherapy ; Leukemia, Experimental/surgery/*therapy ; Mice ; Mice, Inbred Strains ; Neoplasm Metastasis ; T-Lymphocytes/*immunology
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  • 94
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    Limitations of metabolic activation systems used with in vitro tests for carcinogens (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-07-25
    Description: Important differences between the metabolic activation of 7,12-dimethylbenz[a]anthracene in intact cellular systems and in liver homogenates suggest that the use of homogenates in conjunction with short-term assays for carcinogens could yield misleading results.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bigger, C A -- Tomaszewski, J E -- Dipple, A -- Lake, R S -- New York, N.Y. -- Science. 1980 Jul 25;209(4455):503-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6771871" target="_blank"〉PubMed〈/a〉
    Keywords: 9,10-Dimethyl-1,2-benzanthracene/*metabolism ; Animals ; Benz(a)Anthracenes/*metabolism ; Carcinogens/*metabolism ; Cells, Cultured ; DNA/metabolism ; Deoxyribonucleosides ; Drug Evaluation, Preclinical/methods ; Humans ; Liver/*metabolism ; Mice ; Microsomes, Liver/metabolism ; Rats ; Skin/metabolism
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  • 95
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    Electrophoretic injection of a fluorescent dye into giant mitochondria and mitoplasts (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-09-12
    Description: Studies of the electrical properties of giant mitochondria and mitoplasts with microelectrodes have indicated that there are no significant metabolically dependent membrane potentials. The internal location of the microelectrode has been confirmed by electrophoretically microinjecting the water-soluble dye Lucifer yellow CH into giant mitochondria or mitoplasts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowman, C -- Tedeschi, H -- New York, N.Y. -- Science. 1980 Sep 12;209(4462):1251-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7403882" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electrophoresis ; Fluorescent Dyes/*administration & dosage ; Membrane Potentials ; Mice ; Microelectrodes ; Mitochondria, Liver/*physiology/ultrastructure
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  • 96
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    Histamine-mediated delayed permeability response after scald burn inhibited by cimetidine or cold-water treatment (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-08-15
    Description: Scald injury to one ear of the hairless mouse induced significant (P 〈 .05) delayed edema formation in remote, uninjured skin. This remote edema formation was completely inhibited by immediate cold-water treatment of the scalded ear. Cold-water treatment significantly reduced histamine loss from the scalded ear, and the edema-inhibiting effect of the treatment could be mimicked by treating the animal prior to injury with the H2-histamine receptor antagonist cimetidine or a drug that causes histamine depletion. These observations suggest (i) that a histamine-mediated, delayed permeability response occurs after thermal injury that causes remote edema formation and (ii) that one mechanism of remote edema inhibition by cold-water treatment is the prevention of histamine release from thermally injured tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boykin, J V Jr -- Eriksson, E -- Sholley, M M -- Pittman, R N -- New York, N.Y. -- Science. 1980 Aug 15;209(4458):815-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6157189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Burns/complications/physiopathology/*therapy ; Cell Membrane Permeability ; Cimetidine/*pharmacology ; *Cold Temperature ; Edema/etiology/physiopathology ; Guanidines/*pharmacology ; Histamine Release/*drug effects ; Indomethacin/pharmacology ; Male ; Mice ; Receptors, Histamine H2/physiology
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  • 97
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    Inhibition of cell motility by interferon (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-05-02
    Description: Interferon derived from human leukocytes, human fibroblasts, and mouse fibroblasts was found to inhibit the motility of cultured cells. It inhibits the tumor-induced motility of capillary endothelial cells as well as the spontaneous migration of other cell types. The ability of a given preparation of interferon to inhibit the motility of a given cell type is proportional to its antiviral activity in that particular cell type. Antiserum to human leukocyte interferon neutralizes both the motility-inhibitory activity and the antiviral activity of this preparation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brouty-Boye, D -- Zetter, B R -- New York, N.Y. -- Science. 1980 May 2;208(4443):516-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6154315" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antineoplastic Agents ; Antiviral Agents ; Capillaries/cytology ; Cattle ; *Cell Movement ; Cells, Cultured/physiology ; Endothelium/cytology ; Fibroblasts ; Humans ; Interferons/*pharmacology ; Leukocytes/physiology ; Mice ; Neoplasms/pathology
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  • 98
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    gamma-Glutamyl transpeptidase in isolated brain endothelial cells: induction by glial cells in vitro (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-02-08
    Description: The endothelia of microvessels isolated from mouse brain by mechanical means are rich in gamma-glutamyl transpeptidase; however, the enzyme often disappears when the cells migrate or proliferate from the microvessel isolates. In an endothelial cell line derived from similar isolates and negative for gamma-glutamyl transpeptidase, the enzyme could be induced in the endothelial cells when they were cocultured with glial cells. Thus there may be a requirement for continuous induction of gamma-glutamyl transpeptidase in brain microvessels by adjacent glial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeBault, L E -- Cancilla, P A -- New York, N.Y. -- Science. 1980 Feb 8;207(4431):653-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6101511" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*blood supply ; Capillaries/*enzymology ; Cells, Cultured ; Endothelium/enzymology ; Enzyme Induction ; Glioma/physiopathology ; Mice ; Neuroglia/*physiology ; Rats ; gamma-Glutamyltransferase/*biosynthesis
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  • 99
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    Epidermal growth factor is a major growth-promoting agent in human milk (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-10-10
    Description: Human milk stimulates DNA synthesis in cell cultures in which growth has been arrested. The mitogenic activity of milk is neutralized by the addition of antibody to human epidermal growth factor. The results identify epidermal growth factor as a major growth-promoting agent in breast milk.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carpenter, G -- CA24071/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1980 Oct 10;210(4466):198-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6968093" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division/drug effects ; Cells, Cultured ; DNA/biosynthesis ; Epidermal Growth Factor/analysis/*pharmacology ; Female ; Humans ; Mice ; Milk, Human/analysis/*physiology ; Mitogens ; Peptides/*pharmacology
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  • 100
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    Postsynaptic transmission block can cause terminal sprouting of a motor nerve (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-02-08
    Description: Sprouting of mouse soleus motor nerve terminals can be evoked by daily intramuscular injections of purified alpha-bungarotoxin. This finding supports the hypothesis that an important stimulus to terminal sprouting in partial denervation and presynaptic nerve blockade is a product of inactive muscle fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holland, R L -- Brown, M C -- New York, N.Y. -- Science. 1980 Feb 8;207(4431):649-51.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6243417" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Botulinum Toxins/pharmacology ; Bungarotoxins/*pharmacology ; Female ; Mice ; Motor Endplate/drug effects ; Motor Neurons/*growth & development ; Muscles/innervation ; Neuromuscular Junction/*physiology ; Receptors, Cholinergic/drug effects ; Synaptic Transmission/*drug effects
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