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  • 1980-1984  (712)
  • 1980  (712)
  • Cell & Developmental Biology  (654)
  • pharmacokinetics
  • Nuclear reactions
  • 1
    Electronic Resource
    Electronic Resource
    Metabolic effects and pharmacokinetics of intravenously administered dichloroacetate in humans (1980)
    Springer
    Diabetologia 19 (1980), S. 109-113 
    Details
    ISSN: 1432-0428
    Keywords: Dichloroacetate ; pharmacokinetics ; lactate ; lactic acidosis ; alanine ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1–50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p〈0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 μg/ml, elimination was monoexponential with a half-life of 32±11 min (mean±SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421855
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  • 2
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561675
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  • 3
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562615
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  • 4
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558453
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  • 5
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561393
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  • 6
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561395
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  • 7
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561899
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  • 8
    Electronic Resource
    Electronic Resource
    Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561903
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  • 9
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625801
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  • 10
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of microcrystalline theophylline (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558452
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  • 11
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570159
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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
    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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  • 14
    Electronic Resource
    Electronic Resource
    Placental transfer of pethidine and norpethidine and their pharmacokinetics in the newborn (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561475
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  • 15
    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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  • 16
    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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  • 17
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and dosage of digoxin in neonates and infants (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561481
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  • 18
    Electronic Resource
    Electronic Resource
    Effectiveness and pharmacokinetics of indomethacin in premature newborns with patent ductus arteriosus (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561483
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  • 19
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561487
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  • 20
    Electronic Resource
    Electronic Resource
    Nortriptyline therapy in elderly patients: Dosage prediction after single dose pharmacokinetic study (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561582
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  • 21
    Electronic Resource
    Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561586
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  • 22
    Electronic Resource
    Electronic Resource
    Effect of posture and sleep on pharmacokinetics (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561587
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  • 23
    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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  • 24
    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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  • 25
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636794
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  • 26
    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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  • 27
    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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  • 28
    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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  • 29
    Electronic Resource
    Electronic Resource
    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 
    Details
    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).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558443
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  • 30
    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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  • 31
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636787
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  • 32
    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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  • 33
    Electronic Resource
    Electronic Resource
    Influence of dose on the pharmacokinetics of Cefadroxil (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874664
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  • 34
    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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  • 35
    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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  • 36
    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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  • 37
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    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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  • 38
    Electronic Resource
    Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561902
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  • 39
    Electronic Resource
    Electronic Resource
    Comparative in vitro effects and in vivo kinetics of antithyroid drugs (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625803
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  • 40
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558446
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  • 41
    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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  • 42
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563009
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  • 43
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563012
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  • 44
    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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  • 45
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636789
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  • 46
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636790
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  • 47
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of intravenously administered bumetanide in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059643
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  • 48
    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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  • 49
    Electronic Resource
    Electronic Resource
    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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  • 50
    Electronic Resource
    Electronic Resource
    Influence of renal failure on the hepatic clearance of bufuralol in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059544
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  • 51
    Electronic Resource
    Electronic Resource
    Symbols in pharmacokinetics (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 497-507 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059548
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  • 52
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    Electronic Resource
    Identifiable pharmacokinetic models: The role of extra inputs and measurements (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060058
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  • 53
    Electronic Resource
    Electronic Resource
    Melatonin administration to dogs (1980)
    Springer
    Journal of neural transmission 49 (1980), S. 281-285 
    Details
    ISSN: 1435-1463
    Keywords: Melatonin administration ; diurnal rhythm ; dog ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Melatonin concentrations in serum and urine were examined following oral administration of melatonin to dogs. Four different doses of melatonin ranging from 10 to 80 mg per kg of body weight were given. Melatonin was rapidly absorbed and reached a maximum serum level after 20–30 min, with a distribution phase of 3.5 hours and elimination half life (t1/2) of 5 hours. The fraction excreted in the urine was 0.25% of the administrated dose during the first 5 hours. These results as well as the diurnal rhythm of serum melatonin in the dog are similar to corresponding data reported in the human.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01252131
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  • 54
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    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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  • 55
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    Electronic Resource
    Use of an (n, α) nuclear reaction to study the long-distance transport of boron in trifolium repens after foliar application (1980)
    Springer
    Planta 150 (1980), S. 197-205 
    Details
    ISSN: 1432-2048
    Keywords: Boron ; Foliar nutrition ; Nuclear reactions ; Transport (boron) ; Trifolium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The growth of white clover (Trifolium repens L.) is severely inhibited by boron starvation, but a foliar treatment with boric acid can transitorily alleviate the deficiency symptoms. The 10B(n ,α)7 Li nuclear reaction has been used to study boron transport in the plant after foliar application. More than 98% of the boron supplied remained at the point where it was applied to the leaves, and less than 2% was useful to the growth of the treated plant. This small “efficient” portion of boron was quite mobile. It was distributed to the different parts of the plant, then was transferred from the oldest parts to the newly formed leaves. Physiological and agronomical implications of these data are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00390826
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980) 
    Details
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010101
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    Tubulin nucleation and assembly in mitotic cells: Evidence for nucleic acids in kinetochores and centrosomes (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 1-15 
    Details
    ISSN: 0886-1544
    Keywords: centrosomes ; kinetochores ; microtubule initiation ; nuclease enzymes ; electron microscopy ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A lysed cell system was used to study the organelle structure and nucleation of exogenous tubulin at kinetochores and centrosomes in mitotic PtK2 cells. We have used this lysed cell system in conjunction with nuclease digestion experiments to determine which specific nucleic acids (DNA or RNA) are involved in either the structure and/or microtubule-initiating capacity of kinetochores and centrosomes. The results indicate that DNase I specifically decondenses the kinetochore plate structure, with the eventual loss in the ability of the chromosomes to nucleate microtubule assembly. DNase I had no effect on either the structure or nucleating capacity of centrosomes. Both RNase T1 and RNase A specifically attacked the amorphous pericentriolar material of the centrosomes, with a concomitant loss in the ability of this material to nucleate microtubule formation. Neither RNase appeared to affect the structure or nucleating capacity of the kinetochore. Therefore, the two types of nucleases appear to exert preferential effects on the different types of microtubule initiation sites in mitotic mammalian cells. The results suggest that DNA is a major component of the kinetochore, while RNA is a major component of the amorphous pericentriolar material. These findings support the concept that microtubule initiation sites in mitotic cells contain nucleic acids which are essential for the structural and functional integrity of the sites.
    Additional Material: 45 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010102
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    Redistribution of actin and fascin in sea urchin eggs after fertilization (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 31-40 
    Details
    ISSN: 0886-1544
    Keywords: actin ; fascin ; actin cross-linking proteins ; fertilization ; microvilli ; sea urchin eggs ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Following fertilization, the sea urchin egg cortex undergoes a structural change involving the assembly and organization of actin filaments into microvilli. Antifascin localizes this actin cross-linking protein in the microvilli of the fertilized egg cortex but no organized staining is present in the unfertilized cortex. Determination of the actin content of eggs using the DNAase I inhibition assay indicates that actin is about 1.4% of the total protein. Approximately 90% of this actin is soluble in low calcium isotonic extracts of unfertilized eggs while only 60-65% can be recovered in identical extracts of fertilized eggs. Similar measurements for fascin using a radioimmunoassay indicate this molecule represents about 0.3% of the total egg protein, essentially all of which is recovered in low calcium isotonic extracts of unfertilized eggs. After fertilization only 65-70% of this actin cross-linking protein is in the soluble phase. These results demonstrate a markedly different solubility for actin and fascin after fertilization, when the indirect immunofluorescence staining localizes fascin in the microvilli, and are consistent with the idea that fascin organizes newly polymerized actin filaments into the microvillar cores. A consideration of the amounts of actin and fascin incorporated into the cortex after fertilization and the number of microvilli on the egg surface indicates that the measured values are sufficient to account for the observed microvillar elongation.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010104
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    Control by calcium of the contractility of Labyrinthula slimeways and of the translocation of Labyrinthula cells (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 17-29 
    Details
    ISSN: 0886-1544
    Keywords: Ca-ion ; Labyrinthula ; contraction ; glycerination ; Ca-reservoir ; cell movement ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Colonies of Labyrinthula, a colonial marine protist, expand by protrusive movements of the specialized slimeways. The movements recorded in time-lapse films are of two types - filopodial and lamellipodial - and occur at rates equivalent to those of cell translocation.Evidence is presented that Ca2+ regulates the contraction of the actomyosin system of filaments present in the slimeways of Labyrinthula. In glycerinated models or in colonies exposed to ionophore A23187 contraction is evidenced by the occurrence of periodic contractions of the slimeways, giving them the appearance of strings of beads. Glycerinated slimeways contract on the addition of Ca2+ and ATP while slimeways provided with ionophore A23187 contract on addition of Ca2+ alone. The concentration required is 1.1 × 10-7 M Ca2+ while concentrations of 6.2 × 10-8 or lower were ineffective. Rates of contraction were measured in time-lapse films which provide evidence that contractions and beading occur everywhere in the slimeway system. When beading occurs, the 6-nm filaments transform from an array of parallel single filaments into an interwoven meshwork.We have identified by pyroantimonate-OsO4 fixation, as possible Ca2+ reservoirs, deposits of Ca2+ in bothrosomes - structures through which cell secretions pass into the slimeways. The electron-dense deposits are located at the base of the bothrosome and disappear after incubation with EGTA. We propose that the translocation of cells as well as the movements of slimeways may be regulated by the cells through the local measured liberation of Ca2+ from the bothrosome where it is sequestered.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010103
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    An analysis of spindle ultrastructure during anaphase of micronuclear division in Tetrahymena (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 41-61 
    Details
    ISSN: 0886-1544
    Keywords: mitosis ; mitotic spindle ; kinetochore ; microtubule ; micronucleus ; Tetrahymena ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Mitotic micronuclei were isolated from Tetrahymena thermophila and data on spindle ultrastructure were obtained from serial, transverse sections. Comparison of data from nuclei at meta- and early anaphase with data from nuclei at late anaphase showed that during anaphase, sister kinetochores move from the equator to the spindle poles, but kinetochore translocation occurs without any apparent change in either the number or length of kinetochore microtubules. This unprecedented result is ascribed significance with regard to the mechanism of kinetochore transport since there are only a limited number of ways that result could be achieved. The organization of the peripheral sheath changes during anaphase as evidenced by gaps in the sheath at late anaphase. Numerous kinetochore and non-kinetochore microtubules are located in polar regions of the spindle at late anaphase, whereas those regions contained only peripherally arranged microtubules at earlier stages. Tracking of individual kinetochore microtubules in late anaphase nuclei showed that some of them appeared to become incorporated into the peripheral sheath near the pole. At early and late anaphase, crossbridges connect adjacent microtubules throughout the spindle poleward to the kinetochores, as well as in the interzone.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010105
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    Physarum myosin light chain binds calcium (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 63-71 
    Details
    ISSN: 0886-1544
    Keywords: Physarum polycephalum ; myosin light chains ; polyacrylamide gel electrophoresis ; calcium ; cytoplasmic streaming ; actomyosin ATPase regulation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Myosin from the slime mold Physarum polycephalum contains three sizes of polypeptides: a heavy chain and two light chains, LC-1 and LC-2. Using a simple qualitative test for calcium binding by comparing electrophoretic migration of the polypeptides in sodium dodecy1 sulfate (SDS) acrylamide gels in the presence and absence of calcium, we have found that Physarum myosin light chain LC-2 migrates with an apparent molecular weight of 16,900 daltons in the presence of the metal ion chelator ethylene glycol bis (B-aminoethyl ether) N,N′-tetraacetic acid (EGTA). However, if calcium chloride is added to the sample prior to electrophoresis, the apparent molecular weight decreases to 16,100. Lanthanide and cadmium ions, but not magnesium, can substitute for calcium. Because the ionic radii of Ca2+, La3+, and Cd2+ are almost identical, we conclude that Physarum myosin LC-2 possesses a very size-specific binding site for calcium. Physarum myosin LC-1 and the heavy chain give no evidence for binding calcium by this test. Since cytoplasmic streaming in the plasmodium of Physarum requires calcium, our evidence indicates that the calcium-binding property of Physarum myosin LC-2 may be important in regulating the production of force by actomyosin in the ectoplasm. Unexpectedly, the myosin light chain in Physarum capable of binding calcium, LC-2, is the essential light chain, while LC-1 is a member of the regulatory class of myosin light chains [V. T. Nachmias, personal communication]. Until now, essential myosin light chains have not been shown to have high affinity divalent cation binding sites. This means a new version of the myosin-based model for actomyosin regulation by calcium may be required to explain cytoplasmic movement in Physarum, and perhaps in other motile systems involving cytoplasmic myosins as well.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010106
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    The role of the extracellular matrix in cell motility in fibroblast aggregates (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 99-112 
    Details
    ISSN: 0886-1544
    Keywords: cell motility ; extracellular matrix ; collagen ; glycosaminogly cans ; collagenase ; hyaluronidase ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effect of specific components of the extracellular matrix on the motility of tissue cells was studied using organ-cultured aggregates of embryonic fibroblasts. Spherical aggregates of chick embryo heart and skin fibroblasts were fused with [3H]-thymidine-labeled aggregates of the identical cell type. The movement of labeled cells into the unlabeled partner aggregate served as an estimate of cell motility in the cultured tissue-like aggregates. Collagenase treatment decreased the collagen content of heart fibroblast aggregates and increased cell motility; ascorbic acid treatment increased the collagen content of skin fibroblast aggregates and decreased cell motility. Reduction of the glycosaminoglycan content with testicular hyaluronidase had no measurable effect on cell motility in heart fibroblast aggregates.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/cm.970010108
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    Identification of genetic elements associated with muscle structure in the nematode caenorhabditis elegans (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 73-97 
    Details
    ISSN: 0886-1544
    Keywords: nematodes ; muscle structure ; mutants ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A search for new mutants with altered body-wall muscle cell structure has been undertaken in the nematode C elegans. One-hundred seventeen mutants were isolated after mutagenesis with ethyl methanesulfonate or ultraviolet light, enrichment by a motility-requiring test, and screening by polarized light microscopy; 102 of these mutants were in ten previously established genes, whereas 15 mutants permitted the identification of seven new complementation groups in C elegans. Two of the new genes map on linkage group I (unc-94 and unc-95) and four genes are sex linked (unc-96, unc-97, unc-98, and unc-99). One complementation group (unc-100) could not be mapped because of the special characteristics of its cohort mutants. Representative mutants of the mapped genes were examined by polarized light and electron microscopy. All of the mutants exhibit disruptions of the normal A and I band organization of thick and thin filaments. Several of the mutants produce collections of thin filament-like structures. In one of these cases, HE177 demonstrated collections of somewhat wider, intermediate-sized filaments as well, and the HE195 mutant produces paracrystalline aggregates of thin filaments amidst looser arrangements of similar structures. The mutants in newly identified genes, as well as the new mutants in previously established genetic loci, have promise as tools in the study of myofibrillar assembly and function. Among the 22 complementation groups associated with body-wall structure in C elegans, it is likely that some genes code for regulatory and morphogenetic functions in addition to the well-studied structural, contractile, and calcium-associated proteins in muscle.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010107
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    Tubulin content and synthesis in differentiating drosophila cells in culture (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 113-129 
    Details
    ISSN: 0886-1544
    Keywords: tubulin ; Drosophila ; β-ecdysterne ; differentiating ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Drosophila Kc cells exposed to physiological doses of the moulting hormone, β-ecdysone, elongate, become motile, and subsequently aggregate. This pattern of morphogenesis was found to require the assembly of a microtubular cytoskeleton. Tubulin content was significantly increased in hormone-treated cells when compared to controls, as measured by a 3H-colchicine-binding assay. However, determinations of rates of tubulin synthesis and breakdown revealed no difference between control and hormone-treated cells for either parameter. When tubulin content was assayed by methods that do not depend on colchicine-binding activity, no difference between hormone-treated and control cells was observed. These results are discussed in terms of a model in which β-ecdysone affects the distribution of tubulin in “assembly-active” and “assembly-inactive” pools.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010109
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    Meeting report (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 159-162 
    Details
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010112
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    The formation and elongation of filopodia during transformation of sea urchin coelomocytes (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 131-140 
    Details
    ISSN: 0886-1544
    Keywords: sea urchin coelomocytes ; motility ; filopodial formation and elongation ; ciné film analysis ; scanning electron microscopy ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Sea urchin coelomocytes were examined during their morphological transformation from petaloid to filopodial forms by scanning electron microscopy and ciné film analysis. Petaloid coelomocytes have a variable morphology but, in general, consist of numerous thin sheets of cytoplasm, the petals, arranged in three dimensions around a central nuclear region. The transition to the filopodial form can occur in either substrate-attached or suspended cells and begins with the formation of several microspikes at the edge of each petal. These become more apparent as the cytoplasm between each microspike/filopodium is retracted centripetally. Concomitantly, the diameter of the flattened cell is increased by as much as twofold as the filopodia actively lengthen at a uniform, average rate of 0.5 μm/minute. The transformation process requires ca 15 minutes and is complete when the cell diameter no longer increases. These filopodia are functionally distinct from the passively produced retraction fibers observed in cultured mammalian cells. The formation of filopodia is biphasic and includes both a cytoplasmic retraction phase and an active extension phase.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/cm.970010110
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    Invited review: Guidance cue patterns and cell migration in muiticeliuiar organisms (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 141-157 
    Details
    ISSN: 0886-1544
    Keywords: axon guidance ; chemotaxis ; haptotaxis substrate pathways ; development ; pattern biology ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In multicellular organisms, guidance cues are either diffusible molecules or cellular or extracellular surfaces that are found in reproducible locations and that orient migrating cells and cell processes. The pattern of the guidance cues usually determines the complex in vivo migration routes of motile cells and cell processes. Within organisms, guidance cues are found to be organized in two general patterns: (a) broad gradients - such as diffuse chemotactic gradients; (b) discrete routes (substrate pathways) - such as chemotactic gradients confined to long channels, and such as the axon surface which represents a long specific highway for migrating Schwann cells.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010111
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    Announcement (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 163-163 
    Details
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010113
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    Statement of purpose (1980)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 167-167 
    Details
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970010114
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    Pharmacokinetics of bretylium in man after intravenous administration (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059384
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    Accumulation in the peripheral compartment of a linear two-compartment open model (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059451
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    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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    The effect of short term incubation in vitro on the RNA content of regenerating mouse epidermis (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 349-353 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The effect of short term incubation in vitro on RNA content in regenerating and normal epidermis has been investigated. Regenerating mouse epidermis was incubated for three hours, either attached to its underlying dermis or by itself, in either buffered sucrose or Roswell Park Memorial Institute culture medium at 26°C or at 37°C. There is a significant loss of RNA when regenerating epidermis is incubated without being attached to its underlying dermis, at either 26°C or 37°C, although there was little loss of DNA, good incorporation of (3H) orotic acid into RNA, as well as good preservation of epidermal histological details. In contrast, when regenerating epidermis was incubated attached to its dermis, little loss of RNA occurred. Similarly, incubating normal epidermis attached to its dermis results in no loss of RNA. These conditions also result in no significant loss of DNA, good incorporation of (3H) orotic acid into RNA, and preservation of epidermal histological details.
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960311
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    American association of anatomists. Pages 1A-50A (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. A1 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Abstracts of papers presented at the 93rd meeting of the American Association of Anatomists a t Omaha under the sponsorship of the University of Nebraska School of Medicine, April 26, 27, 28, 29, 30, and May 1, 1980.The abstracts are listed in alphabetical sequence by senior author as follows: scientific papers from platform, poster presentation, or motion picture demonstration; special sessions on history and stereoprojection; and papers by title.Names of authors who are guests of the Association are marked with an asterisk. In addition, the letter “G” following the number of the paper and the term “sponsored by” is used to denote a graduate student presentation by an individual in hislher terminal year of graduate study, sponsored by hislher major professor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960313
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    American association of anatomists. Pages 151A-200A (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. A151 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960316
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    Heterogeneity of the MtTW15 mammosomatotropic tumor. II. Characterization of parenchymal cells by superimposition immunocytochemistry and electron microscopy (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 301-311 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Large MtTW15 tumors, which secrete growth hormone (GH) and prolactin (PRL), are composed of ovoid, elongated, and angular cells which demonstrated interdigitating processes and junctional complexes. The majority of the cells were essentially agranular, but two types of granulated cells were identifiable. One class of granulated cells contained moderate to sparse populations of round dense-cored granules measuring up to 250 nm in diameter. Rod-shaped to filamentous mitochondria with an electron-dense matrix were characteristic of a second class of granulated cells with pleomorphic granules of various sizes and electron densities. Images of exocytotic release of the round dense-cored granules were frequently seen, but were not observed with the pleomorphic granules, many of which were judged to be lysosomes. Superimposition immunocytochemistry revealed hormones only in the granulated cells with round to ovoid granules. Morphometry indicated that hormone specific subpopulations of tumor cells can be identified since PRL secretory granules were significantly smaller than GH secretory granules (149 ± 6 nm for PRL versus 221 ± 9 nm for GH, P 〈 0.001). The vast majority of immunopositive cells contained only GH or PRL, but a few were observed containing both hormones. Ovoid to irregular-shaped nuclei, large lipid inclusions, numerous free ribosomes and polyribosomes, moderate development of the rough endoplasmic reticulum, and prominent Golgi profiles were characteristics of all cell types. Irrespective of the presence or absence of cytoplasmic granular elements, particles resembling viruses were encountered in many tumor cells, and these frequently appeared to be budding into the cisternae of the endoplasmic reticulum.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091960306
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    Developing innervation of the chick heart: A histofluorescence and light microscopic study of sympathetic innervation (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 333-340 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The available descriptions of the development of sympathetic innervation of the chick heart conflict with the known sympathetic innervation of the adult chicken heart. The adult heart is innervated by bilateral sympathetic cardiac nerves originating from the first thoracic sympathetic ganglia. These nerves travel lateral and anterior to the lung and join the vagi just before entering the pericardium along the great vessels. Using catecholamine histofluorescence techniques and silver preparations, we have observed the development of the sympathetic cardiac nerves. The sympathetic cardiac nerves arise from the first thoracic sympathetic ganglia on the 7th day of incubation. They grow lateral and then ventral to the developing lungs to join the vagi, and are found in the bulbar region of the heart and atrium on the 10th day of incubation. Fluorescent cells without processes mark the course of the sympathetic cardiac nerves and are present in the bulbar region on the 10th day and thereafter. Sympathetic ganglion cells lose their fluorescence between day 8 and day 16 of incubation. This is presumably due to dilution of the transmitter in the rapidly increasing volume of cytoplasm in the sprouting neurons. Small intensely fluorescent (SIF) and adrenal medullary cells do not undergo a diminution of fluorescence during this period. SIF cells appear well differentiated at 16 days.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960309
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  • 78
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    Extracellular spaces of the rat pars intermedia as outlined by lanthanum tracer (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 355-360 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The extracellular spaces of the rat pars intermedia were examined after perfusion with fixative containing lanthanum. The tracer reveals complex and extensive interdigitations among secretory cells. Spaces appear continuous with extracellular “channels” between the epithelial cells lining the hypophyseal cleft. Some suggestion for close contiguity between endocrine cells was present as “narrowing” or discontinuous areas within lanthanum-filled spaces. Extracellular regions surrounding nerve fibers and terminals appear continuous with the spaces between secretory cells. Areas between cells are thought to provide access to vascular and local neurotransmitter input, as well as to provide an extensive area for extrusion of peptide hormones and endogeneous opiates.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960312
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  • 79
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    American association of anatomists. Pages 51A-100A (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. A51 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960314
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  • 80
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    American association of anatomists. Pages 101A-150A (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. A101 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960315
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  • 81
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    American association of anatomists. Pages 201A-257A (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. A201 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960317
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  • 82
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    Secretory mechanisms of human ceruminous glands: A transmission and scanning electron microscopic study (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 363-372 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Two secretory mechanisms (eccrine and apocrine) were observed by transmission and scanning electron microscopy in the same secretory cells of the human ceruminous glands.The eccrine secretion occurs as a typical exocytosis by fusion of the limiting membrane of the secretory granule with the apical plasmalemma. The apocrine secretion is more complex and takes place by sequential steps: bulging of the cellular apex into the lumen, constriction of the projection, and detachment of it from the cell. This mechanism generally causes the removal of the entire projection all at once by decapitation at its base; some variations of this process have been found, however, and are described in the present work.A double membrane, apparently separating the apical protrusion from the rest of the cell, is noticeable in our photographs. Nevertheless, even if this membrane is very similar to a demarcation layer, we consider it as an intercellular double membrane separating two obliquely sectioned cells.
    Additional Material: 18 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091960402
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  • 83
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    A histochemical analysis of polyanionic compounds found in the extracellular matrix encountered by migrating cephalic neural crest cells (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 401-412 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Neural crest cells destined to form craniofacial primordia initially are “seeded” into and subsequently migrate through the extracellular matrix (ECM) of a cell free space (CFS) between the surface ectoderm and the underlying mesoderm. Utilizing histochemical procedures for polyanionic compounds, we have demonstrated that both sulfated and nonsulfated glycosaminoglycans (GAG) are present in the CFS of the cephalic region of the chick embryo and that their distribution and structural organization vary with the passage of neural crest or mesodermally derived (MD) mesenchymal cells through it. In stages 7 and 8 embryos a predominance of fine filamentous strands composed primarily of nonsulfated, carboxyl-rich GAG is seen spanning intercellular spaces between adjacent tissues and MD mesenchymal cells. In older embryos (stages 9 and 10) much of the filamentous material is replaced by coarse fibrillar strands or amorphous material which coats the surfaces of MD mesenchymal and neural crest cells as they invade the CFS. Using enzymatic digestions (Streptomyces and testicular hyaluronidase) and the critical electrolyte concentration procedure, data suggest that the fine filamentous matrix onto which the neural crest cells migrate consists mainly of hyaluronate with lesser amounts of chondroitin and some sulfated GAG present. The coarse fibrillar matrix that appears after passage of either neural crest or MD mesenchymal cells through the original CFS contains strongly sulfated polyanionic material, predominantly chondroitin sulfates A, C. Since GAG is located ubiquitously within the ECM of embryos at various stages, the role of GAG, if any, in the transfer of developmental information may be of a general nature (ie, stimulus of motility) rather than of specific morphogenetic cues (for specific differentiation into craniofacial primordia).
    Additional Material: 11 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091960405
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  • 84
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    Serous cysts of the aging guinea pig ovary. III. Permeability of the cyst epithelium to lanthanum and horseradish peroxidase (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 213-219 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The permeability of the epithelium lining serous cysts of the guinea pig ovary was examined using lanthanum and horseradish peroxidase (HRP). Both lanthanum and HRP introduced at the luminal surface of the cyst penetrated to the basal region filling caveolae in both lateral and basal cell surfaces. Within three minutes of vascular infusion of HRP, the tracer was detected between epithelial cells and in caveolae on their lateral and basal surfaces but not associated with intracellular organelles. There was no change in the intracellular distribution of HRP after ten minutes. It was concluded that the epithelium was permeable to the tracers within this time period but that pinocytosis and transport of these tracers through the epithelial cell were not demonstrated.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091970210
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  • 85
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    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980) 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970201
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  • 86
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    Effects of estrogen and androgen on the ultrastructure of secretory granules and intercellular junctions in regressed canine prostate (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 111-132 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Epithelial cells in the prostate of the castrated or hypophysectomized dog were studied by thin-section and freeze-fracture electron microscopy to determine in vivo responses to estradiol-17β 17-cyclopentylpropionate (ECP) and testosterone cyclopentylpropionate (TCP). Particular attention was given to changes in specific organelles and intercellular junctions that might reflect hormone action. The few secretory granules that remain in the regressed epithelium (vestigial granules) serve as markers of prior androgen responsiveness. Pharmacologic doses of ECP caused regressed glandular cells to acquire a novel phenotype. Characteristic features of these estrogen-modified glandular (EMG) cells are newly formed secretory granules and tonofilament bundles that coexist with vestigial granules, thus demonstrating bipotentiality of response. Glandular cell-tight junctions appear unaltered by the endocrine manipulations. Although EMG cells have squamous cell features, tight junctions remain intact. Desmosomes in the canine prostate are dimorphic and are classified 70F and 100F according to the width of the filaments that converge on the dense plaques. In intact dogs, 100F desmosomes are associated with basal-reserve cells, whereas only the 70F variety is found between glandular cells. TCP treatment does not alter this distribution. Following ECP administration, both 70F and 100F desmosomes are present between EMG cells. The coexistence of newly formed secretory granules and tonofilaments of 100F desmosomes in the same EMG cell represents estrogen-induced bidirectional differentiation. Our findings indicate that androgens and estrogens are individually capable of controlling the expression of secretory granules and desmosomes. In intact animals, male and female sex hormones may act in concert to direct epithelial cell differentiation of the prostate.
    Additional Material: 19 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091970202
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  • 87
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    Immunocytochemical analysis of prolactin production by monolayer cultures of GH3 rat anterior pituitary tumor cells: I. Long-term effects of stimulation with thyrotropin-releasing hormone (TRH) (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 153-162 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Thyrotropin-releasing hormone (TRH) stimulates prolactin production in cultured GH3 rat anterior pituitary tumor cells. For correlation of cell-by-cell prolactin distribution and intracellular hormone concentration, GH3 cells were grown to plateau-phase density on glass coverslips in plastic dishes. Acetone-fixed, cell-bearing coverslips were stained for prolactin by an immunoglobulin-peroxidase bridge technique (Mason et al., '69); cells on the plastic dishes were assayed for prolactin (microcomplement fixation immunoassay, Tashjian, '73) and protein content. Intracellular prolactin, unaffected quantitatively by acetone fixation and choice of substratum, was localized immunocytochemically by a granular brown precipitate, abolished if anti-prolactin serum was preabsorbed with rat prolactin or omitted from the protocol. Intracellular prolactin was maximized with colchicine (5.0 × 10-6 M; final 3 hr of incubation) in control and TRH-treated (10 ng/ml; 48 hr) GH3 cell cultures. A total of 8,500 cells were classified by light microscopy as unstained, heavily (H) or moderately (M) stained for prolactin. In controls, 35% of cells were prolactin-positive: 6% H and 29% M. After TRH, 45% were positive: 7% H and 38% M. Although prolactin-positive cells were unevenly distributed, comprising 25% to 46% of cells in individual microscopic fields in controls, TRH increased the proportion of M cells in all areas. TRH treatment raised prolactin levels to 450% of control, but mathematical analysis attributed less than 30% of the increase to new prolactin-positive cells. We conclude that TRH acts on GH3 cultures principally by raising the mean hormone content of individual positive cells rather than by increasing the proportion of cells committed to prolactin production.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091970205
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  • 88
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    A random arrangement of albumin-containing hepatocytes seen with histo-immunologic methods. II. Conditions that produce the artifact (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 195-203 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The cellular immunolocalization of albumin in rat liver has been studied as a function of various physiological and physical conditions. Our observations show that the prime requisite for accurate immunolocalization of albumin and other hepatic-based proteins is the complete removal of blood and especially plasma from sinusoids and the perisinusoidal space of Disse prior to fixation.Fixation of blood-filled liver specimens results in the antifactual entrance of plasma constituents into hepatocytes. When the fixative used is formaldehyde, the artifactual uptake occurs primarily into hepatocytes that have a high glycogen content. Fixation of blood-filled liver with acetic acid-ethanol causes a massive influx of plasma into all hepatocytes. On the contrary, with blood-free liver, varying the type of fixative consistently demonstrates that all hepatocytes normally contain albumin, transferrin, and fibrinogen simultaneously.Increasing the time between cessation of blood flow and outright fixation by either withholding the fixative or by impeding its diffusion through the specimen causes a progressive loss of antigenicity of albumin. The same result ensues when specimens remain in contact with the fixative for an extended time.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970208
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  • 89
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    Placental permeability during early gestation in the hamster. Electron microscopic observations using horseradish peroxidase as a macromolecular tracer (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 221-238 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The permeabilities of the parietal yolk sac placenta and the preplacental region of the hamster conceptus during early postimplantation (day 8) were compared by means of electron microscopy and a macromolecular protein tracer, horseradish peroxidase (HRP). HRP was administered by injection into the maternal venous system; samples of the two placental tissues were obtained for examination at intervals between 4 minutes and 1 hour later. The three layers of the parietal yolk sac wall (from outer to inner: capsular trophoblast, Reichert's membrane, parietal endoderm) appeared to provide little impediment to the passage of HRP from perivitelline maternal blood spaces to the yolk sac cavity. HRP passed through the outer trophoblast layer, both by way of intracellular fenestrae (60-200 nm diameter) and narrower intercellular channels, and completely permeated the meshwork of Reichert's membrane within minutes after injection. The inner parietal endoderm cell layer was widely discontinuous and clearly presented no barrier to HRP movement. HRP reaching the yolk sac cavity was avidly endocytosed by the visceral yolk sac epithelium. In contrast to the parietal yolk sac, the preplacental region of the conceptus was impermeable to HRP. Zonular occluding junctions located between contiguous cells of the chorionic ectoderm layer of the preplacenta were the obvious barrier to the HRP molecules. These results suggest that in this rodent species, during the early postimplantation period of gestation, the parietal yolk sac placenta potentially plays a more important role in the maternal-embryonic transfer of macromolecular substances than does the preplacenta.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970211
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  • 90
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    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980) 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970301
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  • 91
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    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980) 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970401
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  • 92
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    The myelinated fibers of the deep branch of the ulnar nerve at the wrist in bonnet monkeys (Macaca radiata) and of some of its branches to the hand (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 387-396 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In order to estimate the peripheral nervous correlates concerning the motor performance of the hand, the myelinated fibers of the deep ulnar nerve and some of its branches to the intrinsic muscles of the monkey (Macaca radiata) hand have been enumerated and their caliber spectra plotted. The content of the myelinated sensory fibers in the deep ulnar nerve was found to be 70% of the total. This high figure is attributable to the fact that 25-50% of the myelinated fibers in the deep ulnar nerve are destined to innervate the joints of the hand. Approximately 50% of the myelinated fibers in nerves to the intrinsic muscles of the hand were sensory.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970403
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  • 93
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    Muscle sarcomere length following passive jaw opening in the rabbit (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 435-440 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Sarcomere lengths were measured microscopically in formalin-fixed jaw muscles of 14 rabbits divided into two groups; jaw open, and jaw closed. The measurements were compared by means of a nested analysis of variance. The sarcomeres of the jaw open group were longer in the masseter and temporalis muscles (jaw elevators) and shorter in the digastric muscle (jaw depressor) than were those of the jaw closed group. In the jaw closed position, sarcomeres in the deep portion of the masseter muscle become markedly shorter than those in the superficial part of the muscle. The values for sarcomere length in the masseter muscle of the jaw open group and the digastric of the jaw closed group are near the top of the ascending limb of isometric length-tension relation for the rabbit digastric muscle.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091970407
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  • 94
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    Proliferation of epithelial cells in the adult primate choroid plexus (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 495-502 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An adult rhesus monkey was injected intraperitoneally with [H3] thymidine (2.3 μCi/gram body weight) and perfused 90 minutes later with a mixture of aldehydes. One and a half micrometer plastic sections were then cut and dipped into liquid emulsion for radioautography. Labeled cells were observed in the choroid plexus of the anterior lateral ventricle; cell identification was evaluated using electron micrographs taken from serial thin sections of reembedded. radioautographic 1.5-μm sections. The ultrastructure and location of both mitotic figures and labeled cells confirmed the presence of undifferentiated basal choroid plexus epithelial cells in the adult primate central nervous system.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/ar.1091970411
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  • 95
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    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 198 (1980) 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091980101
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  • 96
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    Growth patterns and hormonal profile of male rats with protein-calorie malnutrition (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 339-354 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A condition of protein-calorie malnutrition was precipitated in young Sprague-Dawley male rats at 20 days of age using an 8% low protein diet (LPD). At five-day intervals for up to 50 days of age, the rats were studied to determine the effect of an LPD on the reproductive axis of the endocrine system. Daily monitoring of the body weight, as well as the consumption of food, kilocalories, and protein was conducted. The same parameters were followed over the identical time peroid in a group of animals designated as controls which were fed a standard laboratory diet (SLD) containing 27% protein. The controls showed a linear growth rate over the 30-day experimental period. In comparison, the malnourished rats grew more slowly so that by 50 days of age, their mean body weight was 68.9 ± 3.1 g as compared to 249.1 ± 6.1 g for the controls. The daily food, kilocalorie, and protein intake by the experimental animals were also appreciably less. The pituitary gland, ventral prostate gland, testes and liver were smaller in the animals fed the LPD. This was observed as early as five days after initiating the dietary regimes and remained a consistent observation until the end of the experiment. In general, the absolute weights of these organs in the 50 day-old malnourished rats were similar to those found in 25 to 26 day-old animals fed the SLD. The relative weights of the pituitary gland and liver remained similar between the two animal groups. The testes and ventral prostate gland, however, were relatively smaller in the malnourished animals at nearly every time interval studied. On light microscopic examination of the testes, it was found that normal maturation of the germ cells failed to occur in all but one of the experimental animals, whereas maturation proceeded normally in the rats fed the SLD. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), and testosterone were lower in the malnourished animals at all ages studied. These hormones did not exhibit the fluctuations that were seen in the controls and are typical in rats that are becoming sexually mature. The effect of protein deficiency on the concentration of the pituitary gonadotrophins was more varied. FSH concentrations were consistently lower, PRL was moderately affected, and LH remained essentially unchanged. Hypothalamic LH-releasing hormone was measured and found to be significantly less in the rats fed the LPD at most of the time intervals examined. These results indicate that the hypothalamo-hypophyseal-gonadal axis is impaired when the consumption of proteins and calories is decreased. The possible involvement of extrahypothalamic centers in the control of hormone secretion in the protein-deficient rat is discussed.
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    URL: http://dx.doi.org/10.1002/ar.1091970308
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    Quantitative cell changes and vascularisation in the early corpus luteum of the pregnant rat (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 369-374 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Early corpora lutea (CL) of the rat were histologically examined on Day 1, 2, 4, and 6 of gestation. Measurements were taken of total volume and of the number of luteal and endothelial cells in one CL of both ovaries of five rats at each stage examined. CL volume increased over the 6 days from --0.76 to 1.39μl and peripheral plasma progesterone levels from 8.1 to 33.2 ng/ml. The number of luteal cells per CL (range 303,000 to 37,000) did not significantly change, and there was no evidence of mitosis or death amongst these cells. Luteal cell volume increased from 1.74 to 3.49 pl and nuclear volume from 0.25 to 0.38 pl, the former being the major cause of CL growth. The CL appeared to be richly vascularized, even on Day 1, and the number of endothelial cells per CL (range 289,000 to 354,000) remained relatively constant over the period examined.It was concluded that the number of luteal cells per CL is determined prior to or around ovulation in the rat and that subsequent growth of the CL is due to hypertrophy and not hyperplasia.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970311
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  • 98
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    Electronic Resource
    Presynaptic bodies of auditory hair cells in old world monkeys (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 379-386 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Presynaptic bodies of auditory hair cells of Old World monkeys are separately differentiated in inner, as contrasted with outer, hair cells. The pre-synaptic bodies of outer cells are spherical and of variable electron density, and are thus similar to those of the labyrinth of vertebrates from fish to man. The difficulty in finding them, as compared with the relative ease of finding the presynaptic bodies of inner hair cells, suggests either that they are not present in all outer hair cells or that they undergo a regression-reconstitution cycle. The presynaptic bodies of simian inner hair cells are almost always ring-shaped. The few exceptions reinforce the impression of a later evolutionary development of the inner hair cell system. In any event, our findings serve to reemphasize the remarkable differentiation of outer and inner hair cell systems, and to deepen the mystery of their separate roles in audition.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970402
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  • 99
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    Electronic Resource
    Rat ovarian mast cells: Distribution and cyclic changes (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 197 (1980), S. 489-493 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Numerous tissue mast cells are present in the ovarian medulla and hilus and in the oviduct of rats. In the medulla, most of these mast cells are in the connective tissue of the stroma near blood and lymphatic vessels. During proestrus, many of the medullary mast cells totally degranulate and thus are not visible histochemically; they then regranulate during estrus. In contrast, the number of stainable mast cells in the ovarian hilus and oviduct does not change during the estrous cycle. Histofluorometric methods demonstrate that mast cells in the ovarian medulla and hilus, as well as the oviduct, contain histamine. In addition, the lining of small blood vessles in the ovarian medulla contains histamine. Thus, mast cell and blood vessel histamine secretion may play a role in ovarian function.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091970410
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  • 100
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    Electronic Resource
    Distribution of iron in the gastrointestinal tract of the common vampire bat: Evidence for macrophage-linked iron clearance (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 198 (1980), S. 183-192 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Iron in the tissues of the digestive tract of the common vampire bat (Desmodus rotundus) has been studied using histochemical, electron microscopic, and autoradiographic methods. This animal is an obligate sanguivore and has a daily intake of dietary iron 800 times that of man. The amount and distribution of tissue iron is not affected by either a single blood meal or starvation but does reflect the degree of siderosis of each animal's liver and spleen. By 7 days after the injection of a trace amount of 55Fe into the peritoneal cavity, labelled siderotic macrophages are present both on the serosa and within the walls of the stomach and intestine. In the lower intestine, such cells can be derived from the germinal centers of Peyer's patches. Siderotic macrophages are often situated in the lamina propria under areas of siderotic epithelium. Label is also present in the apical cytoplasm of mucosal epithelial cells, a region of abundant siderosomes. The ultrastructure of these organelles is extremely variable. Accumulations of membranous whorls and stacks, “stippled bodies,” ferritin molecules, and larger “ferruginous” complexes are bounded by one or a number of membranes. Iron is excreted when these epithelial cells are desquamated into the gut lumen. Similar Prussian blue-positive granules are present in the feces. Unlike other glandular cells, the parietal cells of the fundic caecum are siderotic. Their cytoplasm contains abundant siderosomes and ferritin with accumulations of amembranous ferritin bodies in the intracellular canalicular spaces. Prussian blue-positive granules are present in the lumens of fundic glands.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091980206
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