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  • 1980-1984  (1,058)
  • 1980  (1,058)
  • Life and Medical Sciences  (768)
  • Engineering General  (233)
  • pharmacokinetics
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Years
  • 1980-1984  (1,058)
Year
  • 1
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    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.
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  • 3
    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
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  • 4
    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.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    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
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    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
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    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
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    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
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    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
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    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
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    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.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    ISSN: 1432-1041
    Keywords: sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    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
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    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
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 37-43 
    ISSN: 1432-1041
    Keywords: caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
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  • 16
    ISSN: 1432-1041
    Keywords: bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    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.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
    ISSN: 1432-1041
    Keywords: patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A review of the published data on pharmacological closure of PDA in premature newborns shows that doses of 0.2 mg/kg indomethacin are less successful when given enterally (18 to 85% closure) than when given intravenously (88 to 90% closure). The elimination half-life is markedly prolonged in premature newborns compared to adults but there are wide differences between the patients and some discrepancies between mean values reported by various authors. The present study compares clinical and pharmacological results obtained in two groups of low birth weight infants with symptomatic PDA and treated with 0.2 mg/kg indomethacin: 7 patients treated enterally (group A) and 11 patients treated intravenously (group B). Permanent closure of the ductus was observed in 4 cases in group A and in 9 cases in group B. Transient closure was observed twice in each group. Of a total of 18 infants, 15 were saved (83%). One baby treated with indomethacin in spite of preexisting oliguria died from persistent anuria. Indomethacin plasma levels were measured by gas chromatography. The mean elimination half-life of the drug in group A (40.3±12.2 h) did not differ from that in group B (33.9±11.7 h). The apparent plasma half-life appears to be inversely correlated with gestational age (r=0.66,p〈0.05). No relationship between peak plasma levels and ductal closure was established, but a significant difference was found for area under the curve (0 to 24 h) between patients in whom a permanent closure was obtained and those in whom the closure was either transient or absent.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
    ISSN: 1432-1041
    Keywords: antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p〈0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    ISSN: 1432-1041
    Keywords: propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 279-283 
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
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  • 23
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    European journal of clinical pharmacology 18 (1980), S. 347-350 
    ISSN: 1432-1041
    Keywords: dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance 〈5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determined microbiologically by a plate diffusion method usingB. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
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  • 24
    Electronic Resource
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    European journal of clinical pharmacology 18 (1980), S. 383-390 
    ISSN: 1432-1041
    Keywords: prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was studied in six healthy volunteers given single oral doses of 2.5, 5 and 10 mg and placebo. It displayed a distinct positive inotropic action, manifested as a dose-related reduction of 16.5–27.2 msec in the pre-ejection period (PEPc; systolic time-intervals), and an increase of 4.2–5.9 Ω/sec2 in the Heather index (impedance cardiography). There was also a dose-related increase of 17.6–34.0 mmHg in systolic blood pressure, whereas diastolic pressure showed a slight, transient decrease, not related to the dose given. Heart rate rose by 5–12 beats/min. Stroke volume, as determined by impedance cardiography, increased by 24.2–28.5 ml at all three dose-levels. The effects of the drug developed rapidly, reaching their maximum within 30–60 min and lasting for about 4 h. The time-course of the effects corresponded to the plasma concentrations of the drug. The increases in systolic pressure and contractility were linearly correlated with the plasma concentrations (r=0.8−0.9,p〈0.001). The activity of prenalterol was also tested in the same volunteers after blockade of β-receptors with oxprenolol 80 mg. Under these conditions, oral doses of 25, 50 and 100 mg produced effects similar to or slightly less marked than those recorded after doses ten times lower in the absence of β-blockade. In a further 10 healthy volunteers, in whom tolerance to prenalterol was studied by repeated administration for 10 days of 5 mg four times daily, no change in blood chemistry, haematological parameters or urine values was found. The positive inotropic effect of a single oral dose of prenalterol 5 mg was also demonstrated by reference to the systolic time-intervals and the echocardiogram, in six patients with chronic heart failure, five of whom were digitalized. Prenalterol did not give rise to premature concentrations or other arrhythmias. The only untoward effect definitely attributable to the drug was palpitation, which was dose-related and as a rule was not unduly distressing; in one volunteer, however, the palpitations were unbearable. Prenalterol is a cardiostimulant agent with no direct effect on the peripheral circulation. On the basis of its pharmacological activity, it might well be of therapeutic benefit in all conditions in which an improvement in the pumping efficiency of the heart is required.
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  • 25
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
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  • 26
    ISSN: 1432-1041
    Keywords: beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
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  • 27
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    European journal of clinical pharmacology 17 (1980), S. 111-116 
    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.
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  • 28
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    European journal of clinical pharmacology 18 (1980), S. 263-268 
    ISSN: 1432-1041
    Keywords: naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7± 3.0 h (mean±SD) and it was not significantly prolonged in patients with renal failure (18.1±5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6± 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
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  • 29
    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.
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  • 30
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    European journal of clinical pharmacology 18 (1980), S. 423-428 
    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.
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  • 31
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    European journal of clinical pharmacology 18 (1980), S. 473-477 
    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.
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  • 32
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    European journal of clinical pharmacology 18 (1980), S. 505-509 
    ISSN: 1432-1041
    Keywords: cefadroxil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Cefadroxil have been studied in a crossover study involving 20 experiments in four healthy volunteers (19–24 years), after oral administration of five individual doses of 250, 500, 750, 1000 and 1500 mg of the antibiotic in capsules to each person. Plasma and urine concentrations of the antibiotic were determined microbiologically by a plate diffusion method. The antibiotic followed an open, single-compartment kinetic model. The plasma half-life was not significantly influenced by dose; the average was 1.438±0.220 h. The percentage of the antibiotic excreted in urine, too, was not significantly affected by the dose, being close to 80% of the quantity originally administered within 24 h. The values of Cmax and (AUC) increased linearly with the administered dose.
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  • 33
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    European journal of clinical pharmacology 18 (1980), S. 237-244 
    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.
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  • 34
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    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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  • 35
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    European journal of clinical pharmacology 17 (1980), S. 129-133 
    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.
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  • 36
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    European journal of clinical pharmacology 17 (1980), S. 275-284 
    ISSN: 1432-1041
    Keywords: chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
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  • 37
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    European journal of clinical pharmacology 18 (1980), S. 355-360 
    ISSN: 1432-1041
    Keywords: cis (Z)-flupentixol ; cis (Z)-flupentixol decanoate ; serum concentration ; biological half-life ; pharmacokinetics ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations of cis (Z)-flupentixol have been estimated in three male human volunteers who received cis (Z)-flupentixol by intravenous infusion, flupentixol (cis (Z)/trans (E) mixture, 1:1) orally as single and repeated doses, and i. m. cis (Z)-flupentixol decanoate in Viscoleo®. The intravenous data show that cis (Z)-flupentixol followed a multicompartment model, but it was not possible to fit the data to a two or three compartment model. The concentration curves after oral administration indicated relatively slow absorption with a peak concentration at 3–6 h, except for one case with peak at 1 h. The variation in the dosage interval after one daily oral administration was relatively limited (1.7–3.0 times), which indicates that 24 h is a reasonable dosage interval. Biological half-lives were estimated in different ways and showed some intra-individual variation; the half-life was of medium length (19–39 h). The serum concentrations after intramuscular injection of cis (Z)-flupentixol decanoate clearly demonstrated a depot effect, with a maximal concentration at 3–5 days after injection. The descending part of the serum curves allowed an approximate estimation of half-life of 3–8 days. This was not the elimination half-life, but in all probability the half-life of release of drug from the oil depot which was the rate-limiting step. From the areas under the serum concentration curves the fraction of orally administered cis (Z)-flupentixol available to the organism was calculated to be 55% (range 48–60%). The loss of drug might have been due to imcomplete absorption, but it is more likely that cis (Z)-flupentixol underwent first-pass metabolism in the gut wall and the liver. As the tablets contained about 50% cis (Z)-flupentixol, while the depot preparation contained 74% cis (Z)-flupentixol, the pharmacokinetically equivalent doses are: 10 mg tablet daily corresponds to 25 mg depot weekly. Calculation of systemic clearance gave values of 0.44–0.49 l/min, and an apparent volume of distribution was 12.5–17.2 l/kg.
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  • 38
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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  • 39
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    European journal of clinical pharmacology 18 (1980), S. 175-183 
    ISSN: 1432-1041
    Keywords: amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.
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  • 40
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    European journal of clinical pharmacology 18 (1980), S. 269-273 
    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.
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  • 41
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    European journal of clinical pharmacology 17 (1980), S. 339-348 
    ISSN: 1432-1041
    Keywords: acebutolol ; renal failure ; dialysis ; pharmacokinetics ; N-acetylmetabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acebutolol was studied in 10 healthy subjects with normal renal function (RN), in 13 patients with various degrees of renal failure (RI) and in 8 patients undergoing repeated haemodialysis (RD). A highly specific method was used to measure acebutolol (A) and N-acetylmetabolite (NAM). In RN the decrease in plasma levels was biexponential with an apparent plasma half lives in the slow phase of A: 8.8±2.3 h and NAM: 11.4±2.2 h. The percentage of the dose excreted unchanged was 13.9% and as NAM 25.8%. Renal clearances were A: 167±20 ml/min and NAM: 150±18 ml/min. The apparent plasma half life of acebutolol does not change according to the degree of renal insufficiency (RI: 7.0±2.7 h, RD: 7.5±2.7 h), while that of NAM is increased (RI: 21.5±10.1 h, RD: 32.3±16.8 h). There is a linear relationship between the apparent elimination rate constant of NAM and creatinine clearance (r=0.832,p〈0.001). In RI 21.7% of the dose is excreted in urine (A 5.0%, NAM 16.7%). When renal function is impaired, the renal clearance of A and NAM decrease in parallel with the creatinine clearance (A: r=0.874,p〈0.001; NAM: r=0.954,p〈0.001). During dialysis the plasma half life fell (A=3.4±0.9 h, NAM=7.4±2.6 h). The dialytic clearance was A: 42.6±12.7 ml/min and NAM: 40.4±16.3 ml/min, for a blood flow of 238±35 ml/min through a dialyser with a cuprophane membrane (Ultraflo II Travenol). Acebutolol is taken up by erythrocytes (λbc=0.50±0.04). The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal insufficiency.
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  • 42
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    European journal of clinical pharmacology 17 (1980), S. 379-384 
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
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  • 43
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    European journal of clinical pharmacology 17 (1980), S. 459-463 
    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.
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  • 44
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    European journal of clinical pharmacology 18 (1980), S. 51-53 
    ISSN: 1432-1041
    Keywords: pethidine ; phenobarbital ; aminoglycoside antibiotics ; pharmacokinetics ; clinical response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 45
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    European journal of clinical pharmacology 18 (1980), S. 55-63 
    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.
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  • 46
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    European journal of clinical pharmacology 18 (1980), S. 195-198 
    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.
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  • 47
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    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.
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  • 48
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
    ISSN: 1573-8744
    Keywords: compartmental analysis ; dynamic response ; identification ; linear systems ; modeling ; parameter estimation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Single input, single output experiments can result in nonunique solutions for the rate constants of a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is an infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtain a unique solution for the others. This paper considers such experiments and determines whether either the addition of an extra input (simultaneously with the first input) or the taking of an extra measurement would result in a unique solution. It is found that perturbing a second input can be useful, but only if the perturbation is of different shape from the first input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, though, the second measurement (for example, by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.
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  • 49
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacological effects ; two-compartment model ; tissue accumulation ; aminoglycoside antibiotics ; gentamicin ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Accumulation factors for the peripheral compartment in a two-compartment open model are derived. These expressions are contrasted with some previously published statements concerning drug accumulation. The utility of the new indices of accumulation is illustrated by reference to studies of gentamicin tissue uptake and its proposed relation to nephrotoxicity.
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  • 50
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
    ISSN: 1573-8744
    Keywords: bumetanide ; diuretics ; pharmacokinetics ; three-compartment model ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disposition of [ 14C] bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.
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  • 51
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
    ISSN: 1573-8744
    Keywords: bretylium ; pharmacokinetics ; healthy subjects ; antiarrhythmic ; twocompartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2β)of 7.8 hr and apparent volume of distribution (Vd,β)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.
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  • 52
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
    ISSN: 1573-8744
    Keywords: bufuralol ; renal failure ; pharmacokinetics ; metabolites ; renal clearance ; hepatic clearance ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1′-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Bufuralol was given orally to all subjects (20 mg); some of the healthy volunteers also received the drug intravenously (5 mg). Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its halflife of elimination was not markedly influenced. The behavior of 1′-hydroxy-bufuralol was consistent with a decreased renal clearance. The behavior of bufuralol in patients with renal failure was analyzed using the clearance approach. From this analysis it appears that the presystemic biotransformation of bufuralol is decreased in renal failure and that changes in systemic clearance are compensated in our patients by modifications of the volume of distribution, resulting in little net change in the halflife of elimination.
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  • 53
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 439-461 
    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.
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  • 54
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    Bulletin of experimental biology and medicine 89 (1980), S. 784-785 
    ISSN: 1573-8221
    Keywords: lithium ; psychotropic drugs ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 55
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    Journal of neural transmission 49 (1980), S. 281-285 
    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.
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  • 56
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    Cell Motility and the Cytoskeleton 1 (1980) 
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 57
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    Cell Motility and the Cytoskeleton 1 (1980), S. 17-29 
    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.
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  • 58
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    Cell Motility and the Cytoskeleton 1 (1980), S. 1-15 
    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.
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  • 59
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    Cell Motility and the Cytoskeleton 1 (1980), S. 31-40 
    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.
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  • 60
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    Cell Motility and the Cytoskeleton 1 (1980), S. 63-71 
    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.
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    Cell Motility and the Cytoskeleton 1 (1980), S. 99-112 
    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.
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  • 62
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    Cell Motility and the Cytoskeleton 1 (1980), S. 113-129 
    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.
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  • 63
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    Cell Motility and the Cytoskeleton 1 (1980), S. 73-97 
    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.
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  • 64
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    Cell Motility and the Cytoskeleton 1 (1980), S. 41-61 
    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.
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  • 65
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    Cell Motility and the Cytoskeleton 1 (1980), S. 159-162 
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 66
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    Cell Motility and the Cytoskeleton 1 (1980), S. 141-157 
    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.
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  • 67
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    Cell Motility and the Cytoskeleton 1 (1980), S. 163-163 
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 68
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    Cell Motility and the Cytoskeleton 1 (1980), S. 131-140 
    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.
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  • 69
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    Cell Motility and the Cytoskeleton 1 (1980), S. 167-167 
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 70
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    Journal of Morphology 163 (1980), S. 191-201 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Colonic organogenesis in rats was studied using light microscopic techniques for the demonstration of mucosubstances, glycogen, and connective tissue fibers.Crypts began as intraepithelial spaces which were in continuity with the colonic lumen. The cells forming the floors of these spaces invaded the nonsulfated acid glycosaminoglycan-rich mesenchyme as the basement membrane became discontinuous. As the diameter of the colon increased, the crypts lengthened and the lamina propria thickened until a layer of collagen and sulfated acid glycosaminoglycans formed at the bases of the crypts and the basement membrane was reestablished. The circular layer of the muscularis externa developed first, then the longitudinal layer, and finally the muscularis mucosae.Three types of mucous cells arose in these newly formed crypts. The initial epithelial cell type contained glycogen and gave rise to cells with apical coats of nonsulfated acid glycoproteins. This cell type was followed by the appearance of cells at the bases of the crypts containing nonsulfated acid glycoproteins. As the crypts lengthened, the goblet cells near the base contained nonsulfated and/or sulfated acid glycoproteins. Closer to and on the surface, the cells contained sulfated acid glycoproteins, a mixture of sulfated acid and neutral glycoproteins, or just neutral glycoproteins. Striated-border cells appeared intermingled with the mucous cells close to the bases of the crypts and continued onto the surface.A comparison was made between regeneration following placement of a surgical lesion in adult rats and events in organogenesis of the colon.
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  • 71
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    Journal of Morphology 163 (1980), S. 253-281 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Mastication has been studied by cinematography with synchronized electromyography (computer quantified and analyzed), while unanesthetized, freely feeding cats (Felis catus) were reducing equivalent-sized chunks of raw and cooked beef and cooked chicken. Cats reduce food on one side at a time, and their chewing cycles show both horizontal and anteroposterior deflections. Food objects are shifted from side to side by lateral jerks of the head and movements of the tongue.During the opening phase, the lower jaw is rotated relatively straight downward, and the digastric muscles are active in bilateral symmetry. Near the end of opening, the head jerks upward, both zygomaticomandibulares start to fire, and opening acceleration of the mandible decreases. Closing starts with horizontal displacement of the mandibular canines toward the working side, accompanied by asymmetrical activities from the working side deep temporalis and the balancing side medial pterygoid, as well as a downward jerk of the head. As closing proceeds, the mandibular canines remain near the working side and the working side zygomaticomandibularis and deep masseter are very active. Near the end of closing, the mandibular canine on the working side moves toward the midline, and adductors, digastrics, and lateral pterygoids of both sides are active. The adductors of the working side are generally more active than those of the balancing side.During a reduction sequence, the number and shape of the masticatory cycles, as well as movements of the head, during a reduction sequence are affected significantly by food type. As reduction proceeds, the duration of bite and the muscular activity (as characterized by number and amplitude of spikes) change significantly among muscles of the working and balancing sides. The adductors of the working side are generally most active when cats chew raw beef, less for cooked beef, and least for cooked chicken. In general, the adductor activity reflects food consistency, whereas that of the digastrics and lateral pterygoids reflects more the vertical and lateral displacements of the mandible. Statistical analysis documents that the methods of electrode insertion and test give repeatable results for particular sites in different animals. Thus, it should be possible to compare these results with those produced while other mammalas are masticating.
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  • 72
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    Journal of Morphology 164 (1980) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 73
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    Journal of Morphology 164 (1980), S. 25-38 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The clitellar epithelium of the freshwater oligochaete, Tubifex hattai, is composed of four types of gland cells (Type I, II, III, and IV), in addition to the cells generally found in the epidermis of this worm. The possible function of these gland cells in cocoon formation was studied with the electron microscope.Type I cells discharge their secretory granules by means of compound exocytosis and provide the materials for the future cocoon membrane. Immediately after completion of the discharge from Type I cells, Type II and III cells simultaneously discharge their secretory granules by means of compound exocytosis. The secretions from Type II cells constitute a colloid in the cocoon lumen and probably cause structural modifications in the future cocoon membrane. The secretory products from Type III cells form the cocoon plug. Although the process of discharge of secretory granules from Type IV cells was not observed, the contribution of these cells to the cocoon formation, producing hoops on the outer surface of the future cocoon membrane and fixing its anterior ends on the clitellum, is inferred from a morphological comparison of the hoop and the structure of the secretory granules.
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  • 74
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    Journal of Morphology 164 (1980), S. 69-81 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The distribution and activity patterns of monoamine oxidase and monoaminergic (formaldehyde-induced) fluorescence in the central nervous system of web-building and hunting spiders have been studied using histochemical methods. Enzyme activity occurred in the neuronal perikarya and in varying intensity in the structures of the neuropile mass, but only when dopamine, adrenaline, and noradrenaline were used as substrates. The optic centres of the spider brain normally exhibited relatively strong enzyme reactions when compared with the staining intensity of the rest of the nervous system.The neuronal cell bodies contained numerous granules of yellow-green fluorescence. Monoaminergic fluorescence of the neuropile was generally a weak green. The optic mases of the hunting spiders, the anterior bridge, several commissures of the ventral cord, and the neural lamellae showed a slightly higher fluorescence intensity and single fluorescing granules.The results obtained indicate the presence of catecholamines in the spider nervous system.
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  • 75
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    Journal of Morphology 164 (1980), S. 107-119 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The tongue of the striped dolphin, Stenella coeruleoalba, shows a V-shaped row of pits on its posterior dorsum. Their development is described on the basis of macroscopic and light microscopic observations on fetal, young, and adult stages. Four to eight pits occur, most often five in the adult. Anlagen of the pits first protrude as round epithelial thickenings which later increase in diameter and become thin. The circular primordia then sink, and grooves oriented both circularly and radially develop in the walls of the shallow pits thus formed. Pits and grooves deepen with development so that older pits become lined with conical projections. As pits grow further, they become elongated anterolaterally, retaining slit-like openings. Each pit in the adult is 2-8 mm long and about 1 mm wide. The pits are not derived from lingual gland ducts but develop independently. Taste buds resembling those of other mammalian tongues can be found in young dolphins but are few in number and limited to the thin epithelium of the pit projections and to that of the side wall of the pits. They first appear in the late prenatal period but degenerate in the adult. A rich nerve supply is observable in the lamina propria below taste buds in the calf. The pits and their projections in the dolphin correspond to the vallate papillae of other mammals, but whether each projection or a whole pit corresponds to a single vallate papilla is undecided.
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  • 76
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    Journal of Morphology 164 (1980), S. 139-159 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Two morphologically distinct structures occur on the surfaces of the oral papillae in several loricariid catfish species; namely, (1) typical vertebrate taste buds composed of receptor and sustentacular cells and (2) brushlike projections, termed epidermal brushes, that represent specialized epidermal cells containing keratin. Both of these structures were studied with the combined use of light microscopy and scanning and transmission electron microscopy. The general body surface, fins, and rostral cutaneous processes of some loricariid catfishes are covered with taste or terminal buds but lack the epidermal brushes. It is suggested that the epidermal brushes found on the oral papillae serve as protective devices for the taste buds and as abrasive surfaces for substrate scraping during feeding. The taste buds on the oral papillae may detect any gustatory stimuli from the resulting substrate disturbance. Comparative studies reveal many differences in the number and spatial arrangement of these two structures on the oral papillae among the several species of the Loricariidae examined. These differences may represent functional adaptations to the various modes of life in the Loricariidae.
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  • 77
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    Journal of Morphology 164 (1980), S. 215-233 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Electron microscope studies on Necturus maculosus oocytes ranging in size from 1.1-1.5 mm in diameter indicate the primary proteinaceous yolk to arise within structures referred to in other amphibian oocytes as yolk precursor sacs or bodies. The origin of these yolk precursor sacs appears to result from the activity of the Golgi complexes which form multivesicular and granular-vesicular bodies, the limiting membrane of which is at times incomplete. During differentiation, the yolk precursor sacs contain small vesicles similar in size to Golgi vesicles, larger vesicles similar to vesicular elements of the agranular endoplasmic reticulum and, on occasion, a portion of a mitochondrion. The interior of these sacs becomes granular, perhaps by a dissolution of the components just described, and soon becomes organized into a crystalline configuration.In oocytes 2.0-2.5 mm in diameter, an extensive micropinocytotic activity begins, continues throughout vitellogenesis, and constitutes the primary mechanism for the formation of secondary yolk protein. Numerous coated and smooth-surfaced vesicles, as well as electron-dense and electronlucent ones, fuse in the cortical ooplasm to form progressively larger yolk platelets.
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  • 78
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    Journal of Morphology 164 (1980), S. 235-263 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The asymmetric “punch and suck” mouthparts of larval Haplothrips verbasci develop from paired appendages in the late, post-anatrepsis embryo similar to those of other insects. Later, the labrum flexes ventrally over the stomodaeum, the right mandibular appendage degenerates, the maxillary appendages divide into inner (lacinial) and outer (stipital) lobes, and the hypopharynx arises from the venters of the mandibular and maxillary segments. All cephalic segments consolidate anteriorly prior to katatrepsis, their appendages flex ventrally, and the labial appendages fuse medially to form the labium and the primordia of the salivary glands and valve.The left mandible and the lacinial lobes of the maxillae invaginate into the head during and after katatrepsis to form the mandibular and maxillary stylet-secreting organs and these later deposit the cuticle of their respective stylets. Cuticle of the mandibular lever is deposited by labral cells at the apex of the mandibular sheath during and after hatching. That of each maxillary lever is secreted simultaneously into the lumen of a ventrally-directed diverticulum developing from stipital cells at the apex of each maxillary sheath.Shortly after katatrepsis, the maxillary and labial palpi originate respectively from cells in the outer wall of each stipital lobe and at the apex of the labium.Muscles of the mouthparts arise after katatrepsis from cephalic mesoderm and are fully-differentiated before cuticle of the mandibular and maxillary levers has been deposited.Gnathal morphogenesis in embryos of H. verbasci resembles that occurring in bug embryos and provides additional evidence that Thysanoptera and Hemiptera evolved from a common psocopteroid stem species having small, paired, biting and chewing mandibles and well developed lacinial stylets.
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  • 79
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The ventral surface of the most proximal tarsomere of each mesothoracic leg of the female black fly, Simulium venustum Say, bears approximately 60 bifurcate sensilla. Externally, a sensillum appears as a hair set into an asymmetric socket and with the distal tip flattened into two flared lobes. A single pore opens into a short groove at the base of the lobes. The hair shaft is divided into two lumina, one of which contains the dendrites. Each sensillum is innervated by four neurons, the dendrites of which extend unbranched to the pore. Sensillum liquor bathes the dendritic tips and extends through the pore into the adjacent groove and across part of the lobes. A sieve-like structure exists in the pore region of many if not all sensilla. At least two sheath cells are associated with each sensillum.It is suggested that, although the bifurcate sensilla have the internal structure associated with known contact chemosensilla, they have secondarily acquired an olfactory function which is facilitated by the flattened lobes which increase the adsorptive surface area.Along each side of the bifurcate sensilla is a row of sturdy spines, each innervated by a neuron with a tubular body, a characteristic of cuticular mechanoreceptors. These spines are likely tactile sensilla.
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  • 80
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    Journal of Morphology 165 (1980), S. 41-54 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Histology and cytology of dermal scales of the gymnophionans Ichthyophis kohtaoensis and Hypogeophis rostratus reveal their structure and the nature of their mineralization.Dermal scales are small flat disks set in pockets in the transverse ridges of the skin. Each pocket contains several scales of various sizes. A ring of “hypomineralization” of varying diameter may occur on scales of a particular dermal pocket but bears no relation to the diameter of these scales.Three different layers form the scales and are seen on sections perpendicular to the surface. The cells of the basal layer lie deepest. Each of the two or three more superficial fibrous layers is composed of bundles of fibres that are oriented in parallel. The orientation varies among layers. The striation of the fiber scales has a periodicity comparable to that of the surrounding dermal fibers. Squamulae form a discontinuous layer on the scale surface and are the only mineralized part of the scale. The minerals are deposited both on the collagen fibers passing from the fibrous layers into the squamulae, and in the interfibrillar spaces. Spherical concretions, either isolated or coalescent, reaching up to 1 μm, are found on the surface of the squamulae.The dermal scales of Gymnophiona present some analogies with those of evolved bony fishes. Their characteristics could make them an original model for the study of mineralization.
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  • 81
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    Journal of Morphology 165 (1980), S. 67-83 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Using light and electron microscopy, three hemocyte types are described in the hemolymph of the crayfish. The coagulocyte comprises 65% of the total hemocyte number and contains medium-sized cytoplasmic granules, abundant dilated rough endoplasmic reticulum, and a highly developed Golgi complex. It rapidly undergoes cytolysis in vitro and participates in coagulation by releasing the contents of its granules to the hemolymph. The granulocyte comprises 31% of the total hemocyte number and is capable of phagocytosis. It contains large, irregularly shaped cytoplasmic granules, a moderately developed Golgi complex, and moderate amounts of non-dilated rough endoplasmic reticulum. During coagulation in vitro, the cell attaches and spreads onto the substratum; this is followed by a slow intracellular granule breakdown and cytolysis. The amebocyte comprises 4% of the total hemocyte number and it is also capable of phagocytosis. It possesses small cytoplasmic granules, many vacuoles, a moderately developed Golgi complex, and large amounts of smooth endoplasmic reticulum. It is distinguished from the other two cell types by being stable and motile in vitro.
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  • 82
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    Journal of Morphology 165 (1980), S. 175-186 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This paper deals with the structure of gill epithelia in the sole, Solea solea, as revealed by transmission and scanning electron microscopy. In this marine teleost the chloride cell and its accessory cell form a cellular complex. Apically the plasma membranes of these cells are loosely juxtaposed, thus forming a leaky epithelium covering a large part of the gill.
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  • 83
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    Journal of Morphology 165 (1980), S. 187-204 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Common snapping turtles (Chelydra serpentina) lay nearly spherical, flexible-shelled eggs having an outer mineral layer composed of calcium carbonate in the aragonite form. The mineral layer is arranged into loosely organized groups of nodular shell units, with numerous spaces (or pores) between adjacent shell units. Shell units are structurally complex, consisting of an inner tip that is morphologically distinct from the main body of the shell unit. Contained within an intact shell unit at the interface of the tip and the main part of the shell unit is the central plaque, an apparent modification of the shell membrane that may serve to nucleate calcification of shell units during shell formation. The tips of shell units are firmly attached to a single, multilayered shell membrane throughout much of incubation. The calcareous layer begins to detach from the shell membrane about half-way through incubation, and changes in shell morphology attending this detachment indicate that snapping turtles may use the shell as a source of calcium during embryogenesis. The arrangement of the mineral layer into groups of shell units, the large number of spaces between shell units, and little or no interlocking of crystallites of adjacent shell units apparently are factors contributing to the ability of these eggs to swell as they absorb water.
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  • 84
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    Journal of Morphology 165 (1980), S. 255-260 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Three unusual highly ordered configurations of yolk protein in yolk precursor bodies are described. These differ from the crystalline structure of the main body of mature yolk platelets. One of these is an aggregation of paired membranes with a spacing of about 100 Å between the members of a pair. The paired membranes of such an aggregation may be straight, parallel, and very close together; they may appear as a tight whorl; or they may display an intermediate random arrangement with varying distances between pairs. Another configuration is a tubule with a diameter of about 450 Å, whose wall appears in cross section to consist of particles measuring 50 × 100 Å. A third configuration is a crystalline array of rows of angular-shaped particles with a spacing of about 160 Å. It is suggested that these may represent intermediates in the transition of vitellogenin to lipovitellin and phosvitin.
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  • 85
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    Journal of Morphology 165 (1980), S. 237-254 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The oral apparatus of neonatal and juvenile golden hamsters was investigated by clearing and staining of whole crania, videotaping of behavior, and electromyography of several jaw muscles. Chewing developed during the first postnatal week and matured in the second; however, suckling was still the primary mode of feeding. Micromovements of the jaws occurred early when the osseous skeleton and joints developed. Macromovements correlated well with EMG records and were limited to jaw opening at birth. Muscles of the oral floor generated large bursts of activity during jaw opening and tongue protrusion from 0 days postnatal (dpn), when simple and stereotyped gaping was induced, until 14 dpn, when movements were spontaneous and not stereotyped nor inducible. However, adductor muscle activity was brief, low in amplitude, and primarily involved with jaw stabilization until 4 dpn, when these muscles became active during closing the jaws; closing activity increased in frequency and amplitude until the end of the second week. Development of frequent, coordinated macromovements of chewing was associated with the refinement of joint structure and dental occlusion and with the growth of the craniofacial skeleton. Jaw movements and associated EMG's correlated better with available data on development of neural circuitry than with that for musculoskeletal development.
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  • 86
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    Journal of Morphology 165 (1980), S. 55-66 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: To examine the functional roles played by the lumbar spine during overground stepping, seven adult cats were run in electromyographic (EMG) experiments. Recordings were made bilaterally from mm. iliocostalis, longissimus dorsi and multifidus at a single vertebral level (L3) and from m. rectus abdominis. Stepping movements were monitored synchronously either by videotape or by high speed cinematography. During alternate use of the hindlimbs (walking and trotting), both epaxial and abdominal muscles were active bilaterally and biphasically. During in-phase use of the hindlimbs (galloping and half-bounding), single bursts of activity were observed. Phasic bursts of activity in rectus abdominus were reciprocal to those of epaxial muscles. Second bursts of activity in either group were noted infrequently. Recordings from the same back muscle at several vertebral levels indicated little difference from these patterns. Movements of the lumbar spine during galloping and half-bounding steps, both angular and linear, are easily correlated with muscle activity patterns. Movements of the lumbar spine during walking and trotting show no particular pattern. Only small angular and linear movements are found. It is concluded that the lumbar spine contributes substantially to step length and limb speed during galloping and half-bounding steps and the epaxial and abdominal musculature may also act as elastic bodies. During walking and trotting steps, the epaxial muscles are proposed to act to stabilize the pelvic girdle to provide a firm base for limb muscles which arise on the pelvis and are synchronously active.
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  • 87
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    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 85-116 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Lateral cortex is the most laterally placed of the four cortical areas in snakes. Earlier studies suggest that it is composed of several subdivisions but provide no information on their organization. This paper first investigates the structure of lateral cortex in boa constrictors (Constrictor constrictor), garter snakes (Thamnophis sirtalis), and banded water snakes (Natrix sipedon) using Nissl and Golgi preparations; and secondly examines the relation of main olfactory bulb projections to the subdivisions of lateral cortex using Fink-Heimer and electron microscopic preparations.Lateral cortex is divided on cytoarchitectonic grounds into two major parts called rostral and caudal lateral cortex. Each part is further divided into dorsal and ventral subdivisions so that lateral cortex has a total of four subdivisions: dorsal rostral lateral cortex (drL), ventral rostral lateral cortex (vrL), dorsal caudal lateral cortex (dcL) and ventral caudal lateral cortex (vcL). Systematic analyses of Golgi preparations indicate that the rostral and caudal parts each contain distinct populations of neurons. Rostral lateral cortex contains bowl cells whose dendrites arborize widely in the outer cortical layer (layer 1). The axons of some bowl cells can be traced medially into dorsal cortex, dorsomedial cortex and medial cortex. Caudal lateral cortex contains pyramidal cells whose somata occur in layers 2 and 3 and whose dendrites extend radially up to the pial surface. In addition, three populations of neurons occur in both rostral and caudal lateral cortex. Stellate cells occur in all three layers and have dendrites which arborize in all directions. Double pyramidal cells occur primarily in layer 2 and have dendrites which form two conical fields whose long axes are oriented radially. Horizontal cells occur in layer 3 and have dendrites oriented concentric with the ependyma. Fink-Heimer preparations of snakes which underwent lesions of the main olfactory bulb show that the primary olfactory projections to cortex are bilateral and restricted precisely to rostral lateral cortex. Electron microscopic degeneration experiments indicate that the olfactory bulb fibers end as terminals which have clear, spherical vesicles and asymmetric active zones. The majority are presynaptic to dendritic spines in outer layer 1.These studies establish that lateral cortex in snakes is heterogeneous and contains two major parts, each containing two subdivisions. The rostral and caudal parts have characteristic neuronal populations. Primary olfactory input is restricted to rostral lateral cortex and seems to terminate heavily on the distal dendrites of bowl cells. Axons of some of these cells leave lateral cortex, so that the rostral lateral cortex forms a direct route by which olfactory information reaches other cortical areas. The functional role of caudal lateral cortex is not clear.
    Additional Material: 18 Ill.
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  • 88
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 157-165 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The caudal neurosecretory system of the molly, Poecilia sphenops (Poeciliidae) was studied by light and electron microscopy. In this species the cell bodies form a focal nuclear group in the caudal spinal cord. The neurosecretory cells are in contact with glial elements, axon terminals, and the lumen of the central canal. The axons of the neurosecretory cells form a definitive tract, which leaves the spinal cord proper to penetrate a well defined neurohemal organ, the urophysis. The urophysis contains an abundance of neurosecretory granules within the neurosecretory axonal processes. This study is the first ultrastructural study of the caudal neurosecretory system in this family of fishes, which has been used as a neuroendocrine model. This species acclimates easily to the laboratory aquarium and may be most suitable for further studies on the effects of changes in external salinity on the caudal neurosecretory system.
    Additional Material: 11 Ill.
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  • 89
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 167-174 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The relationships between dimensions of book lung subunits were measured and analyzed as a function of body size in diverse spiders over a body mass range of 3.4 to 3,190 mg. Book lungs are the characteristic respiratory gas exchange organs in these arachnids. Actual gas exchange occurs across numerous air-filled cuticular plates, which invaginate hemolymph sinuses within the abdomens of these animals. Characteristic linear dimensions of these air-filled compartments reflecting diffusion paths scaled to the 0.2 power of body mass and showed only a fourfold increase over the size range in the sample. This deviation from isometric scaling in the direction obtained and its numerical similarity to scaling of alveolar dimensions to body size in vertebrates was interpreted as an adaptation to reduce diffusion distances between these compartments and vascular fluids. Conversely, lengths and widths of these plates scaled to the one-third power of body mass, isometric scaling, and increased between six-and eightfold over the size range. This result is consistent with the hypothesis that respiratory gas distribution within spider lungs is achieved by convective mixing as has been recently hypothesized.
    Additional Material: 4 Ill.
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  • 90
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 223-223 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 91
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 261-284 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This study carried out on the posterior caeca of Orchestia in intermolt by means of light and electron microscopy shows that the diverticula of the midgut consist of two segments which are different from an anatomical point of view. The distal segment is in close relationship to the dorsal blood vessel, whereas the proximal segment, twice as long as the distal one, only touches the haemocoel. The cells of the distal segment are characterized by a brush border, some apical extrusions, a great number of ribosomes, rough endoplasmic reticulum, often associated with the mitochondria, the matrix of which is clear, high activity of the Golgi complexes, and a great development of extracellular channels. All these features indicate an activity in synthesizing proteins and transport. In the proximal segment, the cells are characterized by a striated border, reduced intercellular space, and especially by a great development of the smooth endoplasmic reticulum sometimes associated with mitochondria having a dense matrix. These diverse features indicate absorption ion and water transport. From an ultrastructural point of view, the posterior caeca of Orchestia cannot be considered homologous to the Malpighian tubules. Whereas during molting the posterior caeca of Orchestia are sites of calcium storage, during intermolt they are probably involved in the processes of water and mineral regulation and excretion.
    Additional Material: 22 Ill.
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  • 92
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 1-25 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The paired spermathecae of Rhodnius are simple tubular out-pocketings of the common oviduct. Each consists of a short muscular proximal duct and the distal glandular region with a blind tapering end. The spermathecal wall has a cuticular intima, slender columnar epithelial cells and ensheathing longitudinal striated muscle, connective tissue, tracheoles, and nerves. Glandular epithelial cells possess an elaborate apical secretion-filled tubular inpocketing with an extensively folded plasma membrane. Laterally, cells interact by desmosomes, septate desmosomes, and extensive interdigitations. The cytoplasm is rich in longitudinally oriented microtubules associating with membrane densities along the invagination, lateral, and basal plasmalemmae. Apical concentration of mitochondria suggests their role in secretion or ion transport. The possible role of the spermathecae in maintaining the stored luminal sperm and its role in transmitting the mating stimulus is considered in light of the epithelial ultrastructure. The ultrastructure of the spermathecae of Rhodnius differs significantly from that of other insects.
    Additional Material: 35 Ill.
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  • 93
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 65-80 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Anatomical studies were conducted to characterize the source, type, and distribution of parathyroid gland innervation in European starlings. Denervation experiments demonstrated that the parathyroid glands and adjacent carotid bodies are innervated by nerve fibers originating in the nodose ganglion of the vagus nerve. In the parathyroid parenchyma, these fibers terminate adjacent to chief cells or near vascular smooth muscle. Vagal fibers also form synapses with catecholamine-containing glomus cells of the carotid body. Blood that first perfuses the carotid body subsequently perfuses the parathyroid parenchyma. These observations suggest that vagal innervation may influence parathyroid function in starlings either through direct chief cell innervation or through alteration of vascular perfusion. A neurohemal relationship also may exist between the carotid body and parathyroids.
    Additional Material: 13 Ill.
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  • 94
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 51-63 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The marine sponge Neofibularia irata contains four different categories of siliceous spicules. These spicules are evident in the tissues as distinct bundles that act to increase the structural rigidity of the sponge. All spicules have a normal structural morphology with silica deposition around a hexagonal axial canal containing a crystalline axial filament. The megasclere strongyles are secreted in typical megasclerocytes. The sigma and raphid microscleres are secreted in individual microsclerocytes that are grouped together in parallel to form loose bundles. However, the microxea microscleres are apparently secreted in distinct tight bundles (trichodragmas) within a single cell. These cells, containing between 13 and 39 spicules, are grouped to form large packets of bundles of spicules.
    Additional Material: 21 Ill.
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  • 95
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 27-36 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The nerve elements described by light microscopy for the hydrozoan planula have not previously been identified ultrastructurally. This electron microscopic study confirms the presence of two distinct nerve cell types in the planula of the hydroid Pennaria tiarella. Type I nerve cells occur at the base of the ectodermal epithelium just apical to the forming foot processes of the epitheliomuscle cells. The perikaryon contains mitochondria, microtubules, neurosecretory granules, and a prominent Golgi body. Neurites rich in microtubules project from these cells and form a nerve plexus of transversely and longitudinally oriented processes throughout the length of the planula. The Type II nerve cell extends from the free surface of the planula to the mesoglea and bears a single cilium surrounded by long microvilli. The Type I and II nerve cells closely resemble the sensory-motor-interneurons and neurosensory cells of Hydra.
    Additional Material: 7 Ill.
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  • 96
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 127-127 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 97
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    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 98
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 69-77 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The marine sipunculan worm, Sipunculus nudus Linné, possesses a voluminous coelomic cavity filled with a fluid containing different types of free cells. Most of them (more than 90%) are nucleated haemerythrocytes. They arise from free, small haemerythroblastic cells which are described in this report. Different kinds of leucocytes are also found in the coelomic fluid, particularly granulocytes which are phagocytic cells showing some similarities with vertebrate macrophages. These cells seem to arise from small hyalocytes, which are cells having morphological and physiological resemblances with vertebrate lymphocytes. It appears that the older granulocytes are progressively degranulated and give rise to large hyalocytes. Ciliary cells arising from small cells, very similar to small hyalocytes, have also been observed and it is supposed that they give rise to urn cells. Lastly, some of the biological functions of the free coelomic cells of the sipunculan worms are described.
    Additional Material: 15 Ill.
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  • 99
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 135-155 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Formation of a circular hole 8-10 mm in diameter in the calcified layers of the carapace from crabs in stage C4 of the molt cycle stimulates the tissue under and adjacent to the injury to deposit a unique calcified cuticular material below the intact membranous layer. Deposition was followed for 69 days using light microscopic histology, histochemistry, and scanning electron microscopy. Quantitative analyses of CaCO3 were conducted using atomic absorption spectrophotometry and Gran titration. Spatial distribution of CaCO3 was determined with X-radiography. A scab is formed by day two under the injury. At four days the epithelium changes from squamous to columnar and deposits a PAS-positive layer with an irregular lamellar fine structure, followed by highly organized lamellae structurally similar to normal exocuticle. Histochemically, however, these lamellae resemble normal endocuticle. CaCO3 is evident external to the outermost lamellae by day eleven as a fused mass of aragonite granules. The lamellar region calcifies proximally from the outer surface and is amorphous CaCO3. Repair cuticle is approximately 20%CaCO3 by weight.
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  • 100
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 99-133 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Study of the visceral anatomy of 41 specimens of amphisbaenians representing 13 genera shows that they share a very distinct structure which differs from that found in either snakes or typical lizards. The left lung is large while the right is rudimentary or absent (unique); the kidneys are freely suspended in the coelom by a mesentery (unique); the spleen is usually embedded in the anterior end of the pancreas (as in snakes); the gall bladder lies in a notch in the liver, and the kidneys lie opposite each other (as in lizards). The distinctness of this pattern supports the recognition of the Amphisbaenia as a separate suborder of the Squamata.
    Additional Material: 28 Ill.
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