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  • Electronic Resource  (218)
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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 509-515 
    ISSN: 1432-1041
    Keywords: cibenzoline ; pharmacokinetics ; bioavailability ; urinary excretion ; antiarrhythmic drug ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of cibenzoline (UP 339.01), a new antiarrhythmic drug, was studied after i.v. and oral administration to 5 healthy subjects. Cibenzoline levels in plasma and urine cibenzoline were measured by a GLC method. After i.v. administration, the total clearance was 826 ml · min−1. The fraction of cibenzoline excreted unchanged in the urine was 0.602 and it was correlated with the creatinine clearance. After i.v. and oral administration, the renal clearances were 499 ml · min−1 and 439 ml · min−1, and the half-lives were 4 h 01 min and 3 h 24 min, respectively. The differences were not significant. Availability by the oral route was 0.92, the maximum plasma concentration being observed at 1 h 36 min. The results were compared with those for other antiarrhythmic drugs.
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  • 102
    ISSN: 1432-1041
    Keywords: cimetidine ; intravenous infusion ; pharmacokinetics ; peptic ulcer ; duration of infusion ; acute dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of cimetidine administered by bolus intravenous injection to critically ill patients has been associated with serious cardiac arrhythmias, due presumably to high initial plasma concentrations. The aim of this study was to determine the range of infusion times of a single 200 mg dose of cimetidine which would avoid high initial drug concentrations while maintaining a duration of effective concentrations no less than that resulting from bolus injection. Computer simulations of both maximum plasma cimetidine concentrations and duration of effective plasma cimetidine concentrations versus duration of infusion were based on mean pharmacokinetic date from 6 peptic ulcer patients who had received cimetidine 200 mg i.v. over 5 min. The simulations indicated that to reduce maximum plasma cimetidine concentrations by at least 50%, while maintaining the duration of effective plasma concentrations, the infusion time should be at least 30 min and no longer than 4.5 h. The validity of the simulations was subsequently tested in 4 of the patients, who received cimetidine 200 mg i.v. over 30 min. The mean maximum plasma concentration for the 30 min infusion (4.57±0.53 µg/ml) was, as predicted, approximately half that corresponding to bolus administration in these patients (8.97±1.96 µg/ml). Moreover, the duration of effective concentrations for the infusion (1.43±0.28 h) was significantly greater than that for the 5 min infusion (1.21±0.31 h). We suggest that where an acute intravenous dose of cimetidine (200 mg) is indicated, it should be administered over at least 30 min rather than as a bolus.
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  • 103
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    Springer
    European journal of clinical pharmacology 25 (1983), S. 73-76 
    ISSN: 1432-1041
    Keywords: ketanserin ; pharmacokinetics ; protein binding ; excretion ; oral dosing ; i.v. injection ; first-pass effect ; antihypertensive drug ; serotonin antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Kinetic data for the new antihypertensive agent ketanserin were determined in six healthy subjects after single oral (40 mg) or intravenous (0.15 mg/kg) doses. Plasma protein binding was 94.0±1.8% (mean±SD). Cumulative urinary excretion of unchanged drug was less than 4% within 48 h following the single dose. The maximal plasma level (cmax) of 193±98.2 µg/l occured within 0.5 to 4.0 h after oral intake. The ketanserin plasma level declined biexponentially after oral administration, and triexponentially over the 36 h following intravenous injection. The terminal elimination half-life (term. t1/2) averaged 12.4±2.9 h and 12.8±4.8 h following oral and intravenous application, respectively. Total plasma clearance was 410±62.0 (i.v.) and 829±228 ml/min (p.o.) and the intravenous blood clearance averaged 602±91 ml/min, which indicates partly flowdependent hepatic elimination. A substantial first-pass effect led to a bioavailability of about 50% (range: 27–69%). Hepatic clearance of ketanserin followed the non-restrictive pattern. No change in blood pressure or heart rate was observed following ketanserin administration to normal volunteers.
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  • 104
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    Springer
    European journal of clinical pharmacology 25 (1983), S. 231-236 
    ISSN: 1432-1041
    Keywords: spirorenone ; pharmacokinetics ; aldosterone antagonist ; active metabolite ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of spirorenone in two groups of male volunteers have been determined after single and 14 daily doses of spirorenone 10 and 40 mg. Independent of the dose and pretreatment, spirorenone was absorbed with a half-life of 20–30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1–2 h. Disposition of the parent drug was biphasic with half-lives of 50–60 min (distribution) and 5–6 h (elimination). Neither significant accumulation nor enzyme induction were observed after prolonged treatment. In one test subject given spirorenone 40 mg, the concentration of an active metabolite, 1,2-dihydrospirorenone, was measured. This compound accumulated considerably after multiple dosing and the area under the plasma concentration-time curve increased from 16 to 52% relative to that of spirorenone itself.
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  • 105
    ISSN: 1432-1041
    Keywords: aspirin ; pharmacokinetics ; salicylate ; alcoholic liver disease ; young and elderly volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of the pharmacokinetic parameters derived from these profiles were not significantly different between young subjects, elderly subjects and subjects with alcoholic liver disease. Individual plasma albumin concentrations provided a better index of the unbound plasma salicylate clearances and salicylate plasma protein binding than the age of the subject or the presence of alcoholic liver disease. Highest unbound plasma salicylate concentrations were found in subjects with the lowest plasma albumin concentrations.
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  • 106
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    European journal of clinical pharmacology 25 (1983), S. 281-283 
    ISSN: 1432-1041
    Keywords: dyphylline ; pharmacokinetics ; bioavailability ; drug levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of 3 oral dyphylline preparations, solution (S), regular (R) and sustained release (SR), were studied in 8 healthy subjects (mean age 25 years). A single dose of each preparation, 20 mg·kg−1, was given at one week intervals and multiple serum samples obtained over 24 h. Drug levels were measured by high performance liquid chromatography. No adverse effects were found. The dyphylline half-life for the solution was 2.16±0.18 h and for the tablet 2.59±0.56 h. The mean clearance rate for S was 13.6±1.7 h−1 and volume of distribution 43.0±3.91. Peak concentration (Cmax, µg·ml−1), time of peak (Tmax, h), area under the curve (AUC, µg·ml−1·h) and relative bioavailability (RB, %), were determined for three preparations: The data confirm the short half-life of dyphylline, demonstrate a lack of toxicity for the 20 mg·kg−1 dose and establish bioequivalence for the products studied.
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  • 107
    ISSN: 1432-1041
    Keywords: phosphomycin ; pharmacokinetics ; impaired renal function ; “skin blister” ; interstitial fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The entry and persistence of phosphomycin in interstitial tissue fluid (ITF) were studied in 9 patients with normal renal function and 8 patients with varying degrees of renal impairment, all of whom received a single i.v. dose of 30 mg/kg. ITF was obtained from skin blisters produced by suction. The antibiotic followed a two-compartment open kinetic model. In patients with normal renal function, phosphomycin is incorporated rapidly into the ITF reaching a level of 60.4 µg/ml 60 min after administration. There was no statistically significant difference between the elimination rates from serum and ITF. The serum half-life of the slow disposition phase was 1.75 h in patients with normal renal function. There was a linear correlation between the elimination half-life of phosphomycin in serum and ITF in subjects with differing degrees of renal impairment.
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  • 108
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    Springer
    European journal of clinical pharmacology 25 (1983), S. 381-388 
    ISSN: 1432-1041
    Keywords: fenclofenac ; pharmacokinetics ; juvenile rheumatoid arthritis ; side effects ; synovial fluid drug level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty eight children (age range 3–17 years) with juvenile rheumatoid arthritis (JRA) received fenclofenac 10–25 mg/kg body weight daily on an open basis. Pharmacokinetic analysis was undertaken on plasma fenclofenac levels measured during the first 3 weeks of treatment. The peak concentration after the first dose was achieved in 2–8 h in non-fasting subjects and was linearly related to dose. The plasma level then decayed biexponentially, as in adults, the initial distribution phase extending to about 12 h after dosing. After treatment for 18 days, blood samples were taken during the 96 h following the last dose of the drug to define the steady state elimination profile. The elimination half-life was 25.4±7.9 h (n=17) and did not appear to be dependent on the daily dosage. A therapeutic drug concentration of ≥100 µg/ml emerged from subjective and objective estimates of the response to treatment and measurement of steady state fenclofenac concentration. Treatment response could be more accurately predicted with the aid of drug concentrations than from dosage alone, although the dose and the steady state drug concentration were positively and linearly correlated (r=0.61,p〈0.01). Of 16 children receiving doses in excess of 20 mg/kg/day, 3 experienced dose-related adverse effects, increased serum transaminase activity, vertigo and dyspnoea.
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  • 109
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    Springer
    European journal of clinical pharmacology 25 (1983), S. 395-398 
    ISSN: 1432-1041
    Keywords: haemofiltration ; cefoxitin ; pharmacokinetics ; renal failure ; beta-lactam-antibiotics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin was studied in patients with renal impairment during haemofiltration and in the intervening periods after administration of 30 and 15 mg/kg of the drug, respectively. Different pharmacokinetic patterns were established during haemofiltration and in the interim period, with average elimination half-lives of 11.85±4.3 and 3.41±0.6 h, respectively. The average fraction of the cefoxitin dose eliminated in haemofiltration was 0.62±0.11, more than that established in haemodialysis. In patients with terminal renal impairment undergoing haemofiltration every 48 h, a dose of 15 or 30 mg/kg is recommended at the start and at the end of each haemofiltration session.
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  • 110
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    European journal of clinical pharmacology 25 (1983), S. 407-412 
    ISSN: 1432-1041
    Keywords: ceftriaxone ; pharmacokinetics ; concentration-dependent binding ; volume of distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Guidelines presented previously for the analysis of plasma concentration versus time data for a drug exhibiting concentration-dependent plasma protein binding were successfully applied to the distributional parameters of a new cephalosporin, ceftriaxone. This approach provided several striking observations when the pharmacokinetics of ceftriaxone in a healthy and uremic population were re-examined. First, the parameter $$\bar f_P $$ converted the apparent dose-dependent distributional terms of ceftriaxone into a function of the concentration-dependent plasma protein binding. Second, a strong correlation between the term V SS U and the reciprocal of $$\bar f_P $$ was established within each of the two populations. While this $$\bar f_P $$ term accounted for the variability within the respective populations due to ceftriaxone-albumin binding differences, it did not account for all of the distributional differences between the two populations. The present analysis revealed that the altered physiologic state of uremia (larger plasma volumes and interstitial to intravascular albumin ratios), in addition to differences in plasma protein binding, dictated the distribution of ceftriaxone in healthy and uremic subjects. Furthermore, the binding-disposition model which accounts for the presence of plasma proteins outside the vascular space, was established to be appropriate in describing the distribution of ceftriaxone.
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  • 111
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    European journal of clinical pharmacology 25 (1983), S. 507-509 
    ISSN: 1432-1041
    Keywords: cefoxitin ; newborn infants ; bacterial infection ; pharmacokinetics ; cephalosporin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen patients less than 2 months old with bacterial infections caused by pathogens known or presumed to be sensitive to cefoxitin were studied. Cefoxitin was administered as an i.v. bolus injection over 15 min, every 8 h for 6 to 12 days, to a total daily dosage of 90 mg/kg. In 14 patients cefoxitin therapy resulted in eradication of the pathogen and in recovery from clinical signs of infection. Only one patient did not respond to cefoxitin therapy. No adverse clinical or haematological effects definitely caused by cefoxitin were observed. Plasma and urine samples collected after the first dose were assayed for cefoxitin by HPLC. Pharmacokinetic data indicated larger apparent volume of distribution (0.51/kg), a smaller plasma clearance (0.271/h/kg) and a longer half-life (1.43 h) than in adults. The plasma half-life was inversely correlated (p〈0.05) to the postnatal age of the patients. Cefoxitin may be safely used in infants with infections caused by susceptible pathogens.
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  • 112
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    European journal of clinical pharmacology 25 (1983), S. 651-655 
    ISSN: 1432-1041
    Keywords: loprazolam ; pharmacokinetics ; repeated dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml−1 (range 3.6 to 15.5 ng ml−1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean±SD half-life of 7.06±1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml−1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.
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  • 113
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    European journal of clinical pharmacology 25 (1983), S. 679-682 
    ISSN: 1432-1041
    Keywords: salicylic acid ; sex differences ; acetylsalicylic acid ; pharmacokinetics ; single and multiple doses ; elimination ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of disposition of total and free salicylic acid (SA) in blood plasma was evaluated after single and multiple oral administration of acetylsalicylic acid (ASA) to healthy female and male volunteers. In both single and multiple dose studies significant sex differences were found in the plasma levels of SA, which were due, at least in part, to individual, sex-determined differences in the rate of absorption and elimination of SA; a slower absorption rate in men reduced the magnitude of the peak plasma levels of SA. The corresponding area under concentration-time curves were always significantly lower. The elimination rate of SA in men was increased in comparison with women. The higher plasma clearance in men resulted from the kinetics of absorption and elimination. The sex differences appear to be clinical significance, since men achieved lower plasma levels of SA than women after the same weight-adjusted dose of ASA.
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  • 114
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    European journal of clinical pharmacology 25 (1983), S. 709-711 
    ISSN: 1432-1041
    Keywords: fluphenazine ; pharmacokinetics ; plasma concentrations ; intersubject differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of fluphenazine was investigated in six healthy volunteers following oral administration (5 mg). Using a sensitive and specific GC-MS procedure plasma fluphenazine concentrations were measured up until 32 h after drug administration. Peak plasma concentrations varied widely (range: 0.26–1.06 ng/ml) and were observed at 2.8±0.5 h following fluphenazine administration. The apparent terminal elimination half-life of fluphenazine was 33.1±8.1 h. The area under the plasma concentration-time curve differed widely between subjects (range: 7.1–28.6 ng/ml h) suggesting large interindividual differences in the extent of fluphenazine presystemic elimination.
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  • 115
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    European journal of clinical pharmacology 25 (1983), S. 791-795 
    ISSN: 1432-1041
    Keywords: procainamide ; acetylator phenotype ; antinuclear antibodies ; N-acetylprocainamide ; antiarrhythmic drugs ; cardiac arrhythmias ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and development of antinuclear antibodies (ANAs) during procainamide (PA) therapy were studied in 35 patients with ventricular arrhythmias. Sixteen of the subjects were rapid and 19 were slow acetylators. Twenty-six of them (13 rapid and 13 slow acetylators) received PA therapy (2.4 g sustained-release PA·HCl daily in three doses) for at least 16 weeks. On maintenance therapy, rapid acetylators had insignificantly lower serum PA concentrations and slightly higher N-acetylprocainamide (NAPA) concentrations than slow acetylators. The unchanged PA fraction (PA/PA + NAPA) in the rapid acetylators was somewhat lower than in the slow acetylators. Rapid acetylators excreted more NAPA in urine than did slow acetylators (p〈0.05), whereas the difference in PA excretion was not significant. More than 80% of the given drug was excreted as PA and NAPA. Spontaneous or exercise-induced arrhythmias were recorded in 6 rapid and 8 slow acetylators. ANAs (titre at least 20) appeared in 6 rapid and 8 slow acetylators. The mean time until ANA development in rapid acetylators was only marginally longer than in slow acetylators. The results suggest that acetylation phenotyping is not of great significance in predicting the development of ANAs during PA therapy.
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  • 116
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    European journal of clinical pharmacology 24 (1983), S. 21-30 
    ISSN: 1432-1041
    Keywords: clonidine ; bioavailability ; blood pressure ; elimination half-life ; pharmacokinetics ; plasma catecholamines ; rebound phenomenon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using considerably improved analytical methods, the kinetics and effects of clonidine were observed in healthy volunteers over periods of time more than 3 times longer than those previously reported. The high sensitivity and small work load of the newly developed method permitted the performance of low-dose and multipledose trials. 1. The complete bioavailability of clonidine and its elimination half-life (20 to 25.5 h) remained constant after single and multiple doses. 2. Approximately 62% of a given dose was excreted unchanged in the urine, independent of the quantity administered (0.075, 0.15, 0.2, 0.25 or 0.3 mg), the drug formulation (solution, tablet, Perlonget) or of the mode of administration (i.v., p.o.; single or multiple doses). 3. As the pharmacokinetics of the drug were affected by entero-hepatic circulation, it cannot be described by a conventional, open one or two compartment model. 4. The time courses of the plasma clonidine concentration and its drug effects ran asynchronously. 5. On cessation of chronic clonidine administration, blood pressure and plasma catecholamine levels increased to pretreatment levels without exhibiting any “overshoot” reaction.
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  • 117
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    European journal of clinical pharmacology 24 (1983), S. 139-140 
    ISSN: 1432-1041
    Keywords: benzodiazepine ; lormetazepam ; lormetazepam glucuronide ; transfer to milk ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 118
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    European journal of clinical pharmacology 24 (1983), S. 199-203 
    ISSN: 1432-1041
    Keywords: disopyramide ; arrhythmias ; controlled release tablet ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Steady state plasma levels and clinical effects of disopyramide have been compared following administration of standard capsules and controlled release (CR) tablets. Nineteen patients (29–70 years) with atrial or ventricular arrhythmias were treated for two weeks with disopyramide capsules 200 mg t.i.d. and then with CR tablets 300 mg b.i.d. for 14 weeks. After treatment either with capsules or CR tablets, plasma concentrations of disopyramide and its metabolite N-deisopropyldisopyramide were similar within 1 dosage interval. Maximum and minimum concentrations of the parent drug were 10.1±0.9 µmol/l (mean ± SEM) and 5.7±0.5 µmol/l with CR tablets, and 10.2±0.5 µmol/l and 5.6±0.5 µmol/l with standard capsules. The bioavailability of disopyramide was the same after capsules and CR tablets. Disopyramide, independent of the formulation, produced good antiarrhythmic effects. The side-effects reported on questioning were mainly of the anti-cholinergic type and there was no significant difference between the formulations with respect to their incidence, type or severity. Of 16 patients who stated a preference for one of the dosage forms, 11 prefered the CR tablets. The study confirms the good antiarrhythmic effect of disopyramide and shows that the CR preparation permits twice daily administration of disopyramide.
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  • 119
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    European journal of clinical pharmacology 24 (1983), S. 391-398 
    ISSN: 1432-1041
    Keywords: cefuroxime ; furosemide ; nephrotoxicity ; renal insufficiency ; pharmacokinetics ; clinical efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and clinical effects of cefuroxime were investigated in 5 patients with severe impairment of renal function (creatinine clearance ⪕ 23 ml/min), suffering from an urinary tract infection. Bolus i.v. injections of cefuroxime 750 mg b.i.d. or 750 mg once daily were given to the patients depending on the degree of renal impairment. The concentration of drug in serum and urine was measured during treatment, and pharmacokinetic parameters were evaluated on the second and last days; the parameters obtained on the 2 days did not differ significantly. Drug elimination half-life increased from 4.2 h (creatinine clearance 23.0 ml/min) to 22.3 h (creatinine clearance 5.0 ml/min) with decreasing renal function. The apparent volume of distribution ranged from 11.6 to 17.91, and showed a substantial increase to 29.61 in the patient with the poorest renal function. A linear correlation was found between the total and renal clearance of cefuroxime and the creatinine clearance; the extrarenal clearance was 8.24 ml/min. Concomitant treatment with furosemide did not impair renal function and no evidence of nephrotoxicity was found. The clinical efficacy of the drug was good. Symptoms of infection subsided after 3–4 days and the isolated pathogens were eradicated. No relapse or episodes of reinfection were observed in a following-up period of 3 months. The drug was well tolerated and no side effects or changes in haematological or biochemical values were seen.
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  • 120
    ISSN: 1432-1041
    Keywords: ranitidine ; duodenal ulceration ; pharmacokinetics ; non-responders ; therapeutic response ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of orally administered ranitidine were studied in 17 male patients with chronic duodenal ulceration. The patients were divided into 2 groups, 10 responders and 7 nonresponders, on the basis of their endoscopic response to ranitidine treatment. The 10 responders were studied both after a single 150 mg dose (SD) and after multiple dosing (MD) with ranitidine 150 mg twice daily for 4 weeks. The area under the curve (AUC) and maximum concentration (Cmax) were significantly higher (p〈0.01 andp〈0.05, respectively) after MD than after SD, but the half-life (t1/2) and minimum concentration (Cmin) 12 h postdosing did not differ. The non-responders were studied after MD only and their pharmacokinetic characteristics were compared with those of responders. No differences between the 2 groups were found. However, 2 non-responders had particularly low plasma ranitidine levels and high acid output. Such patients may need larger doses of ranitidine for adequate suppression of gastric acid. Five patients (4 responders and 1 non-responder) received ranitidine 20 mg i.v. The drug followed a two-compartment model, with mean values for t1/2β, volume of distribution steady-state and total plasma clearance of 80 min, 701 and 680 ml/min, respectively. The oral bioavailability of ranitidine in these 5 patients showed wide variation (27–76%; mean 51%).
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  • 121
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    European journal of clinical pharmacology 24 (1983), S. 689-694 
    ISSN: 1432-1041
    Keywords: isotretinoin ; major blood metabolites ; 13-cis-retinoic acid ; 4-oxo-isotretinoin ; 4-oxo-13-cis-retinoic acid ; pharmacokinetics ; dermatological disorder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A pharmacokinetic profile of isotretinoin and its major dermatologically active blood metabolite, 4-oxo-isotretinoin, was developed following a single 80 mg oral suspension dose of isotretinoin to 15 normal male subjects. Blood samples were assayed for isotretinoin and 4-oxo-isotretinoin using a newly developed reverse-phase HPLC method. Following rapid absorption from the suspension formulation, isotretinoin is distributed and eliminated with harmonic mean half-lives of 1.3 and 17.4 h, respectively. Maximum concentrations of isotretinoin in blood were observed at 1 to 4 h after dosing. Maximum concentrations of the major blood metabolite of isotretinoin, 4-oxo-isotretinoin, are approximately one-half those of isotretinoin and occur at 6 to 16 h after isotretinoin dosing. The ratio of areas under the curve for metabolite and parent drug following the single dose suggests that average steady-state ratios of metabolite to parent drug during a dosing interval will be approximately 2.5. Both isotretinoin and its metabolite can be adequately described using a single linear pharmacokinetic model.
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  • 122
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    European journal of clinical pharmacology 24 (1983), S. 695-702 
    ISSN: 1432-1041
    Keywords: isotretinoin ; 13-cis-retinoic acid ; 4-oxo-isotretinoin ; 4-oxo-13-cis-retinoic acid ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The multiple dose pharmacokinetics of isotretinoin and its major blood metabolite, 4-oxo-isotretinoin, were studied in 10 patients with cystic acne and 11 patients with various keratinization disorders. Blood samples were obtained at predetermined times following the first dose, interim doses and the final dose. Blood concentrations of isotretinoin and 4-oxo-isotretinoin were measured by a specific and sensitive HPLC method. A lag time was usually observed prior to the onset of absorption following oral administration of the drug in a soft elastic gelatin capsule. Absorption then proceeded rapidly and maximum blood concentrations usually occurred within 4 h of drug administration. The harmonic mean half-life for the elimination of isotretinoin by the cystic acne patients was approximately 10 h after the initial dose and did not change significantly following 25 days of 40 mg b.i.d. dosing. Steady-state blood concentrations remained relatively constant after the fifth day of dosing. The harmonic mean elimination half-life in the patients with various disorders of keratinization was about 16 h. The results of the 2 studies suggest that no significant changes in the pharmacokinetics of isotretinoin occur during multiple dosing and that the multiple dose pharmacokinetic profile is predictable and can be described using a linear pharmacokinetic model. This suggests that the steady-state concentrations of isotretinoin can be predicted from single dose data.
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  • 123
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    European journal of clinical pharmacology 24 (1983), S. 761-767 
    ISSN: 1432-1041
    Keywords: theophylline ; bioavailability ; sustained release tablet ; pharmacokinetics ; Theograd-250
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of theophylline after oral administration of a new sustained release tablet Theograd®-250 mg was studied in 7 healthy volunteers, under fasting and non-fasting conditions. Whilst fasting the bioavailability was moderate at 64±22% (mean±SD), whereas in the non-fasting state the relatively high bioavailability of 90±13% was found. The drug appeared to be significantly more slowly absorbed when a tablet was taken after a meal, than when it was ingested on an empty stomach. In the former case, the peak level was reached after 6.9±1.0 h, whereas in the fasting state the maximum serum concentration occurred 4.0±1.7 h after administration of the drug. Despite the slow absorption, the peak non-fasting level of 4.4±1.4 mg·l−1 was significantly higher than the 3.1±1.0 mg·l−1 observed in the fasting state. The profiles of the serum concentration-time curves showed that the concentration remained above 75% of Cmax for 8.7±1.3 h in the fasting and 9.0±1.1 h in the non-fasting state. It was concluded that to define the optimal dosage regime for sustained release oral dosage forms of theophylline, the influence of food on absorption from these preparations should be taken into account. Based on the present results, Theograd®-250 mg tablets have predictable absorption and a high (90%) bioavailability if taken after a meal.
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  • 124
    ISSN: 1432-1041
    Keywords: bufurlol ; pharmacokinetics ; oxidative polymorphism ; hydroxylation polymorphism ; betaadrenoceptor blocking agents ; phenotype ; interindividual variations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oxidative metabolism of bufuralol is under the same genetic control as that of debrisoquine and sparteine. 154 fasting volunteers received a 30 mg tablet of bufuralol and a blood sample was taken 3 h later. In poor metabolizers (8% of the sample) the plasma bufuralol concentrations were very high and the metabolite concentrations were low. The genetic oxidative status is a major source of interindividual variation in the plasma concentration of drugs that undergo oxidative metabolism.
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  • 125
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    European journal of clinical pharmacology 25 (1983), S. 91-94 
    ISSN: 1432-1041
    Keywords: triazolam ; geriatric patients ; hypnotics ; pharmacokinetics ; plasma concentration ; benzodiazepine ; alpha-hydroxytriazolam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum triazolam levels were determined in eight geriatric patients (average age 80 years) on Days 1 and 7 of administration of triazolam 0.25 mg once daily, 1 h after a standard breakfast. Triazolam was rapidly absorbed reaching average peak concentrations of 2.0 and 2.04 ng/ml, 1.5 and 1.38 h after administration on Days 1 and 7, respectively. The mean apparent elimination half-life was 1.41 h (range 0.73–4.13 h) on Day 1 and 1.37 h (range 0.69–3.36 h) on Day 7. There was no significant difference between mean serum triazolam concentrations or pharmacokinetic parameters on Days 1 and 7 of the treatment. Serum samples were also assayed for α-hydroxytriazolam, an active metabolite of triazolam, but none could be detected in any of the samples from Days 1 or 7, assay sensitivity 0.09 ng/2 ml serum. The range of half-lives of triazolam in the patients in the present study is in close agreement with that previously reported in elderly subjects. The study provides further evidence of the lack of change in pharmacokinetic parameters on multiple dosing and that drug accumulation did not occur.
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  • 126
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    European journal of clinical pharmacology 25 (1983), S. 347-351 
    ISSN: 1432-1041
    Keywords: ranitidine ; chronic renal failure ; pharmacokinetics ; duodenal ulceration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour of a single oral 150 mg ranitidine dose was studied in six patients with severe chronic renal failure (CRF) (creatinine clearance 2–18 ml/min) and compared to that in ten patients with duodenal ulceration but normal renal function (N) (creatinine clearance 69–125 ml/min). Although the maximum concentrations (Cmax) were significantly higher in CRF group when compared to N group (p〈0.025) there was no difference in the time taken to reach Cmax (t max). The area under the curve (AUC) was also significantly larger in the CRF group (p〈0.001) than in the N group. Within the CRF group there was a large variation in Cmax (CV = 38%) and AUC (46%) which may reflect variable bioavailability of ranitidine. The terminal elimination rate constant (β) was significantly smaller (p〈0.001) in CRF group when compared with N group resulting in a median t1/2 for the CRF group of 7.3 h, 2.4 times that of N group. The recovery of unchanged ranitidine in the urine was significantly less in CRF group (p〈0.001) despite a great interindividual variation in both groups. A significant linear relationship betweenβ and creatinine clearance was shown (r=0.81p〈0.001). The results indicate that ranitidine elimination is appreciably reduced in renal failure. It is tentatively suggested that the standard 150 mg dose should be halved while keeping the dose interval unchanged at twelve hours in patients with severe renal failure (creatinine clearance less than 30 ml/min).
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  • 127
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    European journal of clinical pharmacology 25 (1983), S. 673-677 
    ISSN: 1432-1041
    Keywords: metapramine ; pharmacokinetics ; doseconcentration relationship ; plasma levels ; i.v. administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of the plasma level metapramine following infusion at three different rates (1.18, 2.36 and 4.71 mg/h) has been studied in six healthy volunteers. The correlation coefficient of drug concentration and rate of infusion was 0.974 (α〈0.001, n=18). Plasma clearance, estimated from the steady-state level, varied from 68 to 107 l/h. 3 subjects also received 35 mg of drug by i.v. bolus injection and plasma concentrations were determined at set times for up to 24 h. The plasma level of metapramine decreased tri-exponentially, with a terminal half-life of about 7.4 h. The plasma clearance after i.v. injection was in good agreement with that observed during the infusion study. Apparent volumes of distribution ranged from 41.9 to 90.3 l.
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  • 128
    ISSN: 1432-1041
    Keywords: human insulin ; diabetes control ; blood glucose ; free insulin ; biosynthetic insulin ; semisynthetic insulin ; monocomponent insulin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen hospitalized insulin requiring diabetics treated with a single daily subcutaneous injection were randomly allocated either to a mixture of porcine Actrapid+Lente MC or a mixture of Regular+NPH—Biosynthetic human insulin (Study 1). In Study 2, 10 patients receiving two daily insulin injections were treated at random with either porcine Actrapid+Monotard, or Actrapid+Monotard—Semisynthetic human insulin or Regular+NPH—Biosynthetic human insulin. Once an optimal insulin regimen was obtained, circadian blood glucose and plasma free insulin profiles (7–9 time points) were determined with the two (Study 1) or three (Study 2) insulin preparations, keeping the doses of insulin constant. In Study 1 no significant difference in blood glucose (BG) or plasma free insulin (FIRI) profiles was observed. The mean daily blood glucose, the mean amplitude of glycaemic excursions (MAGE), the index of blood glucose control (M-value of Schlichtkrull), as well as the post-breakfast increases in blood glucose and mean free IRI, were similar with both types of insulin. In Study 2, BG and FIRI profiles were also similar, except for a significantly lower (p〈0.02) BG at 8.30 p.m. with both human insulins. No significant differences were found in free IRI at that time. Mean BG, M index, MAGE and mean FIRI were similar but the postbreakfast increase was significantly smaller with SHI. In conclusion, the pharmacokinetics of animal monocomponent, semisynthetic and biosynthetic human insulin appear similar, but evening BG control was better with both types of human insulins given twice daily.
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  • 129
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    European journal of clinical pharmacology 24 (1983), S. 7-14 
    ISSN: 1432-1041
    Keywords: oxprenolol ; coronary heart disease ; normals ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration profile of oxprenolol after intravenous bolus injection, during intravenous infusion and following sustained oral administration was studied in a total of 106 patients with coronary heart disease. Speed of onset of pharmacodynamic activity, as measured by suppression of isoprenaline tachycardia, was discernible within a few seconds of central injection and complete within 5 min in all patients; variability in response was small. Following both i.v. bolus and intravenous infusion, plasma oxprenolol concentrations showed considerable between patient variability The plasma concentration/time profile observed in 16 patients following single intravenous oxprenolol bolus therapy was substantially higher, particularly during the early distribution phase, than observed and predicted volunteer data. Higher plasma oxprenolol concentrations were also attained during the more extended time sampling of the infusion studies; these findings would be compatible with reduced oxprenolol clearance in patients with ischaemic heart disease. During chronic oral therapy there was a many-fold between-subject variability in plasma concentration achieved following a given ingested dose. Correlation of antagonism of exercise tachycardia inhibition with plasma oxprenolol concentration in 15 male volunteers demonstrated near complete blockade of exercise stimulation of chronotropic beta-adrenoceptors at an average plasma oxprenolol concentration of 150 ng/ml. In coronary heart disease, such plasma concentrations can most conveniently be achieved by a 4 mg oxprenolol intravenous bolus with simultaneous infusion of 0.05 mg/kg/h; however, these studies provide sufficient information to allow alternative regimens to be derived should lesser plasma concentrations be considered desirable.
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  • 130
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    European journal of clinical pharmacology 24 (1983), S. 209-215 
    ISSN: 1432-1041
    Keywords: sobrerol ; mucus liquefaction ; pharmacokinetics ; bronchial mucus level ; mass fragmentography ; metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic profile of Sobrerol, a mucolytic drug, has been studied in patients with acute exacerbations of chronic bronchitis and dense sputum. In addition to measurement of serum and urine levels, the concentration in bronchial mucus was also examined, and their correlation was calculated. Mass fragmentographic analysis was used to assay free sobrerol and its principal urinary metabolites hydrated carvone and glucuronidated sobrerol. After the doses and administration routes used, there appeared to be accumulation of sobrerol in bronchial mucus. This is a feature of great interest and value for a drug which has the specific action of liquefying mucus.
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  • 131
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    Archives of microbiology 134 (1983), S. 295-298 
    ISSN: 1432-072X
    Keywords: Actinomycetes ; Streptomyces thermoviolaceus ; Sporogenesis ; Spore ornamentation ; Cupular knobs ; Sheath ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The sporogenesis of aerial spores in Streptomyces thermoviolaceus corresponded to a common sporulation type in the genus. The sporulation septum was composed of an outer ring-shaped constriction wall and an inner interspace septum arising by the inwards growth of a double annulus. In mature spores the wall was composed of two layers, the outer one was part of the parent hyphal wall and septum material, the inner one was formed de novo. The spore chains were enclosed by the thin breakable sheath containing small rod-like elements. The ornamentation in the form of knobs, which were a characteristic feature of the species originated from the sheath. The knobs were hemispherical particles with an inner electron dense core and an outer electron transparent shell. The term “cupular knobs” was suggested for this type of tuberculate ornamentation. Frequently, the knobs became detached from the surface in which case the inner core separated easily from the shell.
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  • 132
    ISSN: 1432-072X
    Keywords: Cyanobacteria ; Ultrastructure ; Nitrogen fixation ; Water stress ; Taxonomy ; DNA ; Plasmids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Two strains of desiccation-tolerant coccoid cyanobacteria, Chroococcus S24, a marine form, and Chroococcus N41, a cryptoendolith isolated from a hot-desert rock, have been characterized. The mol % DNA base compositions of the strains are 47.1 and 48.9% respectively. Plasmid DNA was not detected in either strain. The pigment contents and nutritional characteristics of the strains are identical. Both lack phycoerythrinoid pigments and, in culture, behave as slow-growing halotolerant marine forms with elevated requirements for Na+, Cl−, Mg2+ and Ca2+. Sucrose was the only carbon source of those tested that supported photoheterotrophic growth. Each strain synthesizes nitrogenase under anaerobic conditions but not in air. Morphologically the two strains are indistinguishable. They are considered to be independent isolates of the same cyanobacterial species. Chroococcus N41 was studied in detail with the electron microscope. When brought to equilibrium at matric water potentials of-168 MPa and lower (to-673 MPa=c0.12a w) the protoplast shrinks, but the cells maintain the same size and diameter as those at-2,156 kPa (MN medium; control); the sheath expands and remains attached to the cell wall outer membrane by fibrils. The cell wall, cell membrane, thylakoid membranes, cyanophycin granules and carboxysomes appeared intact in desiccated cells.
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  • 133
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    Virchows Archiv 399 (1983), S. 177-189 
    ISSN: 1432-2307
    Keywords: Achilles tendon ; Tendon injuries ; Muscles ; Myofibrils ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unilateral tenotomy of the Achilles tendon was carried out in 60 rabbits. The limb was then either mobilized directly or immobilized for 10 to 35 days using a plaster usually after tendon suture. In certain cases the plaster was removed early (on the 7th or 16th day) and the animals were than allowed to use this leg. Separation between tendon ends was apparent from steel markers, placed close to each cut end of the tendon and examined by X-ray. The separation curve was biphasic and both the first and the inactive phase reflected the degree of tension over the tendon suture. However, during the second separation phase, which began between the 17th and 21st day, the separation gradually reached the same level in all groups. Enzyme histochemistry and electron microscopy revealed severe degenerative changes in immobilized and in shortened muscles. Furthermore, a gradual shift in fibre type characteristics from type 1 slow-twitch fibres towards type 2 fast-twitch fibres occurred. Rapid recovery followed removal of the plaster. The findings indicated that both degenerative and regenerative processes and adaptive processes had been initiated in all experimental muscles when the tendon continuity was broken. The adaptive processes progressed gradually during the five-week post-operative period and might have been responsible for the second phase of the tendon end separation. The fibre adaptation, i.e. the transformation, may be accounted for by changes in structure of the myofibrils and composition of the myosin molecules.
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    Virchows Archiv 399 (1983), S. 277-287 
    ISSN: 1432-2307
    Keywords: Pituitary ; Hyperplasias ; Immunocytochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Surgical specimens of 15 normal and 106 para-adenomous anterior pituitaries were studied immunocytochemically and in part electron microscopically for the presence of hyperplasia. GH cell hyperplasia was found in 13% of all normal pituitaries, in 6% of the cases with Prolactin secreting adenomas and in 9% of the cases with ACTH secreting adenomas. Prolactin cell hyperplasia occured in nearly equal percentages (17–23%) in normal pituitaries and in areas adjacent to GH-, Prolactin-or ACTH-secreting adenomas or adjacent to inactive adenomas. Previous findings of relatively more frequent Prolactin cell hyperplasia occuring together with Prolactin producing adenomas have to be revised. Prolactin cell hyperplasia as a primary source of hyperprolactinemia is very rare and almost always occurs in conjunction with oncocytic adenomas. ACTH cell hyperplasia was found in 13% of the normal pituitaries, in 14% of the cases with Prolactin secreting adenomas, in 58% of the cases with ACTH producing adenomas and in 40% of the pituitaries with GH secreting adenomas. We have no explanation for the latter result. ACTH cell hyperplasia may be the primary cause of Cushing's disease (18% of all Cushing cases). Hyperplasia of TSH cells in normal pituitaries was rare (7%) and with the exception of Prolactin producing adenomas (22%) was not found near adenomas. Clinical-pathological correlations are discussed.
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  • 135
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    Virchows Archiv 401 (1983), S. 89-97 
    ISSN: 1432-2307
    Keywords: Undifferentiated carcinoma ; Parotid gland ; Myoepithelial cell ; Epithelial cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two cases of undifferentiated carcinoma of the parotid gland were studied by light and electron microscopy. Light microscopy showed nests of ovoid cells with scanty cytoplasm and pyknotic nuclei in two cases. One case was the small-cell type, and another one was the large-cell type histopathologically. Electron microscopy showed two distinct cell types in each tumor: Case 1 (small-cell type). — An epithelial-like cell, and an irregular-shaped cell containing bundles of filaments suggesting myoepithelial differentiation. Case 2 (large-cell type). — An epithelial-like cell, and a large cell containing secretory-like granules. These findings support a salivary duct epithelial origin for these tumors.
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  • 136
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    Cell & tissue research 234 (1983), S. 411-425 
    ISSN: 1432-0878
    Keywords: Intestines (chicken) ; Innervation ; Catecholamines ; Adrenergic fibres ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Axons in the duodenum, ileum and rectum of the domestic fowl were identified as catecholamine-containing (CA) on the basis of positive reactivity following chromaffin fixation for electron microscopy. CA-axons in association with blood vessels in all regions of the intestine and in non-vascular sites in the small intestine had a ‘ typical’ adrenergic appearance, in that they contained many small granular vesicles (SGV) and variable numbers of large granular vesicles (LGV). In the rectum the non-vascular CA-axon profiles were atypical, in that there were many elongated LGV and few SGV, and the chromaffin reactivity was weak. The nerve profiles in the rectum were dramatically reduced following 6-hydroxydopamine and reserpine treatment and were absent in rectum cultured in the absence of extrinsic ganglia. It was concluded that the profiles, in spite of their low chromaffin reactivity, truely represent CA-axons. The possibility was raised that the atypical morphology and reduced chromaffin reactivity is due to the presence of adrenaline.
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    Cell & tissue research 234 (1983), S. 427-437 
    ISSN: 1432-0878
    Keywords: Corticotropes ; Rat fetus ; Ultrastructure ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Corticotropes of rat fetuses aged 16, 18 and 21 days were localized by the indirect antibody-enzyme method on semithin sections of the pituitary. The development of the ultrastructure of these cells was observed on consecutive ultrathin sections. In comparison with previous data our present results show that identification of a fetal cell type cannot be based entirely on morphological criteria. The structural peculiarities of corticotropes obtained from studies in vivo are compared with those observed in cells maintained in vitro.
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    Cell & tissue research 234 (1983), S. 679-689 
    ISSN: 1432-0878
    Keywords: Odontogenesis ; Rats ; Cyclophosphamide ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cyclophosphamide-induced changes in rodent odontogenesis were investigated by light and electron microscopy in four-day-old Sprague Dawley rats given one injection of 40 mg/kg of body weight of cyclophosphamide and killed at intervals of one hour, one day, one week and two weeks. Incisor and molar teeth were dissected from the animals, fixed in 2.0% glutaraldehyde in 0.1 M sodium cacodylate with 3.4% sucrose, and subsequently some were incubated for alkaline phosphatase reaction, and embedded in Spurr's medium for sectioning at light- and electron-microscopic levels. From three days a cell-sparse zone was created in the pulp in the growing end of the tooth and progressive cellular changes were observed which became more severe in the one-week and two-week specimens. Subodontoblast and adjacent pulpal cells were the most affected showing nuclear changes, damage to, or loss of, organelles, and inclusion bodies. Odontogenic epithelium was less affected and odontoblasts appeared to be unaffected by the drug. A new irregular matrix was laid down in the defect area and seemed to be the product of depolarized odontoblasts. This new matrix showed alkaline phosphatase activity, as did the cells embedded in it, and later it became mineralized. It is speculated that the polarity of odontoblasts might be maintained by an intact subodontoblastic layer; when this is lost the odontoblasts become depolarized and capable of secreting matrix from both ends.
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    Cell & tissue research 232 (1983), S. 579-591 
    ISSN: 1432-0878
    Keywords: Cavernous bodies ; Endothelial cells ; Respiratory activity ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Work on endothelial cells has been limited by the availability of procedures for obtaining such cells in quantities adequate for direct in vitro analysis. The present paper describes a method for the isolation of endothelial cells from bovine cavernous bodies. A number of cells ranging from 2.5 to 4 × 108 per animal has been obtained. The cells were identified as follows 1) presence of the “Weibel and Palade” bodies in the isolated cells, 2) “cobblestone” appearance of cell cultures, and 3) presence of factor VIII, as demonstrated by immunofluorescence assays. The cell viability at the end of the purification procedure was tested 1) by dye-exclusion tests and 2) by metabolic assays. Features of this preparation are 1) the very high yield of viable endothelial cells, 2) the absence of contamination by fibroblasts and smooth muscle cells and a very low contamination by erythrocytes and 3) the fine dispersion of the isolated cells. These properties allow functional and subcellular fractionation studies on freshly isolated endothelial cells of microvascular origin.
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    Cell & tissue research 233 (1983), S. 427-438 
    ISSN: 1432-0878
    Keywords: Myocardium ; Thunnus alalunga ; Ultrastructure ; Mitochondria ; Myofibrils
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The common ventricle in the heart of the Thunnus alalunga was studied. The ventricular myocardium consists of an outer compact layer and a thick inner spongy layer. The compact layer has slightly larger cells (4–6 μm diameter) than the spongy layer (2.5–5 μm diameter). Ultrastructurally the myocardium displays normal arrangements of myofibrils and mitochondria. The sarcoplasmic reticulum is poorly developed. The intercalated discs are simple with the fascia adherens being the most frequent junctional type observed; occasionally a desmosome was seen. Nexus type junctions are present but are unassociated with the intercalated discs. There are no t-tubules evident but the plasmalemma exhibits numerous caveolae which rarely form couplings with the sarcoplasmic reticulum. A morphometric analysis of the volume percent of mitochondria and myofibrils showed that the myocardial cells in the spongy layer of the heart have a significantly greater volume percentage of mitochondria than the compact layer. No significant differences were found between myocardial regions when the volume percentages of myofibrils were compared. The physiological studies revealed that the albacore tuna has heart rates (120 bpm) and ventricular blood pressures (100 mmHg) that are among the highest reported for fish.
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    Cell & tissue research 233 (1983), S. 523-537 
    ISSN: 1432-0878
    Keywords: Epididymis (rat) ; Myosin ; Actin ; Fibronectin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The anatomical distribution of smooth muscle actin, myosin, fibronectin and basement membrane has been investigated immunohistochemically, using the indirect immunofluorescence technique, in the rat epididymis. The findings were correlated with the ultrastructural organization of the organ. Actin was found to be distributed in the stereociliary region of the epithelial principal cells and in the terminal web region. Actin was also visible along the base of the epithelium. Myosin was detected in the terminal web and in the terminal bar regions of the epithelium. The contractile cells showed a strong stain for both proteins. Basement membrane immunoreactivity was distributed along the epithelial basement membrane and around the contractile cells of the wall. In the cauda, between the epithelium and the contractile cell layers, the lamina propria, containing blood vessels and a thin layer of cells, was negative for all antigens investigated. Fibronectin showed a granular distribution around the contractile cells, mainly in the cauda. The ultrastructural study showed only thin (5–6 nm in diameter) filaments in the stereocilia and terminal web region. Thin filaments were also visible in the cytoplasm of the basal cells, thus suggesting a contractile function of this cell type. The heterogeneous appearance of the contractile cells of the wall seemed to support the different contractile pattern of the epididymal regions: caput, corpus and cauda. The cells present in the lamina propria showed cytoplasmic vesicles with dark granules resembling the “A” cell granules of the endocrine pancreas and gut mucosa cells.
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    Cell & tissue research 233 (1983), S. 563-577 
    ISSN: 1432-0878
    Keywords: Nematocysts ; Structure ; Ultrastructure ; Function ; Cubozoa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Microbasic p-mastigophores, euryteles of two size groups, holotrichous isorhizas and atrichous isorhizas, comprise the cnidom of Chironex fleckeri, a cubozoan that has been responsible for several human fatalities. In its undischarged state each microbasic mastigophore of C. fleckeri consists of a capsule containing matrix and an inverted tube possessing a smooth-walled butt which is loosely coiled helically and which narrows to form a thread that is tightly coiled helically and markedly pleated. Both butt and thread carry three helices of spines and contain a granular matrix. During discharge, the proximal butt spines form initially a piercing stylet. Granular material from the butt and thread is released prior to the release of capsular material. Each eurytele possesses a tube with a butt composed of three bulbs, the middle bulb bearing long spines. Each holotrichous isorhiza possesses a coiled tube bearing small spines along its length. Each atrichous isorhiza exhibits a tube that is devoid of spines and loosely folded in the undischarged condition. The probable role of each type of nematocyst is inferred from its structure and features that enable the ready separation of the nematocysts of C. fleckeri from those of scyphozoan jellyfish are discussed.
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    Cell & tissue research 233 (1983), S. 629-638 
    ISSN: 1432-0878
    Keywords: Ciliary process ; Cultured explant ; Epithelial cells ; Ultrastructure ; Bovine and rabbit eyes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural characteristics of ciliary epithelium from bovine, pigmented rabbit, and fetal albino rabbit were studied in cultured explants. The tips of ciliary processes were cultured in plastic dishes with Dulbecco Modified Eagle Medium (DMEM) containing 5% fetal bovine serum. More than half of the expiants adhered to the plastic culture dish, and epithelial cells spread as monolayers within a few days. Initially the explant contains two layers, the outer (nonpigmented cells) and the inner (pigmented cells). Later the explant exhibits three layers: 1) outermost lightly pigmented flattened cells, 2) an outer layer of nonpigmented cells, and 3) an inner layer of densely pigmented cuboidal cells. The cells of the outermost layer are continuous with the cells of the inner layer. A narrow space lies between the outermost layer and the outer layer. The columnar cells in the outer layer contain well developed organelles but no pigment granules; they possess a basement membrane, lateral interdigitations, and junctional complexes near their apices. Numerous focal junctions and some ciliary channel-like structures were detected between the columnar cells of the outer layer and the cuboidal cells of the inner layer. The cuboidal cells of the inner layer are filled with pigment granules. These observations suggest that the columnar cells of the outer layer are nonpigmented epithelium, the cuboidal cells of the inner layer are pigmented epithelium, and the flatened cells in the outermost layer are derived from pigmented epithelium.
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  • 144
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    Cell & tissue research 233 (1983), S. 693-698 
    ISSN: 1432-0878
    Keywords: Thyroid gland ; Human fetus ; Follicles ; Ultrastructure ; Differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Thyroid glands from 40 human fetuses ranging from 30 to 175 mm in length were examined by electron microscopy. At the 30 mm stage, the cells are arranged in cords or clusters and contain numerous free ribosomes. The rough-surfaced endoplasmic reticulum (RER) is poorly developed and the Golgi complex consists of saccules, smooth and coated vesicles. Mitochondria, microfilaments, glycogen particles, occasional lysosome-like structures, and single cilia are observed. At sites of incipient follicle formation, intercellular clefts containing interdigitating microvilli, delimited by junctional complexes, are evident. In addition, the apical region of some cells contains vacuoles. At the 50-mm stage, intercellular clefts are more apparent, some of them organized into small follicles through the enlargement of the lumen, the incorporation of additional cells, and the formation of a basal lamina. With increasing gestational age, more follicles are established. The lumina vary from round to clover-leaf shaped and have an electron-dense content. Cisternae of RER are dilated and contain flocculent material. The Golgi complex is more extensive, and lysosome-like structures are more numerous. By the 100-mm stage, the follicular cells appear morphologically well differentiated. The results demonstrate an extracellular origin of the follicular lumen in the human fetal thyroid.
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  • 145
    ISSN: 1432-0878
    Keywords: Fibronectin ; Lung ; Development ; Ultrastructure ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In a previous study changes in the macrodistribution of fibronectin during rat-lung development were examined. Using the peroxidase-antiperoxidase immunocytochemical technique, we have demonstrated the presence of fibronectin in embryonic, neonatal, and adult rat lung at the ultrastructural level. In the embryo, fibronectin is found both in an intra-and extracellular association with isolated pneumoblasts, and in a periodic distribution along the basal lamina. The neonate displays fibronectin in an intracellular association with early type-I cells and on their basal and luminal surfaces, but not in association with type-II cells. Neonatal basal lamina is diffusely labeled by anti-fibronectin antiserum. Fibronectin in adult tissue is found both intracellularly and on the basal and luminal surfaces of type-I cells but not in type-II cells. The basal lamina and interstitial connective tissue are slightly or non-reactive. These observations confirm and extend our initial suggestion that fibronectin is involved in rat-lung development.
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  • 146
    ISSN: 1432-0878
    Keywords: Sea star ; Development ; Cuticle ; Extracellular materials ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of conspicuous extracellular materials during the life history of a sea star (Patiria miniata) is described. The outer surface of the developing sea star is covered by two morphologically different cuticles that appear sequentially during ontogeny. The primary cuticle, which is about 120 nm thick and two-layered, is present from mid-blastula through the end of the larval stage. The secondary cuticle, which is about 1 μm thick and three-layered, first appears on the epidermis of the rudiment region of the larva and, after metamorphosis, covers the entire epidermis of the juvenile and adult stages. During ontogeny, there are only two conspicuous gut cuticles: the first lines the newly invaginated archenteron at the start of the gastrula stage, and the second lines the esophagus during the larval stage. A blastocoelic basal lamina first appears at mid-blastula and persists as subectodermal and subendodermal basal laminae. Ruthenium red-positive granules are detectable between the lateral surfaces of adjacent ectodermal cells during part of the gastrula stage; this transient intercellular material may possibly aid in lateral adhesion between cells.
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  • 147
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    Protoplasma 114 (1983), S. 85-92 
    ISSN: 1615-6102
    Keywords: Chloroplasts ; Iron stress ; Sugar beet ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary When grown in iron-free media, the youngest leaves of healthy green sugar beet plants became completely yellow after 6 to 8 days. This chlorosis was quickly reversed by resupplying iron. A study of the ultrastructure of the iron -stressed leaves revealed apparently normal subcellular organization except for the plastids which were small and undeveloped, contained a rudimentary, disorganized grana-fretwork and clusters of vesicles in the periphery. Twelve to 16 hours after resupply of iron, aggregates of phytoferritin were observed in the stroma, and the granal fretwork underwent further development. There was an increased orientation of the membranes along the long axis of the plastids and an increase in the length of the individual grana stacks. By 48 hours, leaf chlorophyll content was about 40% of the control. At the ultrastructural level, parallel alignment of membrane orientation was complete and the grana stacks began to increase in the number of thylakoids per stack.
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  • 148
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    Protoplasma 115 (1983), S. 1-10 
    ISSN: 1615-6102
    Keywords: Brassica napus ; Nucleolus ; Pisum sativum ; Ultrastructure ; Zea mays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The karyosome is a spherical body up to 1 μm in diameter that lies on the nucleolus of certain plant species, particularly those with a relatively low nuclear DNA content and an areticulate nuclear structure. It can be seen in the light microscope after impregnation with silver; in the electron microscope its structure consists of fibrillo-granular material. Nucleoli of cells in root apices may bear 0, 1, or 2 karyosomes. The frequency with which these numbers of karyosomes are observed depends on the location of the cells within the apex. In roots ofPisum sativum andZea mays the nucleoli of both slowly-dividing and young differentiating cells bear karyosomes more frequently than the nucleoli of rapidly-dividing cells. The karyosome seems to adopt a preferred location on the nucleolus, lying most frequently on the nucleolar surfaces directed towards the apex or base of the root. The origin and functional significance of the karyosome are discussed. Morphological evidence suggests that it may be material that formerly was part of a fibrillar centre.
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  • 149
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    Protoplasma 116 (1983), S. 1-13 
    ISSN: 1615-6102
    Keywords: Cuticle ; Peristomatal transpiration ; Stomata ; Ultrastructure ; Funaria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Cuticle and pore development in the guard cells ofFunaria were investigated with the electron microscope. Pore cuticle formation is simultaneous with the creation of the pore itself. The morphology of the pore cuticle is unlike that of any cuticle described in the literature. It has many lamellae which are penetrated by electron dense fibrils. Three different cuticular morphologies exist from the pore to the subsidiary cell walls. The cuticles on the pore and outer walls contain fibrils that sometimes reach to the surface. The subsidiary cell cuticle lacks fibrils altogether. It is hypothesized that (1) cuticularization of the middle lamella contributes to ventral wall separation and (2) differences in extent of cuticular fibrils are related to greater water loss from stomata than from subsidiary cells (peristomatal transpiration).
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  • 150
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    Protoplasma 116 (1983), S. 115-124 
    ISSN: 1615-6102
    Keywords: Microtubules ; Moss ; MTOC ; Sporogenesis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Microtubule systems appear sequentially at the distal and proximal poles of tetrad members during mid-sporogenesis in the mossTetraphis pellucida Hedw. The distal microtubule system emanates from a microtubule organizing center (MTOC) located between the single plastid and the nucleus. The distal MTOC and associated microtubules, which appear immediately after cytokinesis, are ephemeral and do not appear to be associated with the deposition of exine occuring at the same time. The proximal microtubule system, which appears slightly later than the distal system, is a more stable component of mid-sporogenesis. The proximal MTOC is an irregularly lobed, patelliform aggregation of electron-dense granules located beneath the plasma membrane at the proximal spore pole. Several bundles of microtubules radiate from the proximal MTOC and traverse the cell, enclosing the nucleus in an cone of microtubules. The proximal microtubule system is thought to function in aperture development and organelle migration. The relatively large nucleus migrates a short distance in the small spore early in the tetrad stage and maintains its acentric position at the proximal pole throughout later stages of sporogenesis. The plastid migrates later in the tetrad stage from its meiotic position parallel to the distal surface to a position perpendicular to the distal surface with one tip in close proximity to the proximal MTOC. The proximal microtubule system reaches its maximum development by the end of the tetrad stage and all micrographic evidence of it is lost in the maturation stages of late sporogenesis.
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  • 151
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    Protoplasma 116 (1983), S. 99-114 
    ISSN: 1615-6102
    Keywords: Sphaerostilbe repens ; Ultrastructure ; Differentiation ; Coremia ; Rhizomorphs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The differentiating stages of coremia and rhizomorphs inSphaerostilbe repens were studied by transmission electron microscopy. Vegetative mycelium is characterized by highly cytoplasmic cells rich in ribosomes and mitochondria and with few vacuoles as well as endoplasmic reticulum. Cell walls are thin attaining a maximum thickness of 0.10 μm. During the aggregating phase a prosenchymatous mass of randomly oriented cells is produced by localized elongation and branching of the filaments. The hyphae in this region have the appearance of actively metabolising cells. In the course of the differentiating phase, numerous hyphae of the median zone of the aggregate grow upward and downward to give rise to coremium and rhizomorph primordia respectively. The individual hyphal tips lay parallel to each other and cells of the growing apices retain their meristematic characteristics. At the periphery of the aggregate and to a lesser extent in the subapical rhizomorphic zone, cells reduce their cytoplasmic density as a consequence of a decrease in the number of ribosomes. These cells also increase in size and become isodiametric and vacuolated. During cellular differentiation walls increase steadily in thickness and at the elongating phase they reach 0.30 μm in the rhizomorphic cortex. Mucilaginous material is progressively deposited around hyphae and in the most differentiated zones, coalesce to fill interhyphal spaces. This extracellular matrix seems to play a role in maintaining cohesiveness of the aggregated organs. The tissue in the process of differentiation is scattered with cells highly enriched in mitochondria and with cells virtually undifferentiated. Accumulation of microfilaments takes place in the differentiating zone localized behind the immersed meristematic apex. These structures might be involved in wall synthesis. Glycogen rosettes accumulate in the vegetative mycelium surrounding the aggregating centers, suggesting the possibility of supplying energy during the differentiating processes. The vacuolar system, represented by autophagic vacuoles which are present until the differentiation phase, presumably may also participate in the biochemical changes that occur during aggregation. Coremial cells are characterized by an increase in wall thickness, a highly sinuous plasma-membrane as well as large amounts of mucilaginous compounds accumulated between hyphae, but in all other respects they resemble the cells of actively growing vegetative hyphae.
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  • 152
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    Protoplasma 116 (1983), S. 125-135 
    ISSN: 1615-6102
    Keywords: Ciliated protozoan ; Sorogenesis ; Extracellular matrix ; Secretion ; Extrusive organelles ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Sorogena stoianovitchae Bradbury andOlive is an unusual kinetophragminophoran ciliate characterized by the aggregation of individual trophic cells to form a multicellular sorogen that rises aerially from the medium surface to produce a sorocarp. A light and electron microscope study of sorogenesis revealed how the sorogenic cells produce the stalk. The feeding ciliates contain numerous subpellicular expansions of rough endoplasmic reticulum cisternae that are only one element of the secretory system necessary for stalk formation. Upon aggregation, the stalk secretory system develops further, initially with the proliferation of the subpellicular expansions. Then, during later aggregation and early sorogenesis, other secretory elements appear: stalk material vesicles, dense granule vesicles, and electron lucent vacuoles. These are all derived from the rough endoplasmic reticulum. Only the subpellicular expansions and stalk material vesicles appear to add to the stalk matrix. The dense granule vesicles could be precursors of the stalk material vesicles; the electron lucent vacuoles, which can be demonstrated to contain fibrillar material, are perhaps by-products of the secretory process. Sorogenesis inSorogena occurs by a mechanism unique among the stalk-producing protists that have been studied.
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  • 153
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    Protoplasma 116 (1983), S. 136-144 
    ISSN: 1615-6102
    Keywords: Stalk ; Ciliated protozoan ; Sorogenesis ; Extracellularmatrix ; Ultrastructure ; Secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The sorogenic cells of the haptorid ciliateSorogena stoianovitchae Bradbury andOlive secrete a hydrated, fibrillar matrix that becomes organized to form a stalk. This light and electron microscope study examines the role of the secreted stalk matrix in the development of the sorocarp. The stalk material is secreted as a compact clump or clumps of material that expands as it hydrates. The expanded stalk material is initially viscous, but soon, through dehydration or cross-linking, solidifies to form a sheath. The sheath is the outside layer of the stalk, provides structural support, and controls the expansion of the newly secreted stalk material. The sorogenic cells continue to secrete stalk material that expands once it is outside of the cell. The resulting expansion force is directed upward by the sheath, thereby moving the cells further above the surface. The continued dehydration of the sheath material provides an inwardly directed force that also contributes to the upward movement of the sorogen.
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  • 154
    ISSN: 1615-6102
    Keywords: Cytochrome oxidase ; Cytochemistry ; Ultrastructure ; Neurospora ; Heat treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Cytochrome oxidase (EC 1.9.3.1) activity of conidia of wild-typeNeurospora crassa was detected cytochemically at the ultrastructural level by 3,′-diaminobenzidine (DAB) reaction during heat treatment at 46 °C and after shift down to 25 °C. At 46 °C the decrease in the enzyme activity was shown to be time-dependent (0–10 hours) in the progressively overswelling conidia. Gradual recovery of the DAB reaction occurred in mitochondria of conidia outgrowing conidiogenous germ tubes (microcycle conidiation) when shifted down to 25 °C. Inactivation of cytochrome oxidase was efficiently prevented during heat treatment in the presence of Tween 20. Such conidia no longer overswelled but still required shift down to 25 °C to produce germ tubes with delayed conidiogenous ability.
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  • 155
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    Protoplasma 117 (1983), S. 7-16 
    ISSN: 1615-6102
    Keywords: Beta vulgaris ; Chloroplast ; Ultrastructure ; Ultraviolet radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The effect of UV-C (254 nm) and UV-B (290–320 nm) radiation on leaves ofBeta vulgaris L. at the ultrastructural level was investigated. Although the damage caused by UV-C radiation was more striking than that resulting from UV-B radiation, several structural changes were seen in the UV-B treated material. Generally the effects of UV-B and UV-C radiation were different, suggesting different mechanisms of action, discernible even at the ultrastructural level.
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  • 156
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    Protoplasma 117 (1983), S. 116-129 
    ISSN: 1615-6102
    Keywords: Pollen ; Amoeboid tapetum ; Arum italicum ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A tapetum is found around all higher plant meiocytes and is thought to nourish them. It may, in turn, be influenced by their development. The mature tapetal membrane in amoeboid (or periplasmodial) tapeta, of whichArum italicum is an example, fits closely around the developing meiocyte. This description of tapetal ultrastructure starts from the meiotic prophase when the tapetum is still cellular and comprises two rows of cells on the inside of the tetrasporangiate anther. The radial walls of the still cellular tapetum start to dissolve during leptotene of the first meiosis. The lysis begins in the middle lamella in those areas penetrated by the most plasmodesmata. The walls in contact with the meiocytes on the other hand do not disappear until after the first meiosis. At telophase the now fused cytoplasmic tapetal mass begins to extend its joint plasmamembrane, amoeboid fashion, into the loculus. A cluster of microtubules can be seen at the apex of this intrusion apparently initiating or maintaining the shape of the invading plasmamembrane front. The tapetum now adheres closely to the microspores. The tapetal zone closest to the spores has a prominent population of microtubules and just a little ER, whereas the outer zone away from the spores contains all the other organelles. The inner zone, in a squash preparation, is not readily separated from the spores. The microtubules, at the middle microspore stage, are no longer to be seen in a circle around the microspores, but spread out with some lying orthogonal to the now-forming exine surface. In places the tapetal plasmamembrane begins to retract from the exine leaving roughly cone-shaped zones (spines) which become filled with fibrillar material. This material begins to be deposited on the exine surface. These “spines” are both PAS. and Coomassie-blue positive and susceptible to acetolysis.
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  • 157
    ISSN: 1615-6102
    Keywords: Histochemistry ; Sclerotia ; Sclerotial germination ; Sclerotinia ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Cytoplasmic reserves and extracellular substances were progressively broken down and utilized during carpogenic germination of sclerotia ofSclerotinia minor. Glycogen, wall polysaccharides and polyphosphate granules were removed first from regions of the sclerotium distant from developing apothecia, while protein bodies near the base of apothecial stipes were hydrolysed before those further away. The number of profiles of mitochondria and endoplasmic reticulum in cortical and medullary hyphae increased at the onset of germination, indicating increased metabolism in the hyphae. In contrast to developing sclerotia, simple pores with Woronin bodies were frequent in walls and septa during germination. Hyphae that appeared to converge towards the base of apothecial initials retained their cytoplasm and organelles until late in germination and hydrolysis of their reserves was delayed; these are interpreted as translocatory hyphae, although further work is required to determine their role unequivocally. When apothecia were fully developed, hyphae throughout the sclerotium were empty and the walls and extracellular matrix of cortical and medullary hyphae had almost completely broken down.
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  • 158
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    Protoplasma 118 (1983), S. 56-70 
    ISSN: 1615-6102
    Keywords: Carposporophyte ; Cell division ; Mitosis ; Rhodophyta ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Mitotic ultrastructure was observed in meristematic cells of carposporophyte generations of the freshwater red algaBatrachospermum ectocarpum. Prior to nuclear division, cell elongation occurs resulting in the nucleus being located at the proximal end of the cell and separated by a large central vacuole from a distal “empty region” which the daughter nucleus eventually occupies. In late prophase, nuclear envelope-attached polar rings are situated adjacent to shallow nuclear invaginations. At prometaphase the nuclear invaginations extend deeply into the nucleus forming continuous cytoplasmic channels containing microtubules. Perinuclear ER and a typical equatorial chromosomal plate are formed by metaphase at which time the nuclear envelope lining the cytoplasmic channels has dispersed. Chromosomal and non-chromosomal microtubules converge at the poles where a single, large gap is seen in the otherwise intact nuclear envelope. Polar rings were not detected in the few mitotic cells observed beyond prometaphase but are thought to be present. During anaphase an interzonal midpiece is formed and the distal-most incipient daughter nucleus moves laterally past the central vacuole into the apical “empty region”. Features of mitosis inBatrachospermum are believed to be intermediate between those exhibited by the lower and higher orders of red algae, this being consistent with the taxonomic placement of the genus in theNemaliales, the least advanced order of the classFlorideophyceae.
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  • 159
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    Protoplasma 118 (1983), S. 95-103 
    ISSN: 1615-6102
    Keywords: Nuclear bodies ; Nucleolus ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Nuclear bodies are found in interphase nuclei of root apices of a number of plant species. They often show differences in structure and position relative to the nucleolus and this has led to an attempt to define two classes of body. However, in some species their separation into two classes on structural grounds alone breaks down, indicating that although they may occupy different positions within the nucleus they may in these particular cases be only different forms of the same body. The two extremes of the range of bodies examined represent what have been called “nucleolus-associated body” (karyosome) and “dense body”. The nucleolus-associated body is typically attached to, or adjacent to, the nucleolus. It is composed of fibrils 4–8 nm wide and often has an open structure showing compound threads or fibrils separated from each other by electron-lucent spaces. The dense body is more compact in structure and typically lies free in the nucleoplasm. Both types of body have an affinity for silver ions which, together with their staining reaction following treatment with EDTA, indicates that they consist of ribonucleoprotein. The characteristics of nuclear bodies found in different plant species have some relationship with the structure and DNA content of the interphase nucleus. Nucleolus-associated bodies are characteristic of species with an areticulate nuclear structure (2 C DNA content 〈6 pg), while dense bodies are common in species with a reticulate nuclear structure (2 C DNA content 〉6 pg). The possible functions of the two forms of nuclear body are discussed.
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  • 160
    ISSN: 1615-6102
    Keywords: Calcification ; Coccolithophorids ; Polysaccharide localization ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Emiliania huxleyi is a marine coccolithophorid which produces coccoliths,i.e., particles consisting of calcite and macromolecular organic material. The coccoliths are formed intracellulary in specialized organelles which comprise a coccolith vesicle (CV) and a reticular body (RB), together forming the CV/RB system or calcifying system. After termination of calcification, the coccolith is extruded and incorporated into the coccosphere,i.e., one or several layers of extracellular coccoliths surrounding the cell. Apart from the coccolith-producing cells (C cells) ofE. huxleyi, there are naked cells (N cells) which seem to have lost the capacity to produce coccoliths but are very similar to the C cells in other morphological respects. Biochemical studies have revealed that polysaccharides may play a regulatory role in calcification. The aim of the present study was to determine the localization of polysaccharides in both C and N cells electron microscopically. For this purpose, a cytochemical staining technique according toThiéry (1967) was applied. The CV/RB system of C cells was conspicuously stained. Due to the excellent stainability of this system, a putative succession of morphological stages during coccolithogenesis could be described. The staining pattern of the N cells closely resembled that of the C cells. It was found, however, that the “calcifying” system of N and C cells differed in both morphology and position. It is suggested that the divergent morphology of the “calcifying” system of N cells accounts for its failure to produce coccoliths.
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  • 161
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    Investigational new drugs 1 (1983), S. 47-58 
    ISSN: 1573-0646
    Keywords: dihydro-5-azacytidine ; DHAC ; pharmacokinetics ; clearance ; foxhound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The decline in DHAC plasma concentrations was greater than three log decades after dosing. The plasma concentration-time data was computer-fitted by NONLIN to a three compartment open model with first-order elimination using the equations for a short intravenous infusion. The half-lives corresponding to the three exponential phases were: t1/2α =5.78 min, t1/2β =1.57 h and t1/2γ =22.0 h in dog 1 and t1/2α =7.41 min, t1/2β =2.25 h and t1/2γ =21.6 h in dog 2. The terminal phase of the plasma concentration time profiles represented a minor contribution (2.2–3.2%) to the total area under the curve. The plasma concentration time data for the first 12 h after dosing was computer fitted to a two compartment open model. The initial and terminal half-lives determined from the two compartment fits were similar to the t1/2α and t1/2β values of the fits to the three compartment open model. Similar total body clearance values were calculated from the areas under the plasma concentration time curves from time zero to infinity for the computer fits to the three and two compartment models, respectively. Thus, for practical purposes, it appears feasible to define adequately the total body clearance of DHAC by analysis of the plasma concentration time data during the time interval in which the plasma concentration is described as a bi-exponential equation. Renal excretion of the parent drug is the principal route of excretion of DHAC from the dog.
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 499-513 
    ISSN: 1573-8744
    Keywords: methotrexate ; 7-hydroxy-methotrexate ; pharmacokinetics ; nonlinear pharmacokinetics ; dose-dependent pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX), a major metabolite, were investigated in rabbits after intravenous bolus injection and infusion using a specific HPLC assay. The arterial sampling (from the carotid artery) was used in all the studies since peculiar and significant arterial-venous differences in the plasma concentration of MTX and 7-OH-MTX were found following bolus administration of the drug. The disposition kinetics of MTX appeared polyexponential with a small terminal phase having a half-life of 10.2–27.5 hr. Extensive formation of 7-OH-MTX occurred at the two dose levels (15 and 50 mg/kg). Nonlinear disposition of MTX was reflected in several aspects of data analysis. A disproportionate increase in the AUC with dose was observed. An increase in dose not only reduced the mean total body clearance (7.49 vs. 4.26 ml/min/kg) and renal clearance (4.89 vs. 2.76 ml/min/kg), but also prolonged the mean residence time (26.2 vs. 43.3 min). The steady-state volume of distribution (Vss) of MTX was estimated to range from 0.16 to 0.25 L/kg. More than 90% of the dose was excreted as MTX and 7-OH-MTX within 8 hr after dosing. Renal clearances decreased with the increasing plasma levels, suggesting active tubular secretion as one of the excretion mechanisms. A similar pattern for renal clearance of 7-OH-MTX was obtained. Infusion studies of 7-OH-MTX revealed that this metabolite had a longer residence time and a larger Vss as compared with MTX, which were in accordance with its physicochemical properties. Essentially complete doses of 7-OH-MTX could be recovered in the rabbit urine.
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  • 163
    ISSN: 1573-8744
    Keywords: insulin ; continuous subcutaneous infusion ; plasma immunoreactive insulin ; pharmacokinetics ; preprogrammable infusion pump ; reconstruction of predetermined plasma insulin profiles ; dogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A preprogrammable insulin delivery system which can provide the flexibility of varying plasma insulin concentration in a physiological manner has been developed. This system involves a program of continuous subcutaneous infusion of insulin at variable rates to reproduce arbitrarily selected plasma insulin concentration-time profiles. The desired insulin infusion rate profile was calculated from the desired insulin pattern using pharmacokinetic parameters experimentally determined by measurement of immunoreactive plasma insulin following a subcutaneous bolus dose to depancreatized dogs.
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  • 164
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 289-301 
    ISSN: 1573-8744
    Keywords: parameter estimation ; upper and lower bounds ; pharmacokinetics ; initial estimates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The upper and lower bounds of rate constants for general mammillary three and four compartment systems have been derived. It is further proposed that the midpoints of the bounds can be used as initial estimates for parameter estimation. Numerical examples are given demonstrating the closeness of the calculated midpoints to the “known” rate constants of both the three and four compartment systems.
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  • 165
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 561-576 
    ISSN: 1573-8744
    Keywords: methylprednisolone ; bioavailability ; pharmacokinetics ; oral and parenteral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This study was conducted to evaluate the influence of route of administration upon the bioavailability and pharmacokinetics of methylprednisolone sodium succinate. Fourteen healthy adult male volunteers received 40 mg doses of methylprednisolone as the following treatments after an overnight fast in a 4-way crossover design: (a) as a 1 ml i.v. bolus;(b) as a 1 ml i.m. injection;(c) administered as an oral solution;and (d) as 5×8 mg oral tablets. Both the ester and free methylprednisolone were determined in plasma and urine. Study results indicate that the ester is rapidly and extensively converted to free methylprednisolone after all routes. The extent of methylprednisolone absorption was equivalent after i.v. and i.m. administration. Both orally administered treatments resulted in a lower extent of absorption attributed to a first-pass effect. Although a slightly lower extent of absorption was demonstrated following the oral administration of the methylprednisolone sodium succinate solution relative to the methylprednisolone oral tablets, this average difference of 9% would probably be of minimal therapeutic importance.
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  • 166
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 183-187 
    ISSN: 1573-8744
    Keywords: nonlinear regression ; parameter estimation ; invariance ; transformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract It is shown that when one nonlinear regression model is a reparametrization of a second model, the parameter estimates, and their standard errors, for one model can be obtained directly from those obtained from fitting the other model.
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  • 167
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 389-400 
    ISSN: 1573-8744
    Keywords: time-dependence ; volume of distribution ; curve-fitting ; simulations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present study was conducted to develop, test, and apply a simple exponential time-dependent volume of distribution function to describe the pharmacokinetics of compounds following instantaneous, zero-order and first order input. Simulations were used to show the applicability and flexibility of the equations. Experimental data from the literature were fitted using the equations developed in the present study. In addition, the results of these fitted curves were compared to the results of the original fitting procedures to compare and contrast the methods. In the present analysis, the change from an initial volume (V1)to the total volume (VT)is perceived as a simple exponential function. Therefore, a single exponential term to describe elimination and a single exponential term to describe the change from V1 to VT were used to describe the entire blood concentration profile. The results from present simulations and fitted data indicate that the transition from V1 to VT is a more continuous process than observed with classical methods and is consistent with results obtained from physiologic flow-limited models. This observation suggests that the present curve-fitting technique may be more akin to physiologic reality, in that it depicts the change from the initial volume of distribution to the total volume of distribution as a continuous exponential function which reflects the establishment of an equilibrium.
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  • 168
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 31-46 
    ISSN: 1573-8744
    Keywords: bumetanide ; probenedd ; pharmacokinetics ; pharmacodynamics ; doseresponse relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium, excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.
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  • 169
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    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 47-61 
    ISSN: 1573-8744
    Keywords: d-tubocurarine ; pharmacokinetics ; pharmacodynamics ; multicompartrnent model ; Hill equation ; plasma ; tibialis anterior muscle ; protein binding ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract After bolus intravenous dosing of d-tubocurarine (d-TC) to rats, the twitch heights of the tibialis anterior muscle indirectly stimulated were followed, and its decrease was defined as pharmacologic response of d-TC. The relation between dose and response intensity was found to be well described with Hill's equation. According to a theory proposed by Smolen, Hill's equation was also applicable to the biophase d-TC concentration-response relation; the time courses of the relative biophase d-TC concentration indicated linear kinetics with dose levels ≤0.15 mg/kg and the occurrence of dose-dependent disposition with 0.30 mg/kg. After bolus i.v. dosing of3H-d-TC, plasma d-TC concentration obeyed a dose-independent two compartment model with doses ≤0.15mg/kg, but not with 0.30 mg/kg. This finding matched the above estimated with pharmacologic data. The active metabolite was not found in plasma and urine. The extent of d-TC plasma protein binding was independent of the wide range of plasma levels and its mean (±SD) value was 30.5 (±3.8). Plasma d-TC levels and pharmacologie response intensity were well correlated by Hill's equation and a three compartment model (the general two and the biophase compartments) in the dose range ≤0.15 mg/kg.
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  • 170
    ISSN: 1573-8744
    Keywords: naltrexone ; controlled release ; pharmacokinetics ; gas chromatography ; biodegradable copolymer delivery system ; release rate quantitationin vivo ; Loo-Riegelman method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Naltrexone release rates from a controlled release delivery system have been quantitated over a time period greater than one month in the monkey. The method requires calibration of the pharmacokinetic parameters of each monkey utilizing an intravenous bolus dose and assay of unchanged naltrexone levels in plasma as a function of time after dosing. Also required are periodic plasma levels of unchanged naltrexone obtained subsequent to administration of the delivery system. Release rates are then calculated as well as the total amount released. Application of the methodology to a biodegradable copolymer naltrexone delivery system in three monkeys showed an initial release rate of 3– 8% of the dose per day over the first 3– 5 days followed by a slow, rather constant release rate of 1– 3% per day from day 5 to the time of the last measurable plasma sample (36– 43 days). Comparison of alternative calculation methods using both experimental and simulated plasma naltrexone data verified the accuracy of the release rate calculations. The sum of the calculated total amount of naltrexone released plus the assayed amount remaining in the delivery system after removal from the animal accounted for 91– 94% of the administered dose in the two monkeys in which complete data were obtained.
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  • 171
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    Plant and soil 71 (1983), S. 147-153 
    ISSN: 1573-5036
    Keywords: Cortex ; Endodermis ; Picea sitchensis ; Tilia cordata ; Transfer cells ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The endodermis of bothTilia cordata andPicae citchensis progressess through 3 characteristic phases of development. These developments are delayed somewhat in the xylem pole endodermis ofT. cordata, while inP. sitchensis 3–5 passage cells are found. The cortex ofT. cordata is characterised by very thick walls, while that ofP. sitchensis is characterised by a thick walled layer just outside the endodermis and by 2–3 outer layers of transfer cells.
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  • 172
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    European archives of oto-rhino-laryngology and head & neck 238 (1983), S. 205-208 
    ISSN: 1434-4726
    Keywords: Teflon granuloma ; Vocal cords ; Multinucleate giant cells ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural characteristics of multinuclear foreign-body giant cells (MCG) in a human vocal cord Teflon granuloma are described. The cells were found to contain varying numbers of Teflon particles within their cytoplasm. The particles, rounded or oval in shape, were surrounded by a rather elctron-dense membrane. Numerous lysosomal structures were discerned within the cells. The fine structure of MCG in granulomas induced by foreign materials other than Teflon has already been described in man as well as in several experimental animals, and the Teflon MCG resembled these cells in many respects. No evidence of malignant change was found.
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  • 173
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    Acta applicandae mathematicae 1 (1983), S. 105-120 
    ISSN: 1572-9036
    Keywords: Systems ; control ; Biomathematics ; identification in compartmental systems ; compartmental models ; pharmacokinetics ; optimal control of drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract We first introduce some main problems in pharmacokinetics and then we propose methods for their resolution. Of course, identification problem is considered. A numerical efficient method is given. It brings back to the resolution of a succession of linear algebraic systems. In the case of non unicity we suggest an approach based on the adjunction of a criterion to minimize. The last part studies the optimal injection of a drug associated to an optimization criterion. An explicit solution can be found for a n-compartments linear system.
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  • 174
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    Cell & tissue research 228 (1983), S. 205-218 
    ISSN: 1432-0878
    Keywords: Spermatozoa ; Ultrastructure ; Deep-freezing ; Sperm manipulation ; Trout
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Trout spermatozoa taken from the testis, vas deferens and ejaculate are described at the ultrastructural level. The morphology of the spermatozoa head, changes in the middle-piece structure, and the relationship between the centrioles and the flagellum were studied under consideration of their role in the reproduction of this species. Morphological changes observed after dilution of the spermatozoa in freshwater or saline and subsequent freezing deserve attention in connection with certain manipulations used in fish farms and laboratories.
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  • 175
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    Cell & tissue research 228 (1983), S. 231-244 
    ISSN: 1432-0878
    Keywords: Pineal gland ; Circadian rhythm ; Synaptic ribbon ; Ultrastructure ; Chinese hamster (Cricetulus griseus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Circadian morphological variations of pinealocytes in the superficial pineal of the Chinese hamster (Cricetulus griseus) were studied using quantitative electron-microscopic techniques. The volume of the nucleus and cytoplasm of pinealocytes exhibited similar circadian variations, with the maximum around the middle of the light period and the minimum during the first half of the dark period. Synaptic ribbons in pinealocytes were classified into three groups, type-1, −2 and −3 synaptic ribbons, which appeared as rods, round or irregular bodies and ring-shaped structures, respectively; a synaptic ribbon index was determined for the respective types. The synaptic ribbon index was expressed as the number of synaptic ribbons in the pinealocyte profile representing the cell size. The type-1 synaptic ribbon index, which was smallest during the second half of the light period, was increased during the dark period. The length of straight or slightly curved rods showed a 24-h change similar to that of the type-1 synaptic ribbon index; the length of the rods was maximal during the first half of the dark period and minimal at the end of the light period. There was no apparent circadian variation in the type-2 synaptic ribbon index. The type-3 synaptic ribbon index was higher during the light period than during the dark period; the index attained zero 3h after the onset of darkness and, thereafter, increased gradually.
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    Cell & tissue research 228 (1983), S. 265-276 
    ISSN: 1432-0878
    Keywords: Met- and leu-enkephalin ; Immunocytochemistry ; Ultrastructure ; Lateral septum ; Guinea-pig brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary By the use of antisera to met-enkephalin and leu-enkephalin, enkephalin-containing structures were visualized in the lateral septum of the guinea-pig brain. The present results do not reveal immunoreactive perikarya in this area. The immunostaining is exclusively located in numerous nerve fibers and endings mostly encompassing neuronal perikarya, which accounts for the fact that at the light-microscopic level cellular somata appear to be immunostained. The immunoreactive terminals and fibers contain granules approximately 110nm in diameter and synaptic vesicles. The origin and the functional role of these numerous enkephalin terminals remain to be established. This work was supported by a grant from INSERM N∘ 804012
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  • 177
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    Cell & tissue research 228 (1983), S. 323-335 
    ISSN: 1432-0878
    Keywords: Ultrastructure ; Colonic epithelium ; Colchicine ; Vesicles ; Glycoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In murine colonic epithelial cells, cell-coat glycoproteins are transported to the cell surface in vesicles that originate at the Golgi apparatus. To determine the role of microtubules in the movement of these vesicles the antimicrotubule agent colchicine was injected into mice at several time intervals prior to sacrifice. In the mice that were treated with colchicine for 4.5 h it was observed that the polarity of the cells was disturbed. The Golgi apparatus and nucleus often appeared interchanged in their positions. The glycoprotein-containing vesicles, normally located apically, were sparse in that location, but abundant near the lateral plasma membranes of the cells at the level of the nucleus and Golgi apparatus. Staining by the periodic acid-chromic acid-silver methenamine technique for glycoproteins clearly revealed the reduction of vesicles apically and accumulation of vesicles laterally. The mechanism responsible for the movement of the vesicles to this location is unclear. It is suggested that the accumulation of vesicles in the lateral region may reflect some hindrance in the fusion of the vesicles with the lateral cell membranes.
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  • 178
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    Keywords: Lymph nodes ; Postnatal development ; Fibroblastic reticulum cells ; Interdigitating cells ; Deep cortex units ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This study describes the postnatal development of the nonlymphoid cells with special reference to the fibroblastic reticulum cells (FRCs) and interdigitating cells (IDCs). The first lymphocytes of the neonatal lymph nodes are located in the developing deep cortex units (DCUs) identified by the Gomori's technique for reticulin fibres. Ultrastructural studies demonstrate that FRCs form the stroma of the DCUs. By light and electron microscopy, it is demonstrated that FRCs occupy the outer cortex in the following stages of development of the lymph nodes. Thus, FRCs form the stroma of the primary follicles and, later, are transformed in follicular dendritic cells (FDCs) of the germinal centres. Immature or pro-IDCs appear as migrating elements in the deep cortex of lymph nodes of the neonatal rats. The ultrastructure of the pro-IDCs resembles that of the mature IDCs but not that of the phagocytic cells. Pro-IDCs are transformed into mature IDCs whose cytoplasmic expansions contact lymphocytes via tight junctions. Some of these lymphocytes are likely apposed to FRCs of the DCUs. No cells containing Birbeck granules were found in the parenchyma of the lymph nodes during the postnatal development. The role of these nonlymphoid cells is discussed with respect to the immunologic function of mammalian lymph nodes.
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  • 179
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    Cell & tissue research 229 (1983), S. 281-297 
    ISSN: 1432-0878
    Keywords: Paraventricular nucleus ; Hypothalamus ; Development ; Golgi study ; Ultrastructure ; Chick embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The developmental changes in the cytoarchitecture of the hypothalamic paraventricular nucleus of the chick embryo were studied with particular emphasis on the differentiation of the magnocellular neurons. These cells can be distinguished from the parvocellular elements starting from stages 34–35 (Hamburger and Hamilton 1951) in Golgi-impregnated specimens. At the same stages, electron microscopy reveals dense-core granules, resembling the characteristic elementary granules of the neurosecretory material in the cytoplasm of the larger neurons. In addition, a few immature synapses were observed on these magnocellular perikarya. The present observations suggest that the early onset of neurosecretion in this area may be neurally regulated during early phases of development.
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  • 180
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    Cell & tissue research 231 (1983), S. 663-674 
    ISSN: 1432-0878
    Keywords: Ciliary tuft ; Pallil tentacles ; Patella vulgata ; Sensory ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The structure and ultrastructure of ciliary tufts on the pallil tentacles of the limpet Patella vulgata (L.) are described. The tip of each tentacle is covered by a dense crown of tufts and additional tufts can be seen scattered evenly across the surface of each tentacle. The cilia are nonmotile and nerve fibres run from the base of the ciliated cells suggesting a sensory function. Comparisons are made with ciliary tufts found in a Pacific species of limpet, Acmaea scutum, and other molluscan sensory structures.
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  • 181
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    Keywords: Pregnancy ; Adrenal zona glomerulosa ; Juxtaglomerular apparatus ; Ultrastructure ; Sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular apparatus have been examined during normal pregnancy in sheep. As pregnancy progressed, increasing numbers of cells in the adrenal zona glomerulosa displayed mitochondria with straight tubular “rod-like” structures replacing their normal lamelliform cristae; groups of cells showing these mitochondrial changes were predominantly located in the middle and superficial regions of the zona glomerulosa, but at all stages remained interspersed with cells with apparently normal mitochondria. In the same animals, the renal juxtaglomerular index was raised, reflecting an increase in renin storage, and juxtaglomerular myoepithelioid cells showed increased numbers of cytoplasmic granules, but no apparent increase in granular endoplasmic reticulum and Golgi profiles; there were no distinguishing morphological changes in juxtaglomerular peripolar cells. These findings provide morphologic evidence of stimulation of the adrenal zona glomerulosa in association with increased juxtaglomerular renin storage during pregnancy. The mitochondrial changes observed in an increasing proportion of cells in the zona glomerulosa closely resemble those seen in sodium-depleted animals, and may reflect the altered steroidogenic capacity of the adrenal gland in pregnant sheep. The finding of groups of cells displaying altered mitochondria lying next to cells with normal mitochondria suggests the presence of cells with different sensitivities to stimuli for aldosterone production or may indicate the presence of different cell types in the zona glomerulosa responding to different stimuli.
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    Cell & tissue research 234 (1983), S. 365-376 
    ISSN: 1432-0878
    Keywords: Oesophageal striated muscle ; Ultrastructure ; Guinea-pig, marmoset
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural characteristics of oesophageal striated muscle from guinea-pig and marmoset have been examined using transmission electron microscopy and compared with ultrastructural features of skeletal muscle. The findings show that, although similar to skeletal muscle, oesophageal striated muscle exhibits important differences in the arrangement of its muscle fibres and their motor innervation. It was also found impossible to classify oesophageal striated muscle according to the usual ultrastructural criteria since its motor endplates bore a greater resemblance to those of intrafusal skeletal muscle fibres. The consideration of these differences in conjunction with characteristics revealed elsewhere by other techniques confirms the unique nature of oesophageal striated muscle.
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    Cell & tissue research 229 (1983), S. 155-174 
    ISSN: 1432-0878
    Keywords: Pituitary ; Tammar wallaby ; Marsupialia ; Ultrastructure ; Immunohistochemistry ; Cell types
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An immunohistochemical, light- and electron-microscopial study was made of the pars distalis in adult tammar wallabies (Macropus eugenii). The pars distalis of this marsupial mammal was divided into three regions, based on the distribution of cell types within the gland. Somatotropic, mammotropic, luteotropic, folliculotropic, corticotropic and thyrotropic cells were identified on the basis of their immunohistochemistry, cytology and ultrastructure. Non-granulated (folliculo-stellate) cells, identified in electron micrographs, were found throughout the pars distalis. Somatotropic cells were predominant in the posterior pars distalis in all animals examined. In the single male specimen and in the non-lactating females examined, small numbers of apparently inactive mammotropic cells were scattered throughout the pars distalis; the same cell type was apparently active and present in considerable numbers in lactating females. Only one morphological type of gonadotropic cell was evident; these cells were scattered throughout the pars distalis, but in largest numbers in the median region. Small numbers of thyrotropic cells were found, most commonly in the anterior pars distalis. Corticotrops were also observed in moderate numbers, predominantly in the anterior regions of the pars distalis.
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    Cell & tissue research 228 (1983), S. 313-322 
    ISSN: 1432-0878
    Keywords: Olfactory ; Sensilla ; Ultrastructure ; Insects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Scanning- and transmission electron-microscope studies of the sensilla of the pedicel of Nilaparvata lugens have revealed an elaborate plaque organ and three structurally different types of trichoid hairs. Each plaque organ is innervated by 120–150 neurons arranged in groups. The porous sensory cuticle is folded into finger-like projections and is surrounded by protective non-sensory denticles. Trichoid sensilla differ in number of neurons, appearance of dendrites and arrangement of pores. Type I, innervated by 2 neurons, has pores along its length and is probably olfactory in function. Types II and III are innervated by one and five neurons, respectively, and the absence of pores along the hair shaft indicates a possible gustatory role. The importance of these sensilla is discussed with reference to the behaviour of this important insect pest.
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    Cell & tissue research 228 (1983), S. 389-403 
    ISSN: 1432-0878
    Keywords: Lymph node, avian ; Ultrastructure ; Macrophages ; Phagocytic capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The structure of the avian lymph node (ALN) is characterized by a thin capsule, thin lymphoreticular cords, and an absence of trabeculae. It is not possible to subdivide the ALN into cortex, paracortex and medulla, or to subdivide the system of sinuses into marginal, trabecular and medullary divisions. The lymphoreticular cords contain avian germinal centers (AGC) with B-lymphocytes and the area of T-lymphocytes. Postcapillary venules are responsible for the recirculation of lymphocytes. Sinus reticular cells do not exist in the ALN, but free macrophages are present. The phagocytic capacity of the macrophages was determined by injection of vital dyes (India ink, Berlin blue) and inoculation with Candida cells. Macrophages filled with markers migrate from the lymph sinuses into the lymphoreticular cords and further into the AGC. The mobility of the macrophages is remarkably lower after phagocytosis of Candida cells.
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    Cell & tissue research 229 (1983), S. 299-308 
    ISSN: 1432-0878
    Keywords: Adrenal chromaffin cells ; Plasticity ; Transplants ; Kidney capsule ; Ultrastructure ; Catecholamine biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Histochemical, ultrastructural and biochemical studies (quantitative determinations of catecholamines (CA) and phenylethanolamine N-methyltransferase (PNMT) activity) were carried out on autologous transplants of adult guinea-pig adrenal medulla under the kidney capsule, in order to investigate the specific influences of a virtually nerve-free environment in comparison to those mediated by a densely innervated one such as in the iris (cf. Unsicker et al. 1981). Three weeks after transplantation chromaffin cells survived well, most cells maintaining their morphological identity in terms of adrenaline (A) storage, although biochemically measured A and PNMT had dramatically decreased. Chromaffin cells in transplants extended neurite-like processes in an identical fashion as seen in transplants to the anterior chamber of the eye and in culture. Chromaffin cells were frequently connected by synaptoid contacts, but did not receive cholinergic synapses as observed in transplants to the iris. It may be concluded that the growth factor(s) eliciting neurite outgrowth from transplanted chromaffin cells are rather ubiquitously present, independent of whether the transplantation site is sparsely or richly innervated.
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  • 187
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    Keywords: Adrenal zona glomerulosa ; Ultrastructure ; Sodium depletion ; Sodium loading ; Sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of alterations in sodium status upon the morphology of the adrenal zona glomerulosa in sheep have been examined qualitatively and quantitatively, using lightand electron microscopy, and correlated with functionally related biochemical data. With severe sodium depletion induced by parotid-cannula drainage, there was mitotic activity throughout the zona glomerulosa, and glandular cells showed striking ultrastructural changes. These changes particularly affected mitochondria, which were enlarged, rounded and showed replacement of their normal lamelliform cristae by thin elongated cristal elements and bundles of tubular “rod-like” structures. Quantitative morphometric studies showed an increase in the volumes of zona glomerulosa cells, nuclei, mitochondria, smooth and granular endoplasmic reticulum, and Golgi profiles. In contrast, with dietary sodium loading, zona glomerulosa cells appeared shrunken and showed cytoplasmic lipid accumulation; mitochondria and other organelles were not significantly altered. The correlation of the ultrastructural cytological alterations in zona glomerulosa cells in sodium-depleted sheep with raised blood aldosterone levels suggests that such morphologic changes reflect a heightened capacity of these cells for aldosterone biosynthesis and secretion. These changes may also account for the increased sensitivity of the zona glomerulosa to aldosterone-producing stimuli during sodium deficiency.
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    Cell & tissue research 229 (1983), S. 611-625 
    ISSN: 1432-0878
    Keywords: Spermatozoa ; Ultrastructure ; Pseudomys (Muridae, Rodentia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Sperm morphology among the various members of the genus Pseudomys showed great interspecific variation. In P. apodemoides, P. desertor, P. fumeus, P. gracilicaudatus, P. hermannsburgensis, P. higginsi and P. nanus the sperm head was bilaterally flattened and possessed three hooks, the length of which varied somewhat between species. The top hook contained nuclear, subacrosomal and acrosomal material, whereas the two lower ventral hooks displayed largely only an extension of the subacrosomal material. Four other species of Pseudomys had no ventral hooks in their sperm head. In P. novaehollandiae there was a single long top hook, whereas in P. pilligaensis it was almost nonexistent. Neither the sperm head of P. delicatulus, nor that of P. shortridgei possessed any hooks; the former became narrower towards the tip, whereas the latter was spatulate in shape. The acrosome covered about two thirds of the nucleus and varied considerably in shape between species. Insertion of the connecting piece of the tail occurred on the lower ventral side of the sperm head in all species with a long top hook but was nearly basal in P. delicatulus and midbasal in P. shortridgei. The ultrastructure of mid and principal pieces was similar among species, but the number of gyres of mitochondria ranged from about 64 to 100.
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  • 189
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    Cell & tissue research 230 (1983), S. 353-366 
    ISSN: 1432-0878
    Keywords: Homoptera ; Labium ; Sensilla ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the sensory receptors located on the labium of the rice brown planthopper is described; possible functions of individual receptors are suggested on morphological grounds. Uniporous chemosensilla which may or may not possess a mechanoreceptive dendrite, domed multiporous chemosensilla, and mechanoreceptive pegs are present on the flattened labial tip. Mechanoreceptive pegs are distributed over the labium. The fine structure of a multilobed sensillum located on either side of the labium is also described.
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  • 190
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    Cell & tissue research 233 (1983), S. 59-67 
    ISSN: 1432-0878
    Keywords: Pineal gland ; Synaptic ribbon ; Melatonin ; Ultrastructure ; Chinese hamster (Cricetulus griseus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of melatonin on synaptic ribbons (SR) in pinealocytes of the Chinese hamster (Cricetulus griseus) were examined. SR were classified into types 1, 2 and 3, which appear as rods, round or irregular bodies and ring-shaped structures, respectively; a synaptic ribbon index (SR index) was determined for the three types. Administration of two doses of 1.5 mg/kg melatonin at noon and 3 p.m. causes an increase in the type-1 and type-2 SR indices 3 h after the second injection in hamsters kept under alternating light and dark conditions (lights on from 7 a.m. to 7 p.m.). Likewise, in animals that are exposed to extended light for 6 h and receive two doses of melatonin at 7 p.m. and 10 p.m., an increase in the type-1 and type-2 SR indices occurs 3 h after the second injection. The increase in the type-2 SR index induced by melatonin administration to hamsters exposed to extended light is greater than the increase in the type-1 SR index under the same experimental conditions. Type-2 SR index, but not type-1 SR index, increases following bilateral superior cervical ganglionectomy. An increase in type-1 and type-2 SR indices occurs at 6 p.m. in ganglionectomized animals administered two doses of melatonin 6 h (noon) and 3 h (3 p.m.) before the time of sacrifice. No significant change is observed in type-3 SR index in animals subjected to any of the above treatments. The results indicate that exogenous melatonin may act directly on pinealocytes of the Chinese hamster to cause an increase in size and/or number of the type-1 and type-2 SR. Type 3-SR may have a role different from that of type-1 and type-2 SR; type-1 and type-2 SR may be functionally related.
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  • 191
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    Cell & tissue research 233 (1983), S. 227-231 
    ISSN: 1432-0878
    Keywords: Muscle-tendon junction ; Ultrastructure ; Myofibrillar pattern ; M. flexor digitorum longus ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The muscle-tendon junctions of adult mice show a special arrangement of myofibrils. Essentially, the myofibrils are oriented in an anchor-like manner in the large finger-shaped processes of the muscle fiber, which contain “mitochondrial sacks” (Demmel et al. 1979) in a subsarcolemmal position. Furthermore, the single myofibril frequently branches out into smaller fibrils. It is suggested that due to the three-dimensional arrangement, these processes gain a high rigidity during contraction, thus maintaining their shape and preserving the “mitochondrial sacks”.
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  • 192
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    Cell & tissue research 233 (1983), S. 265-284 
    ISSN: 1432-0878
    Keywords: Spermiogenesis ; Rainbow trout ; Ultrastructure ; Spermatids ; Chromatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In an ultrastructural study on the spermiogenesis of the rainbow trout (Salmo gairdneri R.) four spermatogenetic stages were identified. In young round spermatids, the nuclear chromatin was first heterogeneous (euchromatin and heterochromatin). Subsequently, it became more homogeneous and started to condense in the form of coarse granules and fibers and then into fibrils associated in ribbon-like elements which eventually partly fused together. During early spermiogenesis, a juxtanuclear vacuole appeared in the area where the nuclear envelope was specialized due to condensation of material between the two envelopes and a slight accumulation of nuclear material. This area was finally located in the anterior part of spermatids and spermatozoa; it probably plays a role during fertilization. A flagellar rootlet appeared early in spermiogenesis; it may play a role in the attachment of the flagellum to the nucleus since it persisted until the centriolar complex was definitively fixed in the implantation fossa. The flagellum did not display a plasma membrane and was first located in the cytoplasm, but when it was later extruded from the cell, it acquired a membrane. The cytoplasm was rich in ribosomes (free or in small groups) but poor in membranous organelles. The few mitochondria polarized around the centriolar complex were finally organized into an annular mid-piece. The spermatids remained connected by intercellular bridges until the end of spermiogenesis. The complexity of trout spermiogenesis is intermediate between that in poecilids and that in carp and pike, which have very simple spermatozoa. The role of the material from the nucleus and the cytoplasm reaching the Sertoli cell in the control of spermatogenesis has been discussed.
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  • 193
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    Cell & tissue research 232 (1983), S. 445-455 
    ISSN: 1432-0878
    Keywords: Avian thymus ; Intrathymic erythropoiesis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Although previously described in other avian species, intrathymic erythropoiesis is a remarkable feature of the thymus of Sturnus unicolor. In discrete stages of the life cycle of this species, erythroblasts and mature erythrocytes occupy large areas of the thymic cortex and cortico-medullary border. Simultaneously, degenerated thymocytes and epithelial-reticular cells occur in the same areas. The relationship between intrathymic erythropoiesis, degeneration of cortical lymphocytes and epithelial-reticular cells, and macrophage activity is discussed and related to a possible functional role of sex hormones in this phenomenon.
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  • 194
    ISSN: 1432-0878
    Keywords: Fetal macrophages ; Subepidermal mesenchyme (dermal tissue) ; Rat fetus ; Ontogeny ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary After about 12 days of gestation, fetal macrophages begin to appear in the subepidermal mesenchyme of rat fetuses. The macrophages are ultrastructurally characterized by cytoplasmic vacuoles, abundant polyribosomes and long filopodia. Immunocytologically, they possess Fc and complement (C3) receptors on the cell surface and are capable of immune phagocytosis, Latex or carbon phagocytosis, and glass adherence. From 15 days of gestation, lysosomal granules and miropinocytic vesicles gradually develop, together with an enlargement of Golgi complexes, whereas the number of polysomes and the number and size of cytoplasmic vacuoles are gradually reduced when gestation ends. Finally, the macrophages become amoeboid. Non-specific esterase and endogenous peroxidase activities are always absent in these macrophages. In culture experiments with cell suspensions prepared from the mesenchyme, fetal macrophages show a similar maturation process. Autoradiography with 3H-thymidine demonstrates a high proliferative capacity of the macrophages, particularly during the fetal stage.
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  • 195
    ISSN: 1432-0878
    Keywords: Ecdysteroids ; Epidermis ; In vitro differentiation ; Tenebrio ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In order to study the pupal-adult metamorphosis of Tenebrio in vitro, pupal sternites of different ages were cultured in Landureau's medium and their development systematically observed by electron microscopy. In hormone-free medium, explants taken from young pupae do not secrete pupal postecdysial cuticle in vitro, and the epidermis spontaneously detaches from the pupal cuticle. On the contrary, explants taken from pharate adults continue to secrete adult preecdysial cuticle in vitro, and the epidermis never detaches from the cuticle. Ecdysterone in physiological concentrations (0.2 to 4 μg/ml) induces the secretion of a new cuticle in explants from young pupae but the epidermis remains undifferentiated. Ecdysone is necessary for the induction of some adult differentiation. Moreover, the quality of the cuticle secreted in vitro is increased by the addition of 2% foetal calf serum; the best results have thus far been obtained in a medium containing 0.2 μg/ml ecdysone, 1 μg/ml ecdysterone, and 2% foetal calf serum.
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  • 196
    ISSN: 1432-0878
    Keywords: Skin ; Operculum ; Fenestration ; Ultrastructure ; Anura ; Metamorphosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The process of histolysis and fenestration of the skin of the prospective opercular perforation region of Rana japonica after extirpation of the right forelimb was observed during metamorphosis by transmission and scanning electron microscopy. Epidermal cells of the belly of the tadpole, including the operculum, are extremely similar in their ultrastructure. Epidermal cells of the prospective opercular perforation region during metamorphosis become thin and vacuolated especially around the nucleus perhaps by autolysis, associated with lysosomal activity. The histolysis and formation of the perforation of the operculum occurs in the complete absence of forelimb. Macrophages containing phagosomes and lymphocytes or other blood cells are almost always found in the intercellular epidermis. Necrotic epidermal cells progressively separate by cleft formation and slough off without cornification.
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  • 197
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    Investigational new drugs 1 (1983), S. 219-224 
    ISSN: 1573-0646
    Keywords: methyl-GAG ; rabbits ; pharmacokinetics ; three compartmental model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using a paired ion exchange high pressure liquid Chromatographic assay, pharmacokinetic evaluation of methyl glyoxal bis guanylhydrazone (methyl-GAG) was performed in nine male New Zealand albino rabbits following administration of a single intravenous bolus dose of 50 mg/kg B.W (550 mg/m2 BSA). Blood samples were collected before and at intervals of 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after administration of the drug. The analysis of experimental data indicates a three compartment open model with first order elimination from the central compartment described by the equation C pt =A.e−αt +B.e−βt +C.e−γt , where A, B, C, are 107.985, 4.785, and 0.763 μg/ml, respectively, α, β,γ, are 5.466, 0.487, and 0.030 h−1, respectively, and $$T_{\frac{1}{2}\alpha ,\beta ,\gamma } $$ are 7.6, 85.3 min and 23.1 h, respectively. The mean volume of distribution in the central compartment V c was 0.44 liters (l)/kg, volume of distribution Vd area 30.326 l/kg, and the total body clearance 0.9097 l/kg/h. The existence of a long terminal plasma half life of methyl-GAG reported previously in human studies was also confirmed in experimental animals and may explain the cumulative toxicity of this drug.
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  • 198
    ISSN: 1432-0878
    Keywords: Marsupial ; Ultrastructure ; Corpus luteum ; Granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary During embryonic diapause in the red-necked wallaby, M. r. banksianus, both the corpus luteum and uterine blastocyst remain dormant, and are reactivated following removal of the suckling pouch young (RPY). The morphology of dormant and reactivated corpora lutea has been studied throughout the 26.5 days of delayed gestation. Corpora lutea at 0, 2 1/2, 4, 9, 14, 21 and 25 days after RPY were fixed by perfusion. From day 4 to day 14 after RPY there was a progressive increase in the amount of smooth endoplasmic reticulum and the numbers of mitochondria. However there was a decrease in mitochondrial size from 1–2 μm in diameter (0 days after RPY) to 0.5–1 μm (14 days after RPY). Densely-staining granules (approximately 0.2 μm in diameter) were first observed in the luteal cells at 4 days after RPY. The maximum density of granules was observed at 21 days after RPY. Shortly before birth (25 days after RPY) the number of secretory granules had significantly decreased and the features of cellular regression were evident. As with the eutherian mammals, the wallaby luteal cells have all the structural organelles associated with steroid hormone production. The numbers of densely-staining granules are greatest at 21 days after RPY and may reflect the luteal progesterone content since similar granules in the sheep and cow have been shown to be associated with elevated levels of progesterone.
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  • 199
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    Cell & tissue research 230 (1983), S. 205-218 
    ISSN: 1432-0878
    Keywords: Kidney ; Glomerulus ; Ultrastructure ; Teleosts ; Seawater adaptation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The epithelial ultrastructure of the glomerulus of fresh- and sea-water adapted rainbow trout, Salmo gairdneri was examined by scanning and transmission electron microscopy after in vivo-perfusion fixation. Adaptation to seawater for a period of up to 9 weeks was not associated with a change in glomerular size, although after one year in seawater both glomeruli and their capsules were significantly smaller than the glomeruli of freshwater adapted fish. In freshwater adapted trout the epithelial ultrastructure conformed to the general vertebrate pattern, with rounded podocytes, well-defined primary processes and interdigitating pedicels. Adaptation to seawater was associated with a marked increase in the frequency of cytoplasmic microprojections. In many glomeruli there was a flattening of the podocytes, broadening of the primary processes, and areas of closely-packed pedicels were common. These observations are discussed in the light of previous studies on the mammalian kidney and the changes of single nephron function known to be associated with adaptation of trout to increased environmental salinities.
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  • 200
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    Cell & tissue research 230 (1983), S. 587-603 
    ISSN: 1432-0878
    Keywords: Pituitary ; Tammar wallaby ; Marsupial ; Neonate ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The pars distalis of pouch-young wallabies (Macropus eugenii) aged 1 to 50 days was studied by means of light-microscopic immunohistochemistry and electron microscopy. In the pars distalis of these pouch-young presumptive somatotrops, which constituted up to 70% of the gland, and nongranulated cells were the most numerous cell types. Small numbers (together representing less than 30% of the pars distalis) of immunoreactive mammotrops, thyrotrops, gonadotrops and corticotrops were also found. The presumptive mammotrops, gonadotrops and thyrotrops increased in number and apparent activity between 1 and 50 days postpartum. Presumptive corticotrop cells in 25 to 30 day-old animals were relatively most numerous, and apparently more active than at any other stage of pouch life; these cells decreased in apparent activity and relative number in older animals. The changes in number and activity of cell types in the pars distalis correlated well with major developmental events such as the onset of adrenal activity, the rapid growth phase in the first 100 days postpartum, and the generally low thyroid activity in pouch-young of less than 50 days of age.
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