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  • 1975-1979  (5,441)
  • Cell & Developmental Biology  (2,718)
  • Physics  (2,541)
  • Nuclear reactions
  • pharmacokinetics
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 203-209 
    ISSN: 1432-1041
    Keywords: dantrolene sodium ; spasticity ; twitch tension ; dose response ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dantrolen sodium is a muscle relaxant, which is used in the treatment of spasticity. Although it is given chronically, little is known about its pharmacokinetic behaviour. The relationship between the effect of a single oral dose of dantrolene sodium and its plasma concentration in healthy volunteers was studied by measuring the effect on the twitch tension, and in spastic patients on the decrease in muscle hypertonia. On the twitch tension dantrolene gave a depression of 49.1±9.4% (±SD) within 1.15 and 3.45 h after ingestion of 100 mg. The mean maximal plasma concentration was 1.24±0.32 µg/ml (±SD). The effect and the plasma concentration were correlated. No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients, although definite activity in 6 out of 7 patients was observed after a single oral dose of 100 mg, and plasma concentration of dantrolene sodium greater than 0.3 µg/ml were consistently associated with better results than placebo treatment in 6 out of 7 patients.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 287-293 
    ISSN: 1432-1041
    Keywords: linear system theory ; perfusion model ; cardiac output ; pulmonary extraction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Assessment of pharmacokinetics in terms of circulatory drug transport is proposed using the methods of linear system theory. In this model-independent approach drug distribution and disposition are characterized by the total extraction ratio, the mean residence time in the body and the volume of distribution at steady state. In analyzing concentration(c)-time(t) data, the procedure requires calculation only of the areas under the c(t)-and c(t)×t-curves to estimate kinetic parameters, and for prediction of the steady state concentration following continuous infusion or multiple doses. Pulmonary clearance of drugs is included in the theory.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 275-280 
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; bromocriptine ; pharmacokinetics ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma kinetics of bromocriptine (BCT), a long-acting dopamine agonist, was studied in twelve patients with Parkinson's disease, using a newly developed gas chromatographic method of analysis. Each patient received BCT for at least three weeks in a constant but different dose regimen. Concomitant treatment with 1-DOPA was not allowed. During a 6-day hospitalization period, a blood sample was taken immediately before the afternoon dose at 14.00 h (Cmin) to determine the steady-state level. On the 6th day blood samples were collected every hour during two 8 h dose intervals. The results showed a significant correlation between the mean values of the AUC and the Cmin. First order elimination kinetics appeared to be followed by BCT, at least for the plasma concentrations commonly found. Considerable inter-individual variation was demonstrated both for the dose/plasma concentration ratio and for calculated plasma clearances. No serious side-effects were observed during the investigation.
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  • 4
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; food effect on bioavailability ; repeated administration ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on bioavailability of indobufen tablets was investigated in 6 healthy volunteers. Subsequently, the same subjects took 100 mg b.i.d. for 7 days. Plasma levels and urinary excretion of indobufen were determined by GLC. Platelet aggregation induced by several concentrations of adrenaline was determined turbidimetrically at various times after the first and last doses. The absorption of indobufen tablets was not substantially impaired by the presence of food in the GI tract, although peak plasma levels and AUCs were slightly reduced after food. Pharmacokinetic analysis of plasma and urinary levels of indobufen did not indicate any change in drug disposition after repeated dosing. Adrenaline-induced platelet aggregation was markedly inhibited for up to 12 h after the first dose and the intensity and duration of this effect did not change after repeated administration. A twice-daily dosing appears suitable for clinical trials.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 341-347 
    ISSN: 1432-1041
    Keywords: clofibrate ; chlorophenoxyisobutyric acid ; disposition ; hepatitis ; cirrhosis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of clofibrate over 96 hours was observed following single oral dose in six patients with acute viral hepatitis, six patients with liver cirrhosis, seven patients with renal insufficiency, and six control subjects. No parameter of the disposition of CPIB (active form of clofibrate) was significantly altered in acute hepatitis. In liver cirrhosis, the mean plasma half-life was unchanged compared to controls (20.9 vs. 17.5 h), but plasma clearance of the non-protein bound drug was reduced (115 vs. 243 ml×min−1), plasma protein binding was reduced (92.8 vs. 97.2 percent), and the apparent volume of distribution was increased (0.20 vs. 0.141×kg−1). In renal insufficiency plasma half-life was prolonged 2 to 6-fold, depending on the degree of renal impairment. Total plasma clearance (3.4 vs. 7.1 ml×min−1) and plasma clearance of the unbound drug (81 vs. 243 ml×min−1 were reduced in patients with renal failure, the clearance of the unbound drug being inversely correlated with the serum creatinine concentration. Renal failure was also associated with decreased protein binding and an increased volume of distribution of CPIB, and with reduced urinary excretion of CPIB and its glucuronide metabolite. The dose of clofibrate should be halved in patients with cirrhosis. In renal insufficiency, the dose should be adjusted according to the individual serum creatinine level: only 10 to 15% of the usual weekly dose should be given in complete renal failure.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 363-366 
    ISSN: 1432-1041
    Keywords: methotrexate ; protein binding ; ultrafiltration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37°C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16±0.05 (S D) binding sites with an intrinsic association constant of 71.15±35.98 (S D)×104 M−1: Class II had 2.01±0.93 (S D) binding sites and an affinity of 0.18±0.15×104 M−1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 µMol 1−1.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 243-249 
    ISSN: 1432-1041
    Keywords: timolol ; beta blockade ; pharmacokinetics ; pharmcodynamics ; acute administration ; chronic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects of various oral doses of timolol administered either acutely or after chronic medication for 7 days were studied in healthy volunteers. After acute administration of timolol maximum plasma concentrations were attained within 1–2 h and thereafter declined exponentially with time. The mean apparent half-life of elimination from plasma was 2.5 h and was independent of dose. Area under the plasma concentration-time curve (AUC) was proportional to the orally administered dose. Plasma concentrations, apparent elimination half-life and AUC were not altered after one week of chronic administration. The effect of timolol on heart rate and blood pressure response to three sequentially increasing ‘steady state’ work loads were studied. After acute administration of timolol maximum reduction of systolic blood pressure, resting heart rate, and the different parameters of the work-heart rate (or blood pressure) relationships were produced by 5 mg timolol. Increasing the dose prolonged the duration over which these variables were reduced. The relationship between timolol plasma concentration and inhibition of different parameters of the exercise response was hyperbolic with half maximum inhibition at concentrations of about 3–4 ng/ml of timolol and maximum inhibition above 30 ng/ml. Maximum drug effects and duration of action of timolol on the different variables were similar after acute and chronic administration.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 263-270 
    ISSN: 1432-1041
    Keywords: diazepam ; alcoholic beverages ; plasma level ; pharmacokinetics ; co-ordination skills ; red wine ; white wine ; whisky
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty paid healthy students ingested diazepam 10 mg 30 min after the administration of ethanol 0.8 g/kg. The alcoholic beverage used was varied in randomized double-blind experiments, which were repeated at one-month intervals. Psychomotor performance, plasma diazepam, and alcohol concentration in breath were measured 30, 60, 90 min and 2, 3, 4, 6 and 24 h after the ingestion of diazepam. Beer and white wine elevated the plasma level of diazepam and the effect lasted for up to 2 h. Whisky elevated the diazepam level for 90 min. Red wine did not affect it significantly. The alcohol-diazepam combination impaired tracking skills and oculomotor co-ordination and enhanced nystagmus, more than diazepam alone. Red wine produced a breath alcohol concentration higher than after white wine. More nystagmus was recorded after red wine and diazepam, although white wine led to a higher plasma diazepam concentration. It appears that simultaneous ingestion of alcohol and diazepam accelerates the absorption of diazepam. This pharmacokinetic alteration may not contribute much to the combined psychomotor effects of diazepam and alcohol, which were mainly due to pharmacodynamic interaction at receptor level.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 271-277 
    ISSN: 1432-1041
    Keywords: lithium ; litarex ; single dose ; multiple dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An analysis of the single and multiple dose pharmacokinetics of lithium in 7 healthy volunteers is presented. A solution of lithium chloride was administered in single dose experiments and the same solution and a sustained release preparation were employed in multiple dose experiments, which were carried out at steady state. A fixed dose of 24 mmol was used in the single dose experiments and in the subsequent multiple dose experiments in the same subjects the same dose was administered once daily for a week. Distinct two-compartment characteristics were found, with a mean disposition rate constant (β) of 0.035 h−1±0.010 SD, corresponding to a mean biological half-life of about 19.8 h. The mean half-time of the distributory α-phase was about 1.15 h. The absorption of lithium from an orally administered solution took place with a half-time of about 0.15 h in the single dose experiments. The apparent volume of distribution of the central compartment (Vc) was 0.307 1 kg−1±0.046 SD, less than half that of Vde at equilibrium. Vdβ (Vdarea) was 0.8291 kg−1±0.184 SD and mean total body clearance was 27.6 ml kg−1 h−1±4.7 SD.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 255-262 
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; fluorimetry ; high performance liquid chromatography ; linear kinetics ; saturation kinetics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In Study I 20 normal volunteers received a single oral dose of spironolactone 100 mg. In Study II a further 20 normal volunteers were given first spironolactone 100 mg b.i.d. and subsequently spironolactone 100 mg once a day for a further 4 days. In Study III 5 normal subjects were given a single dose of spironolactone 500 mg. The concentration of canrenone in serum was determined both by fluorimetry and HPLC for 0–48 h in Study I, 120–168 h in Study II and 0–36 h in Study III. The total AUCs after the single 100 mg dose did not differ from the AUCs within the dosing interval during steady state. The half-lives of the terminal log-linear phases were almost identical (14.99±0.80 h and 15.69±0,80 h) when determined by fluorimetry, and were sligthly, but significantly (p〈0.01), longer when determined by HPLC — 20.14±1.62 and 18.71±1.04. The mean ratio of the specific AUC determined by HPLC and the fluorimetrically determined AUC was 0.3 after the single 100 mg dose. It did not differ from the corresponding value during steady state (0.34). In contrast, the ratio after the single 500 mg dose was approximately 50% higher. Fluorimetrically determined AUCs after 100 and 500 mg doses did not show dose-proportionality in contrast to the HPLC-determined AUCs. It was concluded that Canrenone contributes much less to the conventional fluorimetric determination than was previously assumed. It may not provide more than 1/10 and 1/4 of the antimineralocorticoid activity of spironolactone after single dose and multiple doses, respectively. Whereas linear kinetics apply after single and multiple 100 mg doses of spironolactone, after 500 mg saturation kinetics must be assumed with respect to metabolism. Thus, in bioavailability studies high doses of spironolactone should be avoided. For such studies the fluorimetric assay seems to be the appropriate bioanalytical method in spite of its lower specificity.
    Type of Medium: Electronic Resource
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 187-192 
    ISSN: 1432-1041
    Keywords: quinidine ; plasma protein binding ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 153-157 
    ISSN: 1432-1041
    Keywords: cimetidine ; renal failure ; elimination half life ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curve after a single oral dose of cimetidine 200 mg was followed in 27 patients with varying degrees of chronic renal failure (creatinine clearance 1–52 ml/min) and in 46 patients with normal serum creatinine. Compared to the latter patients, the plasma concentration was higher and the elimination rate was slower in all uraemic subjects, including a group with moderate renal impairment. The preliminary recommendations of dosage for patients with a creatinine clearance below 5 ml/min, and for patients on regular haemodialysis, is cimetidine 200 mg every 12 h, 5–15 ml/min 200 mg every 12 to 8 h, 15–30 ml/min 200 mg every 8 h and 30–52 ml/min 200 mg every 6 h.
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  • 13
    ISSN: 1432-1041
    Keywords: nitrazepam ; epilepsy ; age ; disease ; plasma concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nitrazepam were measured by gas-liquid chromatography in: young healthy volunteers, in geriatric and psychiatric patients and in epileptic children. The disposition of nitrazepam was described in terms of a two-compartment open model. After a single oral dose of nitrazepam 5 mg the most prominent differences between the experimental groups were in the β-phase half-life-mean 29 h in the young volunteers and 40 h in geriatric patients, and in the apparent volume of distribution during the β-phase of 2.4 vs 4.8 l/kg. Total plasma clearance and the average steady state concentration in both groups were equal. The plasma level rose at a rate proportional to the β-phase half-life, and so, they were achieved more rapidly in the young than in the old subjects (3.5 vs 7.5 d). No change in steady-state level or in the half-life of nitrazepam were found during long term treatment, which indicates lack of enzyme induction or inhibition. In 95% of the epileptic children with a good to fair clinical response, the plasma concentration of nitrazepam was 40–180 ng/ml (mean 114 ng/ml). As all of the patients were on combined antiepileptic therapy, no attempt was made to correlate plasma level with therapeutic response.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 175-180 
    ISSN: 1432-1041
    Keywords: clorazepate ; nordiazepam ; pregnancy ; pharmacokinetics ; intramuscular injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77h in pregnant women and 0.56h in non-pregnant women; elimination half life 1.3h in pregnant women and 2.0h in non-pregnant women; volume of distribution: 0.43 l · kg−1 in the pregnant women and 0.33 l · kg−1 in non-pregnant women. Nordiazepam reached its peak concentration within 12h after dosing; its mean half life of elimination was 180h in pregnant women and 60h in non-pregnant women. Within 24h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 257-261 
    ISSN: 1432-1041
    Keywords: cimetidine ; H2-receptor antagonist ; aging ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r=0.81; P〈0.001). The peak concentrations of cimetidine were significantly inversely related to body weight (r=−0.71; P〈0.001). The age-related increase in bioavailability of oral cimetidine, as measured by AUC, was probably due to decreased total clearance of the drug, which resulted from the opposed changes (by themselves not significant) of distribution volume towards a decrease and of half-life towards an increase with age. Reduction in the standard oral dose of cimetidine by one third to one half should be feasible in the elderly without loss of efficacy, and it may be advisable in order to obviate extreme individual responses that may occur in this population.
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  • 16
    ISSN: 1432-1041
    Keywords: chlorthalidone ; pharmacokinetics ; oral and i.v. doses ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven normal human volunteers each received a constant-rate infusion of chlorthalidone for 2 h, and the same (commonly 50 mg) single oral dose on separate occasions. The concentration of unchanged chlorthalidone was analyzed over a 100 to 220 h period in plasma, red blood cells, urine and faeces after both dosage forms. A three compartment model was required to describe the intravenous plasma concentrations in five of the subjects. A two compartment model sufficed to account for the decay of the oral plasma concentrations in all seven subjects. The mean plasma t1/2 after i.v. dosing was 36.5 h (±10.5 SD), and the mean plasma t1/2 after oral doses was 44.1 h (±9.6 SD). The mean red blood cell concentration t1/2 after i.v. doses was 46.4 h (±9.9 SD), and the mean red blood cell t1/2 after the oral doses was 52.7 h (±9.0 SD). The shorter i.v. half-live was not equally manifest in all subjects, being mainly apparent in three of them. In all cases the urinary excretion rate plots were parallel to the plasma concentration curves. As the faster decay after i.v. administration was not accompanied by increased renal clearance, the difference must have been due to non-renal mechanism. The mean total of 65.4 (±8.6 SD) % of the intravenous dose was excreted in urine over infinite time, whereas the mean total excretion after the oral dose was 43.8 (±8.5 SD) %. Faecal excretion ranged from 1.3–8.5% of dose in the i.v. study to 17.5–31.2% of dose in the oral study. The sum of the amounts present in urine plus faeces pointed strongly to an important metabolic route of elimination of chlorthalidone. Bioavailability estimates (F) from three sets of data were — a mean F of 0.61 from plasma concentrations, 0.67 from urinary excretion measurements and 0.72 from the erythrocyte concentrations. Simulations with a non-linear model indicated lesser validity of the estimate from erythrocyte concentrations. It was concluded that the average of plasma and urine data, F=0.64, yielded the best estimate of the oral availability of chlorthalidone 50 mg in man.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 121-125 
    ISSN: 1432-1041
    Keywords: guanethidine ; chronic therapy ; urinary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma level and urinary excretion rate of guanethidine have been measured in 30 patients during oral maintenance therapy, and in 5 patients following discontinuation of therapy. A significant correlation was found between the daily average urinary excretion and the maintenance dose, although wide interindividual variation was noted among patients maintained on the same dose. A statistically significant correlation was also observed between the area under the plasma level curve during the dose interval and the oral maintenance dose. After discontinuation of chronic therapy, the half-life of 1.5 days of the initial phase of elimination was essentially in agreement with the half-life of almost 2 days determined in acute studies. In addition, a second phase of elimination with a half-life of 4 to 8 days was observed.
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  • 18
    ISSN: 1432-1041
    Keywords: clorazepate ; nordiazepam ; pregnancy ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clorazepate 20mg was given i. m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. “Total nordiazepam”, i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 31-38 
    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
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  • 20
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 433-441 
    ISSN: 1432-1041
    Keywords: cyclobarbital ; barbiturates ; pharmacokinetics ; drug interaction ; volunteers ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disappearance of cyclobarbital from plasma has been followed in healthy volunteers and in neurological and psychiatric patients after oral administration of one tablet of Phanodorm®, containing cyclobarbital calcium 200 mg. Plasma levels were measured by a thin-layer chromatographic method with in situ densitometry. The average t1/2 in healthy female and male volunteers was 13.3 h, and with the assumption of complete availability a mean distribution coefficient of 0.69 l/kg−1 and a clearance of 40.4 ml/min−1 were calculated. Repeated experiments in seven volunteers revealed good reproducibility of all values. When the healthy volunteers were combined with a group of untreated epileptics, a dependence of t1/2 and of the apparent volume of distribution on age was found, while clearance did not change with increasing age (range 17–54 years). Long half-lives caused by low clearance values were observed in several individuals with moderate obesity. No consistent change in cyclobarbital kinetics followed acute exposure of volunteers to alcohol or on treatment of neurological patients with carbamazepine. Patients under treatment with perazine exhibited more or less normal kinetic values. In terms of drug interaction, cyclobarbital differs from phenazone in several respects, and so it may prove a useful additional substance for measurement of the rate of drug oxidation in humans.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 1-6 
    ISSN: 1432-1041
    Keywords: lorcainide ; ventricular premature beats ; plasma levels ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma level and antiarrhythmic effect of lorcainide (R 15889) have been investigated in 15 patients with ventricular premature beats (VPB). Therapy was initiated with an intravenous dose of 1.9 mg/kg given over 10 min, followed by a constant infusion of 0.18 mg/kg/h for 24 h. In 8 patients the corresponding doses were increased to 2 mg/kg and 0.27 mg/kg/h. After the intravenous doses patients were treated orally with 100 mg tid for 6–7 days. The two dosage regimens were selected so as to achieve theoretical steady-state plasma levels (css) of 200 and 300 ng/ml, respectively. The combined intravenous treatment approached (181 ± 6.8 ng/ml and 273±28.5 ng/ml, respectively) the desired css within 2 to 4 h. During the oral administration, the minimal plasma concentrations following the lower intravenous dose (184±18 ng/ml) were significantly (p=0.0001) lower than after the higher intravenous dose (264±20.5 ng/ml). The dealkylated metabolite of lorcainide was not detectable after the intravenous doses, but it accumulated during oral treatment, when its concentration exceeded that of the parent compound. In 5 of the 7 patients receiving the lower dose VPB were effectively reduced. However, in only 4 of the 8 patients on the higher dosage schedule could a significant antiarrhythmic effect be demonstrated. In addition, side effects were observed in 6 of the subjects.
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  • 23
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    European journal of clinical pharmacology 16 (1979), S. 23-29 
    ISSN: 1432-1041
    Keywords: valproate ; epilepsy ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In four refractory epileptic patients, peak plasma levels of sodium valproate occurred within 1.5 to 3 h after a single oral dose of valproate and the decline in plasma levels followed a monoexponential course with a t1/2 of 11.4 ± 0.1 h. The mean value for apparent volume of distribution was 0.176 ± 0.013 l/kg and for total plasma clearance 0.0106 ± 0.0009 l/h/kg. Steady state plasma levels were predicted using the method of superposition utilizing pharmacokinetic parameters determined following a single dose of valproate and were 78–123% of the predicted values for two patients receiving valproate alone, and 37–64% of the predicted values for the two patients receiving carbamazepine in addition to valproate. In a further group of 20 patients the mean daily doses of valproate for 8 patients receiving valproate alone (25.4 ± 4.9 mg/kg) was significantly less than those for the 12 patients receiving concomitant anticonvulsant therapy (41.6 ± 12.3 mg/kg) (p〈0.005). In addition, the steady state predose plasma levels of valproate were significantly higher in the valproate alone patients (90.3 ± 8.7 µg/ml) compared to the patients receiving additional anticonvulsants (75.3 ± 13.8 µg/ml) (p〈0.01). The higher dose requirements of valproate and lower predose and steady state plasma levels for those patients on multiple anticonvulsants indicate an interaction between valproate and other anticonvulsants.
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  • 24
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    European journal of clinical pharmacology 16 (1979), S. 45-48 
    ISSN: 1432-1041
    Keywords: quinidine ; slow release formulation ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median value 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.
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  • 25
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    European journal of clinical pharmacology 16 (1979), S. 49-52 
    ISSN: 1432-1041
    Keywords: cephacetrile ; haemodialysis ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cephacetrile were studied after its administration as a single i.v. bolus injection of 15 mg/kg body weight to 11 patients with terminal renal inpairment undergoing haemodialysis for 6 h. A two-compartment kinetic model was used to describe the biphasic decrease in plasma concentration. The quantities of antibiotic in the central and peripheral compartments, and the amounts eliminated, were calculated for different times. During haemodialysis sessions, the average pharmacokinetic parameters of cephacetrile determined at the dialyser input were: α=5.03 h−1,β=0.458 h−1, K12=2.337 h−1, K21=1.996 h−1 K13=1.154 h−1, Vc=5.508 l, Vp=6.448 l, Vdss=11.956 l. As a function of the pharmacokinetic parameters of cephacetrile, a regimen of multiple doses was established for patients with terminal renal impairment, which will guarantee safe and effective concentrations of the antibiotic.
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  • 26
    ISSN: 1432-1041
    Keywords: methadone ; mass fragmentography ; pulse labeling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d3) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d0) was substituted by one dose of methadone-d3 and plasma levels of methadone-d0 and methadone-d3 were followed for 48 h using a precise (SD±5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (t1/2) for both methadone-d0 and metadone-d3 were calculated from samples obtained 8–24 h following the dose of methadone-d3. The t1/2 of oral methadone-d3 was shorter (22±2 h) than that of methadone-d0 (52±20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body.
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  • 27
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    European journal of clinical pharmacology 16 (1979), S. 177-181 
    ISSN: 1432-1041
    Keywords: prazosin ; alpha receptor blockade ; blood pressure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects of prazosin have been studied after intravenous and oral dosing (1 mg) to 6 normal male volunteers. The mean terminal (β) half-life was 2.9 h after intravenous and oral routes. Oral bioavailability was 56.9%. The effects of prazosin on blood pressure were more pronounced after intravenous than oral administration, and the hypotensive effect greater on erect blood pressure. There was a significant correlation (P〈0.02) between the fall in blood pressure and the plasma drug concentration after intravenous prazosin.
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  • 28
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    European journal of clinical pharmacology 16 (1979), S. 189-194 
    ISSN: 1432-1041
    Keywords: sparteine ; pharmacogenetic defect ; defective metabolism ; pharmacokinetics ; renal excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sparteine is metabolized by N1-oxidation, which in some subjects is defective. The defect has a pronounced effect on the kinetics of the drug. In non-metabolisers elimination of sparteine proceeds entirely via renal excretion by a capacity-limited process, 99,9% of the dose being excreted as unchanged drug. In metabolisers the drug is mainly eliminated by metabolic degradation. Pronounced differences in β-phase half-life and total plasma clearance were observed between metabolisers (156 min; 535 ml · min−1) and nonmetabolisers (409 min; 180 ml · min−1).
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  • 29
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    European journal of clinical pharmacology 16 (1979), S. 195-202 
    ISSN: 1432-1041
    Keywords: metformin ; biguanides ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of14C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9±1.61 ( $$\bar X$$ ±SE), from which its elimination could be described using three-compartment open model. The elimination half-life from plasma was 1.7±0.1 h. Urinary excretion data revealed a quantitatively minor terminal elimination phase with a half-life of 8.9±0.7 h. After the intravenous dose, metformin was completely excreted unchanged in urine with a renal clearance of 454±47 ml/min. Metformin was not bound to plasma proteins. The concentration of metformin in saliva was considerably lower than in plasma and declined more slowly. The bioavailability of metformin tablets averaged 50–60%. The rate of absorption was slower than that of elimination, which resulted in a plasma concentration profile of “flip-flop” type for oral metformin.
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  • 30
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    European journal of clinical pharmacology 16 (1979), S. 327-330 
    ISSN: 1432-1041
    Keywords: atenolol ; food intake ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.
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  • 31
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    European journal of clinical pharmacology 16 (1979), S. 331-334 
    ISSN: 1432-1041
    Keywords: netilmicin ; radioenzymatic assay ; drug accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharmacokinetic parameters. Following the rapid initial distribution, biphasic elimination with half lives of 1.99 h (t1/2β) and 36.89 h (t1/2γ) was demonstrated. Measurable amounts of NM were excreted in the urine for up to 72 h. The volume of distribution at steady-state (Vdss) of 0.68 l/kg was 3 to 4 times larger than previously reported for this antibiotic. NM plasma clearance was 91 ml/min and the renal clearance was 67 ml/min. The data indicate that on repetitive dosing the amount of drug in the body would be considerably underestimated if the prolonged terminal elimination phase were not taken into account. During prolonged treatment, accumulation of NM in renal and other tissues is likely to occur, as has been described for other aminoglycosides. The possible consequences of this pharmacokinetic behaviour are discussed.
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  • 32
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    European journal of clinical pharmacology 16 (1979), S. 335-340 
    ISSN: 1432-1041
    Keywords: cimetidine ; enterohepatic circulation ; irregular absorption ; bioavailability ; pharmacokinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
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  • 33
    ISSN: 1432-1041
    Keywords: prenalterol ; metoprolol ; haemodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of the selectiveβ 1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selectiveβ 1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/1) prenalterol had to be administered in doses that were twelve times higher than before theβ-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.
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  • 34
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    European journal of clinical pharmacology 15 (1979), S. 269-274 
    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.
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  • 35
    ISSN: 1432-1041
    Keywords: myasthenia gravis ; neostigmine ; gas chromatography-mass spectrometry ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To permit rational evaluation of the empirical pharmacotherapy of myasthenia with cholinesterase inhibitors, a sensitive and selective method for the determination of neostigmine has been developed. Analysis is based on ion-pair extraction of neostigmine into methylene chloride and determination by gas chromatography-mass spectrometry (chemical ionization). As neostigmine was found to be metabolized in plasma in vitro, deuterated (d6) neostigmine was immediately added to the plasma sample as the internal standard. The limit of quantitation of the method was about 1 ng/ml (∼ 3nmol/l). The kinetics following i. v. administration were studied in four patients, who received neostigmine 2.5–3.0 mg iv to antagonize pancurone administered during anaesthesia. Elimination was rapid with a half-life t1/2 (β-slope) of 0.89±0.05 h (mean ± SE). The volume of distribution was 1.08±0.11 l/kg and plasma clearance was 0.84±0.04 l/kg/h. In three fasting myasthenic patients plasma concentrations of neostigmine were followed for 5 h after a single oral dose of 30 mg. Considerable interindividual differences in absorption were expressed in the peak concentrations, which occurred 1–2 h following drug ingestion. The bioavailability of neostigmine was estimated to be 1–2% of the ingested dose. Neostigmine concentration in plasma was found to differ considerably (up to forty-fold) between myasthenic patients on their ordinary dose-schedules of cholinesterase inhibitors.
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  • 36
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    European journal of clinical pharmacology 16 (1979), S. 101-105 
    ISSN: 1432-1041
    Keywords: dihydroquinidine ; congestive heart failure ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of dihydroquinidine were studied in 8 patients with congestive heart failure following a 22 min intravenous infusion of a quinidine preparation that contained 5.9% dihydroquinidine as an impurity. Using a thin layer chromatography-fluorometric assay procedure for dihydroquinidine, the post-infusion plasma dihydroquinidine concentrations declined biexponentially. The half-life of the fast and slow dispositional processes was 4.42±1.81 min and 6.52±2.40 h, respectively. The central compartment volume for dihydroquinidine in these patients was 0.44±0.11 l/kg with an overall apparent volume of distribution of 1.14±0.38 l/kg. The computed values of total body plasma clearance of dihydroquinidine ranged from 1.29 to 2.69 ml/min/kg with a mean value of 1.94±0.60 ml/min/kg. In these patients, approximately 16% of the administered dihydroquinidine dose was excreted intact into the urine in 48 h. The estimated value of renal clearance was 0.314±0.129 ml/min/kg. When compared to control cardiac patients, the data showed that the apparent volume of distribution for dihydroquinidine is smaller in patients with congestive heart failure and as a result of this diminished volume, the clearance rate of dihydroquinidine was slower. The net effect of these differences was the production of higher plasma concentrations of dihydroquinidine in the heart failure group.
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  • 37
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    European journal of clinical pharmacology 16 (1979), S. 119-124 
    ISSN: 1432-1041
    Keywords: cefoxitin ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin have been determined after a single i.v. injection of 15 mg/kg body weight in 10 patients with normal renal function and 20 patients with varying degrees of renal impairment. The kinetics of the antibiotic followed an open two-compartment model. In patients with normal renal function the following pharmacokinetic parameters were found: $$\begin{gathered} \begin{array}{*{20}c} {\alpha = 8.66 h^{ - 1} } & {\beta = 1.21 h^{ - 1} } & {K_{12} = 3.47 h^{ - 1} } \\ \end{array} \hfill \\ \begin{array}{*{20}c} {K_{21} = 3.17 h^{ - 1} } & {K_{13} = 3.15 h^{ - 1} } & {V_c = 4.24 l.} \\ \end{array} \hfill \\ \begin{array}{*{20}c} {V_p = 4.87 l.} & { Vd_{ss} = 9.11 l.} \\ \end{array} \hfill \\ \end{gathered}$$ In the patients with renal impairment there was a significant decrease in $$\mathop \alpha \limits_, \mathop \beta \limits_, $$ K12, K21 and K13, and an increase in the apparent volume of distribution. The degree of plasma protein binding in patients with normal renal function was 73.6% and this was diminished in patients with renal impairment. A linear relationship between K13 of cefoxitin and creatinine clearance was demonstrated. The dosage regimen for patients with renal impairment should be adjusted by modifying the dosage interval whilst maintaining the amount administered.
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  • 38
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    European journal of clinical pharmacology 16 (1979), S. 133-139 
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six children, aged 2 months – 4 years, received theophylline 5–6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t1/2 β) was 3.75 h, i. e., shorter than in adults, but there was a considerable interindividual variation (1.8–7.0 h, in one patient 13.3 h). Thirteen children (2 months – 4 years) received theophylline suppositories in a dose of 3.8–5.0 mg/kg, and ten (6 months – 4 years) in a dose of 8.4–14.5 mg/kg. Absorption was slow (mean half-time 43 min), incomplete and variable (biological availability 8–100%, mean 80%). Only four of the patients given the higher dose and none given the lower dose reached a therapeutic serum concentration (10–20 µg/ml). Nine children (6 months – 4 years) received rectal enemas of theophylline 4.1–9.2 mg/kg. Absorbtion was rapid (mean half-time 5.5 min) and biological availability averaged 100%. Six patients reached a serum concentration within the therapeutic range. Using the mean values of the calculated pharmacokinetic parameters, rectal enemas providing a dose of theophylline of 6–8 mg/kg t. i. d. were computed to give serum concentrations between 8–20 µg/ml, without producing too high a level during the absorption phase.
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  • 39
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    European journal of clinical pharmacology 16 (1979), S. 279-285 
    ISSN: 1432-1041
    Keywords: salicylate ; synovitis ; osteoarthritis ; arthritis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Samples of blood and joint fluid from 30 patients who had taken buffered acetylsalicylic acid were examined for concentrations of total salicylates (TSA), acetylsalicylate (ASA) and salicylate (SA). The data were arranged in groups according to diagnosis of the joint disease. Analysis of the data did not show significant difference in the kinetics of TSA into blood. In groups the time to first appearance of 0.3 mg/l averaged 6.3 min for TSA; these values averaged 7.7 min for ASA and 10.9 min for SA. Close to maximum concentrations in blood averaged 18.9 mg/l for TSA, 3.3 mg/l for ASA, and 23.3 mg/l for SA. The time for first appearance of 0.3 mg/l of total salicylates in joint fluid ranged from 10 to 34 min with an average of 18.1 min; the values of ASA averaged 19.4 min and those of SA 21.9 min. The maximum concentration in joint fluid averaged 15.7 mg/l for TSA, 2.5 mg/l for ASA, and 14.5 mg/l for SA. Transport of salicylates from blood to joint fluid showed a pattern consistent with the type of joint disease. Support was found for the hypothesis that diffusion was the major factor in the movement of salicylates from blood to joint fluid.
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  • 40
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    European journal of clinical pharmacology 16 (1979), S. 411-416 
    ISSN: 1432-1041
    Keywords: doxapram ; intravenous infusion regimen ; pharmacokinetics ; data-point weighting ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous doxapram in healthy individuals is consistent with a three-compartment open model. Doxapram was administered by bolus injection (1.5 mg · kg−1) and by intravenous infusion (6.5 mg · kg−1 for 2 h) to 5 subjects on separate occasions. There was no significant difference in mean terminal plasma half-lives (355 and 448 min) or in mean total body clearances (5.9 and 5.6 ml · min−1 · kg−1) following i. v. bolus injection or infusion respectively. In 3 subjects plasma doxapram concentrations during and after i. v. infusion agreed with those predicted from pharmacokinetic values obtained from the bolus injection study. Since mean steady-state concentrations (9.9 µg · ml−1) would be reached only after an extended interval (mean 15.2 h), a variable-rate infusion regimen was calculated to produce and maintain a concentration of 2 µg · ml−1 from 15–25 min onwards. A regimen in which the infusion rate is reduced step-wise is recommended to achieve early near-constant plasma doxapram concentrations.
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  • 41
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    European journal of clinical pharmacology 15 (1979), S. 105-108 
    ISSN: 1432-1041
    Keywords: muzolimine ; cardiac failure ; pharmacokinetics ; high ceiling diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new “high ceiling” diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I–IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1–3 h after administration and declined according to a two-compartment model. The α-phase (distribution phase) lasted until 12–16 h after administration and the mean t1/2α was 3.6 h (range 2.3–4.7) in patients, and 2.6 h (range 2.3–2.9) in healthy subjects. The mean t1/2β was 13.5 h (range 7.4–22.4) in the patients and 14.0 h (range 12.4–14.6) in healthy subjects. T1/2β was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7–15.3 ml · min−1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.
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  • 42
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    European journal of clinical pharmacology 15 (1979), S. 115-120 
    ISSN: 1432-1041
    Keywords: digoxin ; right heart failure ; absorption ; absolute bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of digoxin has been investigated in 8 patients before and after successful treatment of severe right heart failure.3H-digoxin 0.1 mg as a solution, and un-labelled digoxin 0.25 mg as a tablet, were given to fasted patients. Blood samples were taken at various time intervals up to 120 hours and urine was collected over the same period. The concentrations of labelled digoxin in plasma and urine were measured in a liquid scintillation counter, unlabelled digoxin was estimated by radioimmunoassay, and various pharmacokinetic parameters were calculated. There was no significant difference in the plasma concentration curves in severe right heart failure and after its successful treatment, nor did any of the calculated pharmacokinetic parameters change significantly. Therefore, inhibition of the absorption of digoxin appears unlikely. In an additional study to estimate absolute bioavailability two different groups of patients in severe right heart failure were given3H-digoxin 0.1 mg or unlabelled digoxin 0.25 mg i. v. and the pharmacokinetic parameters were compared with those from the previous study. The bioavailability of the3H-digoxin solution and of the digoxin tablet were in the same range as values previously published for healthy volunteers, and patients both with and without cardiac failure.
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  • 43
    ISSN: 1432-1041
    Keywords: metoprolol ; tachycardia ; healthy subjects ; conventional tablets ; slow release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and associated reduction in exercise-induced tachycardia have been examined following the administration of single doses of metoprolol in conventional and slow-release tablets at different times to six healthy male subjects. The study was carried out in two parts. Initially, the tablets were given at 9 a. m. and the subjects were studied up to 14 h and then at 24 h. Subsequently, the same doses were given at 9 p. m. and the subjects were studied 12–24 h after drug administration (i. e. 9 a. m.–9 p. m. the next day). After giving the slow-release tablets the peak plasma levels were significantly lower but the drug persisted in the plasma at higher levels than after the conventional tablet. However, the beta-blocking effect was comparable from the two dosages. The results obtained for the period 12–24 h after the evening dose differed from the corresponding values after morning administration in that the plasma levels were higher and the betablocking effects more marked. Furthermore, the half-life values calculated from these data were significantly longer.
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  • 44
    ISSN: 1432-1041
    Keywords: triamterene ; pharmacokinetics ; diuretic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urinary levels of triamterene and two metabolites were measured using a specific method of analysis. Urinary excretion was completed after 48 h, which permitted a rough estimate of its half-life as longer than two hours. The areas under the curve were 672.5±160.3 and 1.311.3±399.1 µg/ml × h after the triameterene 150 mg and 300 mg p.o., respectively and correspondingly 4.2±1.4% and 3.7±0.6% of the dose were excreted as unchanged drug. The principal metabolite of triamterene found was the sulfate conjugate. The area under the curve of this metabolite amounted to 6.672±2.120 and 11.941±5.005 µg/ml × h after the of 150 mg and 300 mg triamterene doses, respectively. The urinary excretion of the metabolite varied between 25.0±4.0% and 17.5±3.5% of the dose after either dose. In healthy subjects an effect on sodium excretion was observed after a dose of 150 mg, whereas the potassium-retaining effect was observed only after the dose of 300 mg.
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  • 45
    ISSN: 1573-8744
    Keywords: lorazepam ; benzodiazepines ; pharmacokinetics ; drug accumulation ; antipyrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Six healthy volunteers participated in single- and multiple-dose pharmacokinetic studies of oral lorazepam. Following single 4-mg oral doses, peak plasma lorazepam concentrations ranging from 40 to 70 ng/ml were reached within 3 hr of the dose. Values of absorption half-life averaged 25min (range 10.3–42.7min), and elimination half-life (t 1/2β ) averaged 14.2 hr (range 8.4–23.9 hr). During 15 consecutive days of 3 mg per day administered in divided doses, accumulation to the steady-state condition was complete within several days of the initiation of therapy. Values of accumulation half-life (mean 21.1 hr) were slightly longer than t 1/2β , and the two were not well correlated. Observed accumulation ratios (mean 1.88) were very close to those predicted from the single-dose study (mean 1.77), but the correlation between the two (r=0.51) was not significant in the small sample size. “Washout” half-life values (mean 14.9 hr) were highly correlated with t 1/2β (r=0.92). Clearance of a single intravenous dose of antipyrine determined prior to the multiple- dose lorazepam study (mean 0.86 ml/min/kg) was essentially identical to that determined after the study (mean 0.87 ml/min/kg). Overall, the rate and extent of lorazepam accumulation during multiple dosage were reasonably well predicted by the single-dose kinetic study. However, accurate prediction for any specific individual was not always achieved. Stimulation or inhibition by lorazepam of its own clearance probably does not explain imprecise prediction, since single-dose t 1/2β .
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  • 46
    ISSN: 1573-8744
    Keywords: procainamide ; pharmacokinetics ; constant-rate infusion ; acetylator phenotype ; pharmacogenetics ; renal impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClTs of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.
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  • 47
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 249-264 
    ISSN: 1573-8744
    Keywords: dexamethasone ; pharmacokinetics ; renal excretion ; high-performance liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid Chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest poly exponential equation that is consistent with the data. The terminal phase half-lifet 1/2β was significantly greater (p〈0.05) in males (mean 201.5 min) than in females (mean 142.3 min). The prolongedt 1/2β in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 247.5ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation betweent 1/2β and $$V_{d_{ss} } $$ among the 12 adults (r=0.92, p〈0.001). There were also significant correlations between $$V_{d_{ss} } $$ and body weight (r=0.67, p〈0.05) andt 1/2β (r=0.80, p〈0.01).The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t 1/2β. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms.
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  • 48
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 383-396 
    ISSN: 1573-8744
    Keywords: chlorpheniramine ; pharmacokinetics ; oral absorption ; first-pass effect ; saturation kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of chlorpheniramine has been studied in six dogs by following the time course of plasma concentration of the drug after intravenous and oral administration of its maleate salt in solution form. After intravenous dosing the decline in chlorpheniramine plasma concentration was typically biexponential. The drug distributed rapidly and extensively to the extravascular tissues. The mean distribution phase halflife was 12.5 min, and the mean apparent volume of distribution, Vdβ, was 525% ofthe body weight in four dogs with normal hematocrits. The mean half-life of elimination was 1.7hr. The percent absolute availability following oral administration of the drug in the aqueous solution form was found to be dose dependent. At 100-mg dose, in six dogs, an average of 36% of the orally administered dose was found to be systemically available. At 50-mg dose, in one of the four dogs studied, no measurable plasma levels of chlorpheniramine were obtained, and the average bioavailability was only 9.4%. The average availability in four dogs at 200-mg dose was 39.4%. Even at 200-mg oral dose, the dogs did not show any signs of sedation and remained alert all through the experiment. Saturable first-pass gut and/or hepatic elimination has been postulated. The possible implications of these findings on the therapeutic effectiveness of the usual dosing regimen of chlorpheniramine in dogs are discussed.
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  • 49
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 481-494 
    ISSN: 1573-8744
    Keywords: clonidine ; pharmacokinetics ; blood and brain levels ; liver clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To investigate the pharmacokinetic behavior of clonidine, rats were given clonidine intravenously at 125, 250, and 500μg/kg and blood clonidine concentrations were followed for 6 hr. The disposition of clonidine in two brain regions was studied in rats after an i. v. dose of 500 μg/kg. The liver clearance in rats was investigated by liver perfusion techniques. The results obtained indicate that the disposition characteristics of clonidine can be described by a two-compartment open model in both rats and cats. The penetration of clonidine into tissues is rapid, and brain levels in rats were about 1.7 times higher than blood levels. Brain tissues were found to be an indistinguisible part of the central (blood) compartment. Dose-dependent pharmacokinetic behavior was found for clonidine in rats at the doses used. This was demonstrated by a decrease of both the rate constant of distribution to the peripheral compartment and the overall elimination rate constant from the body, with increase in dose. As a consequence, the volume of distribution and the clearance both decreased with increasing dose. Possible explanations for the dose-dependent behavior of clonidine are discussed.
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  • 50
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 527-536 
    ISSN: 1573-8744
    Keywords: instantaneous distribution ; pharmacokinetics ; pulmonary first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The classical concept of assuming that an i.v. dose instantaneously distributes into the central or plasma compartment is reviewed, as is the potential for pulmonary first-pass effect. Based on available literature, the concept is shown to lead to serious errors in estimating pharmacokinetic parameters, particularly for drugs with high clearance.
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  • 51
    ISSN: 1573-8744
    Keywords: clonidine ; pharmacokinetics ; analgesia ; blood pressure effects ; smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The time course of an observed pharmacological effect is affected not only by the kinetics of the drug levels at the site of action but also by parameters such as the slope and maximum effect of the functional relationship between drug level and response. Using clonidine as a test drug, it was found that the kinetics of its effects on blood pressure and pain responses cannot be described by the time course of clonidine levels in the blood, brain, or the hypothetical tissue compartment of the two-compartment characteristics of this drug. However, the results can be explained assuming that the observed pharmacological effects of a drug are composed of the sum of responses from at least two receptor sites with different slopes and maximal effects. The effect of intravenously administered clonidine on blood pressure in the rat was found to be related to the blood concentrations at least at two receptor sites with opposite effects, one leading to a hypertensive and the other to a hypotensive response. Predictions indicate that a maximum decrease of arterial blood pressure is obtained when the steady-state blood concentration of clonidine is about 1 ng/ml and that no effect is seen at 10 ng/ml. Higher levels will produce an increase of the pressure. The kinetics of the analgesic effect of clonidine in the rat could best be related to the brain levels if the observed effect was considered to be derived from the sum of activity at two receptor sites each producing analgesia. The kinetics of the effects of clonidine on the nictitating membrane of the cat was found to be determined by the kinetics of the drug in the peripheral compartment of the two-compartment open model. Consideration of multiple receptor responses is suggested for future studies on the relationship between the kinetics of drug levels and pharmacological responses.
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  • 52
    ISSN: 1573-8744
    Keywords: digoxin ; pharmacokinetics ; response kinetics ; three-compartment model ; serum digoxin kinetics ; systolic time intervals ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A study designed to investigate the relationship between the pharmacokinetics of digoxin and a measure of its pharmacological effect has been conducted. Serum digoxin concentrations and systolic time intervals were measured concurrently in 12 normal male volunteers following a 1.0 mg i.v. bolus injection. The averaged serum digoxin concentration- time and response-time data were analyzed pharmacokinetically using a three-compartment open model and nonlinear least- squares fitting. When only the serum level-time data were analyzed, a close relationship was found between calculated digoxin levels in the slowly distributing (deep) peripheral compartment and response of the heart to digoxin, as measured by changes in the QS2 index δQS2I. Although it was not possible to distinguish clearly a linear from a nonlinear relationship between digoxin levels in the deep compartment and δQS2I, the nonlinear relationship gave the best overall fit when both serum digoxin and δQS2I data were fitted simultaneously. The simultaneous fityielded a total body clearance of digoxin of 3.6 ml/min/kg and a terminal t1/2 of 42 hr.
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  • 53
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 87-95 
    ISSN: 1573-8744
    Keywords: clonazepam ; in vivo biotransformation ; 7-amino metabolite ; pharmacokinetics ; monkeys ; anticonvulsants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic behavior of the 7-amino metabolite of clonazepam administered exogenously and formed endogenously from the parent drug was studied in a group of rhesus monkeys using constant rate intravenous infusions. Plasma levels of the 7-amino metabolite and/or clonazepam were determined with a GC-CI-MS method. The biological half-life of the 7-amino metabolite (2.2 ± 1.0 hr) was shorter than that of clonazepam (4.9 ± 0.2 hr). Total body clearance of the metabolite (0.83 ± 0.16 liters/hr/kg) was larger than that of the parent drug (0.55 ± 0.09 liters/hr/kg). The kinetics of in vivo biotransformation were described by a two- compartment model in which formation and disposition of the metabolite follow first-order processes. The fraction of a dose of clonazepam appearing in the systemic circulation as 7-amino metabolite was 0.70 ± 0.30. This value may underestimate the actual fraction formed, if the metabolite is susceptible to first- pass metabolism following in situ formation.
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  • 54
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 265-274 
    ISSN: 1573-8744
    Keywords: furosemide ; indomethacin ; prostaglandin ; pharmacokinetics ; pharma-codynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged furosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.
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  • 55
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 453-462 
    ISSN: 1573-8744
    Keywords: pheneturide ; antiepileptics ; pharmacokinetics ; TLC-UV densitometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of pheneturide (a decarboxylation product of phenobarbital), used to prevent psychomotor seizures for many years, was studied in normal human volunteers. To measure the drug in plasma and urine, a highly sensitive and reproducible thin-layer chromatography-reflectance spectrophotometric assay was developed. The results show that pheneturide follows first-order kinetics in the dose range studied. Its half-life after single doses is 54 hr (range 31–90), and its total body clearance (100% nonrenal) is 2.6 liters/hr (range 1.73–3.59). After repetitive administration, half-life is 40 hr (but clearance remains unchanged because of a lower volume of distribution). Because of the long half-life, repetitive administration results in a continuous steady-state level and makes this drug (kinetically) ideal for long-term use.
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  • 56
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 471-479 
    ISSN: 1573-8744
    Keywords: metoprolol ; α-OH-metoprolol ; active metabolites ; pharmacokinetics ; β- blocking effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The plasma levels and the β- blocking effect of metoprolol and its active metabolite α- hydroxymetoprolol have been studied after i.v. bolus injections of the substances to dogs. For both substances the β- blockade increased with the dose, and there was a linear relationship between percent reduction in exercise heart rate and the logarithm of plasma concentration. The dose of the metabolite, however, had to be 5 times higher than that of metoprolol to induce the same degree of β- blockade. Because of differences in the volume of distribution, 2.0 liters/kg for α- OH-metoprolol and 3.5 liters/kg for metoprolol, the 5 times higher dose of α- OH-metoprolol resulted in 10 times higher plasma levels of the metabolite than of metoprolol. α- OH-Metoprolol was more slowly eliminated (t1/2∼7.0 hr, total body clearance ∼3.5 ml-kg−1-min−1) than metoprolol (t1/2∼2.0 hr, total body clearance ∼20.0 ml-kg−1-min−1). Approximately 5% of an i.v. dose of metoprolol was metabolized to α- OH-metoprolol. The half-life of the endogenously formed metabolite was the same as after an i.v. dose of the compound.
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  • 57
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    International ophthalmology 1 (1979), S. 109-122 
    ISSN: 1573-2630
    Keywords: Photocoagulation ; Non-linear effects ; Physics ; Morphology ; Nd glass Q-switched laser ; Scanning electron microscopy ; Chamber angle ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Working at a power density above optical breakdown threshold, irradiation effects upon the angle of the anterior chamber of the Macaca speciosa monkey by a Nd glass Q-switched laser, have been analysed with scanning electron microscopy. Two different damage effects can be identified: openings of Schlemm's canal and the creation of a cyclodialysis, that is opening the uveoscleral outflow routes; the latter may be a more effective one than the former. Also a third mechanism, namely a structural alteration of the trabecular meshwork, at the molecular level by laser action, has been inferred. The physical effects leading to optically induced mechanical damage are discussed. Applicability of such effects upon the morphological findings described here, is limited and to a greater part speculative. A better definition of the physical parameters, required for optimal therapeutical damage effects in the treatment of the wide angle glaucoma may be obtained by trial and error methods, which are guided by the results of electron microscopical analyses of samples obtained from in vivo and in vitro experiments.
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  • 58
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    Journal of Morphology 159 (1979) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 59
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    Journal of Morphology 159 (1979), S. 1-15 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Fully mature adult Eisenia foetida sensory buds are abundant on the prostomium and the first segment. In subsequent segments they are restricted to the anterior half where they form a single row aligned with the setae and encircling the worm. In the more posterior regions of the worm the buds are widely separated and fewer. The surface of each bud is a raised circular or oval area from which 15 to 100 so-called sensory hairs arise, being cylindrical and apparently flexible. The number of these projections decreases toward the posterior end of the worm.In worms newly emerged from egg cocoons, the general pattern of distribution and external form of sensory buds resembles that of adults, but the buds are much fewer and smaller than in adults. Although these worms emerge with their definitive adult number of segments, new buds and additional sensory projections are formed during post hatching development.
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  • 60
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    Journal of Morphology 159 (1979), S. 67-79 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The distribution and morphology of phagocytic (Type II) supraependymal cells residing within the third ventricle of the guinea pig were investigated by scanning electron microscopy. Type II supraependymal cells were restricted to nonciliated regions of the ventricle. They were most numerous on the choroid plexus, abundant within the infundibular recess and were present on the ventricular floor in the region of the median eminence. Morphologically, they were characterized by a soma from which pseudopodia-like processes extended to the subjacent ependyma. Type II cells varied in configuration according to their location. Those residing on the choroid plexus typically had irregular somas and possessed processes that generally terminated in finger-like extensions. In contrast, cells on the ventricular floor and within the infundibular recess were stellate and possessed processes that terminated in fan-like cytoplasmic expansions. There were no differences noted in the frequency, distribution or morphology of Type II supraependymal cells in male and female animals. Furthermore, cell frequency did not appear to vary in relation to the estrous cycle. The data suggest that the pleomorphism exhibited by Type II supraependymal cells may reflect adaptations to diverse environmental conditions present within different regions of the third ventricle.
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  • 61
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    Journal of Morphology 159 (1979), S. 81-87 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Study of the fine structure of the macronucleus in Euplotes eurystomus, a ciliate protozoon, during various stages of the cell division cycle has yielded new information about intranuclear helices. They are frequently observed at the periphery of chromatin bodies or next to the nuclear envelope, and they appear to be a constituent of nucleoli. The fibril that forms a helix is about 11-15 nm thick, and torus profiles of helices cut in cross section are about 35 nm in diameter. In substructure the helix is composed of a thin strand 3-5 nm thick which is coiled to form the 11-15 nm fibril; so the helix is a super-coiled structure. The intranuclear helices are present in the macronucleus throughout the cell cycle. They do not show obvious changes of relative abundance nor changes of relative localization in the nucleus, with one exception: they were never observed in the diffuse zone of replication bands. Evidence is presented indicating that nuclear helices migrate to the cytoplasm through nuclear pores. Although the chemical composition of the Euplotes intranuclear helices is unknown, information in the literature on similar helices in Amoeba indicates that they contain RNA and not DNA. The observations on Euplotes helices are consistent with a concept of “packaged” RNA for transport to the cytoplasm.
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  • 62
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    Journal of Morphology 159 (1979), S. 131-143 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Eggs of the turtle Trionyx spiniferus are rigid, calcareous spheres averaging 2.5 cm in diameter. The eggshell is morphologically very similar to avian eggshells. The outer crystalline layer is composed of roughly columnar aggregates, or shell units, of calcium carbonate in the aragonite form. Each shell unit tapers to a somewhat conical tip at its base. Interior to the crystalline layer are two tertiary egg membranes: the outer shell membrane and the inner shell membrane. The outer shell membrane is firmly attached to the inner surface of the shell, and the two membranes are in contact except at the air cell, where the inner shell membrane separates from the outer shell membrane. Both membranes are multi-layered, with the inner shell membrane exhibiting a more fibrous structure than the outer shell membrane. Numerous pores are found in the eggshell, and these generally occur at the intersection of four or more shell units.
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  • 63
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The afferent and efferent components of the facial nerve were traced within the brain stem of Rana catesbeiana, using three different neuroanatomical techniques. Primary afferent fibers could be traced to the spinal tract of trigeminal nerve and to fasciculus solitarius as far caudally as the first or second spinal segment, using silver degeneration methods. Cobalt filling of the entire nerve showed the same distribution of afferent fibers, as well as the filling of the cells within the mesencephalic nucleus of trigeminal, indicating the origin of a proprioceptive component of the facial nerve. Cobalt iontophoresis and horseradish peroxidase experiments showed that the motor nucleus of the facial nerve was located just ventral to the fourth ventricle, and caudal to the motor nucleus of trigeminal. The distribution of afferent fibers to fasciculus solitarius and the spinal tract of trigeminal is similar in some respects to the distribution of afferent fibers from the trigeminal and vagal nerves in the bullfrog. The afferent fibers from the three cranial nerves are found as far caudally in the brain stem as the second spinal segment.
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  • 64
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    Journal of Morphology 159 (1979), S. 331-341 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology of tooth crowns is variable inter-specifically among caecilians. Cusp number and shape, crown dimensions, and crown curvature characterize various species and have both functional and phylogenetic implications. Ichthyophis, Uraeotyphlus, Hypogeophis, and Geotrypetes have bicuspid teeth; Dermophis, Gymnopis, Caecilia, and Typhlonectes monocuspid. Crown morphology as revealed by scanning electron microscopy is associated with prey grasping and, in one case, possible specialization of prey type.
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  • 65
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    Journal of Morphology 160 (1979) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 66
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    Journal of Morphology 160 (1979), S. 7-15 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The structure of contact chemoreceptors in the cibariopharyngeal pump of the moth Trichoplusia ni (Lepidoptera: Noctuidae) is described. Two types of receptors designated A and B are located on the floor of the pump. Two groups of 9-12 A receptors are located in the anterior part of the pump, and two groups of two B receptors are in the posterior part of the pump. Five sensory dendrites extend to the tip of each A receptor and four to each B receptors. Available evidence indicates that these receptors are contact chemoreceptors and do not serve as mechanoreceptors. The receptors are compared to those of other insects.
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  • 67
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    Journal of Morphology 160 (1979), S. 103-119 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Classical light microscopic studies on pigmentation of Fundulus heteroclitus (killifish) indicated that there are three groups of light reflecting cells; one group on the surface of scales reflects white light, while two other deeper groups (the melaniridophores and the stratum argenteum) are iridescent. The results presented here show that: (1) The scale leucophores reflect white light by a Tyndall light-scattering mechanism, by virtue of the presence of randomly oriented organelles of “novel” morphology. (2) The iridophores of the melaniridophores contain stacks of irregularly-spaced, large reflecting platelets which function as an imperfect multiple thin layer interference system. (3) The stratum argenteum consists of a continuous layer(s) of iridophores with reflecting platelets which are so regularly packed as to approach an ideal multiple thin layer interference system. (4) In all three types of light reflecting cells, the dimensions and packing (orientation) of the reflecting organelles satisfactorily account for the chromogenic properties of the cells, including colors as viewed under transmitted, reflected, or polarized light. (5) The spacial relationships between these light reflecting cells and adjoining melanophores are different for each type of light reflecting cell. Furthermore, we propose to replace the term reflecting platelet with refractosome.
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  • 68
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    Journal of Morphology 160 (1979), S. 143-163 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The chloride cells in the interlamellar areas of the gills of young adult, anadromous sea lampreys, Petromyzon marinus L., captured in fresh water undergo structural modification during the adaptation of these animals to sea water. In fresh water the chloride cells are partially overlapped by mucus-secreting superficial cells and contain an extensive reticulum of cytoplasmic tubules, which are confluent with both lateral and basal plasma membranes, numerous mitochondria, a Golgi complex of moderate size, and numerous apical vesicles. Adaptation to sea water results in a retraction of the superficial cells, exposing the entire apical surface of the chloride cells, and a proliferation of both cytoplasmic tubules and mitochondria. Extensive enlargement of the Golgi complex in the chloride cells of these animals suggests the involvement of this organelle in the proliferation of cytoplasmic tubules. The extracellular tracer, ruthenium red, enters the tubules from the lateral or basal intercellular spaces in both freshwater- and seawater-adapted animals but never enters either tubules or vesicles from the apical surfaces, indicating that these are not confluent. The presence of dividing basal cells and newly-forming chloride cells, combined with evidence of degeneration of chloride cells, suggests that there is a turnover of this cell type. Both superficial and basal cells are phagocytic and involved in heterophagy of degenerating chloride cells. This phenomenon occurs in both fresh water and sea water indicating that the chloride cells may be functional in both environments.
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  • 69
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    Journal of Morphology 160 (1979), S. 121-141 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This study consists of a detailed cytoarchitectonic and Golgi analysis of a major tectofugal thalamic nucleus in the red-eared turtle, Pseudemys scripta elegans. Neurons in nucleus rotundus have a unimodal soma size distribution and a common dendritic branching pattern. They have long dendrites which undergo sparse, dichotomous branchings and contribute to dendritic fields that cover a third to half the dimensions of the nucleus. Spicules, 1-2 μ long, and complex appendages, 5-20 μ long, are found with low density on many dendrites in Golgi-Kopsch material. A few cells have beaded dendritic processes. Three cytoarchitectural regions can be differentiated in nucleus rotundus: a shell, a cell-poor region and a core. The shell is a monolayer of somata forming the peripheral boundary of most of the nucleus. The cell-poor region forms a thin zone concentric with and internal to the shell. Shell cells send some of their dendrites concentrically within this zone and others radially into the core region. Core neurons are dispersed within the neuropil of the nucleus and usually have spherical dendritic fields. However, peripheral core neurons have asymmetrical fields, so their dendrites do not extend beyond the shell. Caudomedial and central subregions of the core can be defined on the basis of neuronal density and cytology. Somata in the caudomedial area of the core are densely packed and have slightly darker staining cytoplasm than those in the central subregion. However, their dendrites are similar to those of the central core neurons. There is extensive dendritic overlap between the two subregions.
    Additional Material: 13 Ill.
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  • 70
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    Journal of Morphology 161 (1979), S. 1-21 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: As a part of a continuing study of unusual molluscan tissues, the “chondroid” tissue (Hyman, '67) associated with the anterior and posterior aortae of the slug (Limax maximus) was examined by light and electron microscopy. Unlike the odontophoral tissue of this species (Curtis and Cowden, '77), the “chondroid” tissue comprising the adventitial layer of the aorta consists of large, glycogen-filled cells with characteristic arrays of pores in their plasma membranes resembling those of the “globular” cells (Rogers, '69; Fernandez, '71); “fibrocytes” (Nicaise et al., '66; Baleydier et al., '69; Nicaise, '73); “Blasenzellen” or “Leydig” cells (Wondrak, '69; Stang-Voss, '70; Buchholz et al., '71; Stang-Voss and Staubesand, '71; Wolburg-Buchholz, '72); or “pore” cells (Sminia, '72; Beltz, '77) of other mollusks. The anterior and posterior aortae are very similar in organization, except that the anterior aorta is larger in diameter; its wall is thinner; and it lacks calcification. Both the anterior and posterior aortae possess a loosely organized (incomplete) endothelial layer surrounded by two layers of innervated smooth muscle. The smooth muscle cells possess fibrous surface specializations resembling hemidesmosomes as well as large numbers of tubular or rounded vesicles in association with their plasma membranes. Blood cells (amoebocytes) containing large glycogen deposits and distinctive membrane-enclosed cytoplasmic inclusions can be found occasionally in the walls of the vessels.
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  • 71
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    Journal of Morphology 161 (1979), S. 111-121 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Reticulate scales develop as radial symmetrical anlagen, in contrast to scuttate scales which appear initially as “epidermal placodes.” Unlike scuttate scales whose outer and inner epidermal surfaces elaborate β-and α-type keratins, respectively, reticulate scales elaborate only one type of epidermal surface which has been reported to give an α-type, X-ray diffraction pattern. We find that, histologically and ultrastructurally, this surface differs from either epidermal surface of scuttate scales. The keratinizing cells become filled with long interweaving bundles of α-filaments which aggregate into rather homogeneous α-fibrils. Keratohyalin granules, which have been shown to be associated with other keratinizing regions in the bird, do not form during the keratinization of reticulate scale epidermis.
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  • 72
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    Journal of Morphology 161 (1979), S. 145-155 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The ultrastructure of the parathyroid glands of adult Japanese lizards (Takydromus tachydromoides) in the spring and summer season was examined. The parenchyma of the gland consists of chief cells arranged in cords or solid masses. Many chief cells contain numerous free ribosomes and mitochondria, well-developed Golgi complexes, a few lysosome-like bodies, some multivesicular bodies and relatively numerous lipid droplets. The endoplasmic reticulum is mainly smooth-surfaced. Cisternae of the rough endoplasmic reticulum are distributed randomly in the cytoplasm. Small coated vesicles of 700-800 Å in diameter are found occasionally in the cytoplasm, especially in the Golgi region. The chief cells contain occasional secretory granules of 150-300 nm in diameter that are distributed randomly in the cytoplasm and lie close to the plasma membrane. Electron dense material similar to the contents of the secretory granules is observed in the enlarged intercellular space. These findings suggest that the secretory granules may be discharged into the intercellular space by an eruptocrine type of secretion. Coated vesicles (invaginations) connected to the plasma membrane and smooth vesicles arranged in a row near the plasma membrane are observed. It is suggested that such coated vesicles may take up extracellular proteins. The accumulation of microfilaments is sometimes recognized. Morphological evidence of synthetic and secretory activities in the chief cells suggests active parathyroid function in the Japanese lizard during the spring and summer season.
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  • 73
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The combined techniques of light microscopy, scanning (SEM) and transmission (TEM) electron microscopy were used for the first time to study the structure of unicameral lungs of a Tegu lizard (Tupinambis nigropunctatus). The lungs are prolate spheroid bags with blood supplied by superficial branches of a dorsal pulmonary artery and returned by diffuse, more deeply located veins. The primary bronchus enters the medial aspect near the apex of the lung. The lung wall is composed of trabeculae: (1) arranged in a faviform pattern, (2) forming individual faveoli (gas exchange chambers) which appear deepest in the cranial one-half of the lung, (3) all of which have a smooth muscle core overlain by either a ciliated or nonciliated epithelium. A ciliated epithelium lines the luminal surfaces of the large primary trabeculae and parts of smaller secondary trabeculae; it is composed of cone-shaped cells with ciliated-microvillous surfaces, and of columnar serous secreting cells. Nonciliated epithelium covers the luminal surface of portions of some secondary trabeculae, abluminal surfaces of primary and secondary trabeculae and all surfaces of the small tertiary trabeculae forming the faveoli. The nonciliated epithelium overlies an extensive superficial capillary network. The blood-gas barrier (0.7-1.0 μm thick) is composed of a thin cytoplasmic flange of Type I pneumonocytes, a thick homogeneous basal lamina and an attenuated endothelial cytoplasm. Numerous surfactant-producing Type II pneumonocytes are closely associated with the Type I pneumonocytes. The nonrespiratory ciliated epithelium may function in humidification of air and clearing of the lungs.
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  • 74
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    Journal of Morphology 162 (1979), S. 1-15 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The pineal complexes of the two closely related deep-sea fishes Cyclothone signata and C. acclinidens were compared both qualitatively and quantitatively. Photoreceptor and supportive cells were identified in both species. The deeper-dwelling species, C. acclinidens, had a significantly greater number of photoreceptor-cell outer segment saccules and a higher ratio of receptor cells to nerve fibers in the pineal stalk. It was suggested that these indicate increased photosensitivity of the pineal. Supportive cells were sometimes seen to contain arrays of undulating tubules. The functional significance of these tubules is not understood. A prominent dorsal sac is closely associated with the pineal end-vesicle. Both structures appear to have a common vascular supply suggesting that they are functionally related. Dorsal sac cells contained abundant mitochondria, glycogen, and large filament-like inclusions.
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  • 75
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    Journal of Morphology 162 (1979), S. 77-91 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Diploid tadpoles of the discoglossid frog, Bombina orientalis, possess a distinctive rectangular network of epidermal melanophores. The ontogeny of this network was examined and utilized as a model for the comparison of tissue integrity and cellular interactions in diploid and haploid embryos.During the process of network formation in diploids, a variety of melano-phore-melanophore interactions was observed. These included temporary contacts between neighboring melanophore processes, deviations of processes toward neighboring melanophores, and lateral extensions between closely situated, parallel processes originating from different cell bodies. None of these intercellular interactions were seen in haploid embryos. Haploid melanophores displayed fewer cytoplasmic extensions, appeared to be randomly oriented, and failed to establish the ordered network seen in diploid embryos. It was also discovered that, in comparison with diploid tissues, relative densities of melanophores and epithelial cells were not uniformly regulated in haploid embryos.These findings are interpreted as indicating that haploid embryos possess fundamental cell and tissue defects, and that the “haploid syndrome” is likely based on more than one or a few defective physiological functions.
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  • 76
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A β-keratin pattern, consisting of 30 Å filaments embedded in an amorphous matrix, is formed by fusion of membrane-bound packets with the 70 Å filaments of immature cells. This pattern occurs in the Oberhäutchen and the β-layer. When completely mature, these two components show no cell boundaries. It is suggested that this feature is associated with the process that leads to the separation of outer and inner epidermal generation. Filaments of 100-150 Å embedded in an amorphous matrix form the α-keratin pattern, which occurs in the α-layer only. The lacunar tissue is regarded as consisting of cells resembling immature α-cells, whereas mesos and clear layer show a keratin-like material consisting of 100-150 Å filaments without matrix. This is regarded as a modification of α-keratin. The cells of all components synthesizing α-keratin (α, mesos and clear layer) have the following features in common: (1) the plasma membrane is modified in that its inner leaflet is obscured by the deposition of a marginal layer, and (2) the cells have 0.06-0.1 μm mucous granules containing mucopolysaccharides, which release their content into the intercellular space.Protective and barrier functions of the epidermis are provided by the following features: (1) Oberhäutchen and β-layer merge during final maturation to a homogenous stratum of β-keratin without intercellular spaces. Their function seems to be mechanical protection. (2) The marginal layer of α-keratin containing cells, which decreases in thickness from without inwards, is highly resistant to physical and chemical influences. (3) Mesos granules contain phos-pholipid-lamellae, which are partly discharged into the intercellular space and partly remain within the mesos cells. These lipid lamellae are believed to contribute to the establishment of the permeability barrier. (4) The content of mucous granules may play a role in immunological processes. (5) Tight junctions seal off the intercellular space between the uppermost living cells of the epidermis and contribute to the permeability barrier.
    Additional Material: 1 Ill.
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  • 77
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    Journal of Morphology 159 (1979), S. 17-27 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Eggs of Chelydra serpentina were shifted during incubation between the female producing temperatures of 20°C or 30°C and the male producing temperature of 26°C. In the 20°C and 26°C combination, the stages during which incubation temperature determined sex were stage 14 through stage 16 (stages of normal series, Yntema, '68). In the 30°C and 26°C combination, the temperature sensitive stages for sex determination were stage 14 through stage 19. Incubation at 26°C throughout this period was needed to produce all males. Incubation at 30°C during either the first or second half of the period produced nearly all females; shorter periods of incubation at 30°C were more effective in producing females during the second half of the sensitive period. In the 20°C and 26°C combination, incubation at 20°C or 26°C for parts of the sensitive period produced both males and females. In three of the 57 clutches of eggs used in the experiments, incidence of females was atypically high.
    Additional Material: 10 Ill.
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  • 78
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    Journal of Morphology 159 (1979), S. 117-130 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The purpose of this investigation was to relate the morphology of connective tissues in the mandibular symphysis to the behavioral and experimental evidence for mobility and mechanical stress at the symphysis. The anatomy of the symphysis was examined histologically in 6 mammalian orders encompassing 22 species. Behavioral and experimental evidence of stress during the power stroke of the chewing cycle correspond with stresses at the symphysis implied by the location and orientation of symphyseal connective tissues. These stresses are: (1) dorsoventral shear of the symphysis due to the transfer of force from balancing to chewing sides, (2) bending of the symphysis causing tension along the inferior and compression along superior borders due to torsion on the dentaries from the jaw closing muscles, and (3) antero-posterior shear of the symphysis due to an anteriorly directed stress on the chewing side. Interspecific comparisons suggest that leaf eaters can resist greater dorsoventral shear than fruit or insect eaters, but no correlations exist between diet and bending or antero-posterior shear. This suggests that chewing leaves requires larger biting forces.
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  • 79
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    Journal of Morphology 159 (1979), S. 151-183 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The unusual lymphogranulopoietic bone marrow of the large lungless salamander Plethodon glutinosus was examined by light and electron microscopy. Developing neutrophils, eosinophils, and fat cells were found in large numbers, while lymphocytes of various sizes, plasma cells, plasmablasts, macrophages, pigment cells, and fibroblasts were present in more moderate numbers. Basophils were observed only rarely. Macrophages were found in extravascular locations and did not appear to be associated directly with the walls of the blood vessels supplying the marrow. Both neutrophils and eosinophils seemed to arise from small precursor cells whose ultrastructural features bore a resemblance in some ways to those of mammalian myeloblasts described by Bainton and Farquhar ('66). Developing neutrophils and eosinophils seemed to produce only single populations of specific cytoplasmic granules, rather than both primary (azurophilic) and secondary (specific) inclusions, as are produced typically by mammalian granulocytes. Both eosinophilic and neutrophilic granules were formed in association with Golgi complexes; and eosinophilic granules were much larger, more densely stained, and more regularly rounded in shape than the inclusions of developing neutrophils. Peroxidase activity was associated with the specific granules of neutrophils but seemed to be lacking in the granules of eosinophils. The specific granules of eosinophils were especially unusual because they contained irregularly shaped, lightly stained cores which occasionally displayed a distinctly crystalline substructural organization. The specific granules of basophils also possessed a prominent crystalline organization. The overall appearance of the marrow of Plethodon suggests that it functions not only as a valuable source of neutrophils, eosinophils, and cells of the lymphoid series, but also as a part of the phagocytic system of the animals and as an important repository for fat.
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  • 80
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The central nervous system of the sessile barnacle, Semibalanus cariosus (Pallas), has been studied with the particular aim of determining the locations of neuron somata in relation to peripheral nerves. This was accomplished by tracing peripheral nerves using dissection and methylene blue staining techniques, histological methods, and by permitting cobaltous chloride to diffuse via axons into ganglia (“backfilling”).The neuron maps resulting from the study reveal some well-defined sub-systems, a considerable degree of functional clumping of neuron somata, and some unexpected projections of neurons in the CNS. Neurophysiological studies based on these findings are in progress.
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  • 81
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    Journal of Morphology 159 (1979), S. 343-353 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effect of germanium on the secretion of siliceous spicules by the freshwater sponge Spongilla lacustris was investigated by exposing germinating and hatching gemmules to varying concentrations of germanium (Ge) in the presence of silicon (Si). Results were analyzed quantitatively and qualitatively and demonstrate that a [Ge]/[Si] (= molar ratio) of 1.0 completely inhibits silicon deposition. Intermediate ratios (0.5, 0.1, 0.01) which are permissive to spicule appearance result in fewer, shorter, and thinner spicules, in proportionately fewer microscleres, and in short bulbous megascleres. The size of the bulb increases with increasing [Ge]/[Si], while the length of the bulbous megascleres decreases with increasing [Ge]/[Si]. Microscleres do not demonstrate these graded responses suggesting that they are secreted in an all or none manner. Swellings produced in pond water and bulbs produced in germanium appear to decrease in size with time indicating a spreading of the accumulated silica. The effect of germanium on spicule secretion can be partially explained by its ability to uncouple the growth in length of the axial filament from the growth of the surrounding silicalemma. Under these conditions excess silicalemma is produced in which silica accumulates as bulbs in short spicules. Continuous exposure to Ge is necessary to produce this altered morphology. It is conjectured that the bulbs may be retained due to an inhibition of spreading. which in turn may be caused by the incorporation of germanium into the silica.
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  • 82
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Four differentiated Malpighian tubules (primary tubules) extend from the junction of the midgut and hindgut in newly hatched Periplaneta americana. Secondary tubules begin to develop near the base of the primary tubules before hatching and successive nymphal molts. The newly initiated tubules undergo cell division and extensive elongation through the middle of the following intermolt period. During this time, the cells of the distal, middle, and lower middle tubule regions are surrounded by a cellular sheath, have few cytoplasmic processes extending along their basal surfaces, have a small or nonexistent lumen, and contain extremely dilated cisternae of endoplasmic reticulum. The cellular sheath differentiates into the muscle which coils around the mature tubule. Tubules which begin development toward the end of one intermolt period begin to undergo cytodifferentiation toward the end of the next intermolt period. By the middle of an additional intermolt period, the basal infoldings and microvilli of cells in the distal, middle, and lower middle regions have the conformations typical for those regions in differentiated tubules; granular concretions and stellate cells are present within the middle region of the tubule.
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  • 83
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This investigation was undertaken to examine the observations of Becker ('72) pertaining to the electrical facilitation of partial limb regenerative responses by means of Ag-Pt wire couples applied to the limb stumps of young, forelimb-amputated white rats. Additionally, in order to examine the possible role of mechanical effects of such device implantations, we have employed uncoupled devices delivering no current or potential difference. In the present experiments, in response to coupled device implantation, cartilage and bone were actively formed in the vicinity of the Pt electrode tip. These tissues contributed to the lengthwise extension of the limb and to the partial restoration of the distal humeral extremity. In limbs bearing the uncoupled electrical devices, qualitatively similar responses were noted, but osteogenesis was diminished in extent compared to that seen in limbs bearing the active or coupled devices. It is therefore necessary to consider the role of mechanical factors in the elicitation of the observed regenerative responses. Myogenesis was enhanced in electrically stimulated limbs, but not in those rats bearing uncoupled devices.
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  • 84
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    Journal of Morphology 160 (1979), S. 33-73 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The most complete account of the hind leg muscles of the kiwi was published a century ago by Sir Richard Owen, in his seventy-fifth year. This extensively-cited work has several omissions and errors, and while certain of these were corrected by subsequent authors, sufficient uncertainty remains to warrant a reinvestigation. In the present study a detailed description of the hind leg musculature is given, based upon dissections of two frozen specimens. An indication of the possible function of each muscle is given by assessing its size, action, and fiber-arrangement, together with tentative data on the relative abundance of twitch and tonus fibers.The correlation between surface features of bones and muscle attachments is investigated with a view to interpreting palaeontological material. Although the limb and pelvic bones are marked by numerous features which suggest muscle attachments, relatively few can be positively identified with specific muscles. Only 23% of the muscle origins and insertions can be identified, and, with three possible exceptions, no indication of relative size is given by the scars. The possibility of being able to reconstruct the musculature of the kiwi from its skeletal anatomy, much less that of its extinct relatives, is remote.
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  • 85
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    Journal of Morphology 159 (1979), S. 393-425 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Branchial food traps are regions of specialized secretory tissue in the tadpole pharynx, where suspended food particles are trapped in mucus.Light and scanning electron microscopy were used to study branchial food traps from larvae of ten anuran families (36 species). Most anuran larvae from “advanced” (suborder Neobatrachia) families (e.g., Hylidae, Ranidae, Bufonidae) have distinct secretory pits at the posterior margins of the branchial food traps and secretory ridges elsewhere on these surfaces. The apices of columnar PAS-positive, secretory cells are exposed on the floors of the secretory pits or in rows at the tops of the secretory ridges (secretory zone).Tadpoles from most “archaic” (suborder Archaeobatrachia) families (Ascaphidae, Discoglossidae and Pelobatidae) either lack secretory pits, or have them poorly defined. They also lack secretory ridges but have columnar, mucus-secreting cells whose apices are exposed in a seemingly random fashion in the branchial food traps. Rhinophrynus (Archaeobatrachia: Rhinophrynidae) has secretory ridges, but the apices of secretory cells are not arranged in rows at the tops of the ridges; instead they erupt singly or in small clusters on the epithelial surface, in a pattern similar to that in Ascaphus, the discoglossids and the pelobatids. It is proposed that the generalized condition for the branchial food trap mucosa is one where the apices of secretory cells are exposed haphazardly on a flat epithelium and the derived condition is one where the surface is organized into ridges. The morphology of the branchial food traps in Rhinophrynus suggests that, phylogenetically, ridges preceded the coalescing of secretory cell apices into distinct rows.Pipidae and Microhylidae have unique patterns in the gross and microanatomy of their branchial food traps specific to their families.Branchial food trap morphology relates to diets of tadpoles as well as to taxonomy. Obligate macrophagous (e.g., carnivorous) tadpoles, irrespective of family, tend to have reduced branchial food traps, regularly lack secretory ridges and, in extreme cases, lack columnar mucus-secreting cells. Obligate microphagous forms (midwater suspension feeding of Xenopus, microhylids and Agalychnis), have straight parallel secretory ridges with narrow secretory zones and shallow troughs between the ridges.Secretory ridges may help to form mucus strands in which food particles are trapped, but they are not essential for planktonic entrapment. The hydrodynamic implications of the various topographic patterns remain unclear.
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  • 86
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    Journal of Morphology 160 (1979), S. 1-5 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Tactile hairs, small chemoreceptor pegs, thick-walled chemoreceptors, thin-walled chemoreceptors of several types, coeloconic sense organs and campaniform sense organs are present on the flagellum of a stonefly, Allocapnia recta (Claassen).
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  • 87
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    Journal of Morphology 160 (1979) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 88
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 161 (1979), S. 23-38 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Glycogen metabolism has been studied during the development of the early chick embryo, at the cytochemical and ultrastructural levels. Two waves of glycogen synthesis and breakdown have been found. In the first, free clusters of glycogen particles are synthesized at late oogenesis. These clusters are found later in invaginations of the membrane of vesicles containing a floc-cular material (FLOV). The glycogen clusters are degraded there during ovulation and the first hours in the oviduct. The second wave of glycogen synthesis begins before cleavage, reaching a maximum at mid-uterine age. This second wave occurs in another type of vesicle (GLYV), which eventually disintegrates releasing free clusters of glycogen granules. This glycogen is degraded in membranous structures containing a floccular material, as in the first wave of degradation. The degradation ends at the late uterine stages, and at the same time numerous ribosomes are formed. This period corresponds to area pellucida formation, which probably depends on the energy liberated during the second wave of glycogen degradation.
    Additional Material: 2 Ill.
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  • 89
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    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 161 (1979), S. 79-109 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The hindgut of the semi-terrestrial tardigrade, Milnesium tardigradum was examined with light and electron microscopy. The hindgut consists of a cloaca and an anterior hindgut. It is delineated anteriorly by the pylorus into which four Malpighian tubules empty and posteriorly, by a broad cloacal slit. A single oviduct enters the hindgut at the junction between the cloaca and the anterior hindgut. Two pairs of muscles insert on the cloaca and anterior hindgut respectively. Electron microscopic observations demonstrate that the anterior hindgut is a specialized transporting epithelium. The luminal surface is covered by a thin layer of cuticle which penetrates into channel-like invaginations. Numerous mitochondria are concentrated apically. The basal and lateral surfaces are also folded. The cells are joined apically by deep tight junctions and a simple basal lamina lines the entire hindgut. The cloaca which receives the contents of the gut and Malpighian tubules as well as gametes of the reproductive tract is a transitional organ that exhibits several characteristics of the hypodermis and anterior hindgut. The cuticle of the cloaca changes sequentially from the complex structure of the integument to a simple layer of the anterior hindgut. The function of the hindgut is discussed with emphasis on the possible response of the anterior hindgut to a hypoosmotic habitat, evaporative water loss during the induction of anhydrobiosis and low oxygen tension.
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  • 90
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 161 (1979), S. 123-143 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Blood follicles of the earthworm Amynthas are hemoglobin-containing, sac-like dilatations of blood vessels which connect to the general circulation. Grape-like clusters of follicles are found posterior to the pharynx, among tufts of micronephridia, and single follicles are located among cells of the pharyngeal gland. In Lumbricus, follicles take the form of simple swellings and irregular-shaped diverticula of nephridial capillaries.The fundamental structure of the wall of follicles and of vessels in both genera is the same and consists of two layers: an extracellular vascular lamina and an outer (coelomic) covering of smooth muscle-like myoperithelial cells. Hemocytes may be free and circulating or they may facultatively attach to the vascular lamina as littoral cells, constituting an incomplete endothelium-like surface. Hemocytes that appear to be in the process of attaching or detaching are rounded, while adherent cells are flattened and elongate. Free and littoral hemocytes actively endocytose packets of circulating extracellular hemoglobin.Hemocytes within follicles possess radiating cell processes which also endocytose hemoglobin. Although these cells were presumed to secrete hemoglobin, staining with 3,3′-diaminobenzidine confirms the presence of hemoglobin only within pinosomes and not within protein-synthesizing or packaging organelles. The presence of hemosiderin-like bodies suggests that follicular hemocytes catabolize hemoglobin.Blood follicles apparently provide a means of significantly increasing cell-surface area for hemoglobin processing, without substantially increasing the volume and pumping load of the circulatory system.
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  • 91
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 161 (1979), S. 211-219 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The nucleoli of rat liver cells duplicate in great detail the lifelong series of reorganizational changes encountered in kidney and intestinal epithelial cells. The ultrastructural components of the large, loosely organized polymorphous nucleoli, which are dominant in the rapidly multiplying stem cells of embryos, are readily accessible for chemical activities. Smaller, more compact amphinucleoli are dominant in more mature cells, which were characterized by Smetana ('70) as “idling” cells, showing slowly continuing ribosome formation and RNP synthesis. In older cells bipartite nucleoli become dominant and are reorganized in increasing numbers from the younger amphinucleoli. These, however, are not replaced in equal numbers from the shrinking pool of polymorphs of young cells which have greatly reduced mitotic potential. Paralleling the shifts in dominant nucleolar types, the high level of protein synthesis declines in older cells not only in the quantity of proteins synthesized but also in kinds of enzymes produced. These fail to meet the structural and functional requirements of aging cells leading ultimately to the onset of age-related degenerative changes. Again it is noted that separation of the karyosomal DNA from the plasmosomal RNA-protein complex of the nucleolus may lead to possible breakdown of the DNA-dependent RNA-protein transcription system ultimately bringing protein synthesis to a very low level in the senescent animal.
    Additional Material: 1 Ill.
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  • 92
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The heart of Crocodylus porosus is described, and deemed to be typical of living crocodilians after examination of the hearts of Alligator mississippiensis, Caiman crocodilus ssp., Crocodylus johnstoni and Crocodylus n. novaeguineae. Some inconsistencies between the anatomy and supposed patterns of blood flow are discussed. The crocodilian heart is compared with, and seen as an advancement of, the heart of non-crocodilian reptiles. The varanid ventricle is re-examined, as it appeared to contain many crocodilian features, along with the ophidian characteristics described previously. The broad similarities within the three groups are interpreted as adaptations towards a high pressure systemic circulation. Consequently varanids and snakes show the same left and right ventricles, as do crocodilians and birds. The evolution of the complete interventricular septum of crocodilians and birds appears to have involved three major trends: firstly, the development of a high pressure left ventricle and the fusion of most of the combined atrio-ventricular valve to the ostium of the right systemic artery; secondly, a line in which right to left shunting became gradually redundant and the vertical septum was completed to the aortico-pulmonary septum (giving rise to the avian ventricle); and thirdly, a line in which right to left shunting became increasingly important, and the vertical septum completed to the interaortic septum (giving rise to the crocodilian ventricle). Perhaps the crocodilian ancestry included a crocodile that was far more aquatic than any extant species.
    Additional Material: 8 Ill.
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  • 93
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 161 (1979), S. 337-345 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In considering primate and hominoid phylogeny, the fundamental position assigned to opossums is explained partially by the characteristic morphology of their hands and feet. One of the main functional features of the human hand is the ability to make a stabilized arch of the finger. Because the extensor assembly plays a key role in establishing an arched finger, the extensor systems of the digits of both the hands and feet were studied in two species of opossum, Philander opossum and Didelphis marsupialis.In the foot, two extensor tendons join in each toe to form one tendinous plate, which inserts onto the base of the second phalanx. Lumbricals join this plate along the tibial side, and interosseus insertions are found, although a true interosseus wing is lacking. At the proximal interphalangeal level, a terminal tendon takes its origin from this tendinous plate. This terminal tendon is oval in cross-section and contains elastic structures. Oblique bands arise from this terminal tendon and run proximally along the proximal interphalangeal joint inserting onto the base of the first phalanx. There are elastic structures in the flexor tendon on the dorsal side near its site of insertion.In the hand, the main extensor tendons are arranged differently and the interossei contribute substantially to the extensor assembly. Otherwise, the extensor assembly of the hands and feet are quite similar. The function of the so-called paratendinous intravaginal flexors is discussed as are evolutionary aspects of the extensor assembly.
    Additional Material: 12 Ill.
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  • 94
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 162 (1979) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 95
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 162 (1979), S. 211-219 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: New schemata of the liver are presented to discuss the combination of the three kinds of liver lobules known until today in a chalk-talk-manner. Terminology is also discussed. Further investigations are needed involving the construction and the vascular pattern of compound lobules of the three individial lobules of the liver in different species.
    Additional Material: 7 Ill.
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  • 96
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    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 161 (1979), S. 323-335 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The blood supply of muscle spindles was studied in serial cross sections in macaque, cat, rabbit, guinea pig, mouse and pigeon muscles which had been incubated in a medium containing 3,3′ diaminobenzidine. Lumina of blood vessels were recognized by the reaction product that was localized within erythrocytes. The outer capsule was well vascularized, but few or no capillaries were seen in the periaxial space. The inner spindle capsule, which closely invests the axial bundle, was rarely contacted by periaxial capillaries at the equator and juxtequator. Capillaries occurred more frequently adjacent to intrafusal fibers at the polar region and beyond the end of the outer capsule. Shorter diffusion distances and, usually, higher capillary densities were found at the polar region than at the spindle midsection. This suggests that transcapillary exchange at the polar segment is nearer to conditions prevalent in extrafusal muscle than elsewhere in the spindle, provided the inner and outer capsules are not less permeable at the poles than at the midsection. Differences in blood supply among mammalian species appear to be related to receptor size.
    Additional Material: 4 Ill.
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  • 97
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    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 162 (1979), S. 67-75 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The role of dying cells in the optic stalk in relation to retinal fiber migration was investigated in the chick embryo. Cell death was analysed at various stages of development by counting pycnotic nuclei and also by the Gomori acid phosphatase reaction, while nerve fibers were visualised by the Bodian method. A wave of cell death, beginning in the neural retina at stage 18 and advancing with time through the stalk towards the diencephalon, occurred simultaneously or slightly prior to differentiation and migration of ganglion cell axons. Cell death stopped and gliogenesis occurred in the stalk after penetration by retinal fibers. Cell death occurred in the stalk even when fiber penetration was prevented by optic cup ablation. In this case, necrosis ensued until almost complete degeneration of the stalk, usually within three days after the operation, and gliogenesis did not occur. As the stalk degenerated, its cells became heavily pigmented. These observations suggest that the onset of cell death in the optic stalk is determined prior to and independently of retinal fiber penetration. On the other hand, cessation of cell death and subsequent gliogenesis occur only in the presence of ingrowing optic fibers.
    Additional Material: 1 Ill.
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  • 98
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Somatic portions of gonads in two phanerozonian sea-stars, Ctenodiscus crispatus and Hippasteria phrygiana, were similar in all aspects of gross structure and histology seen previously in both forcipulate and spinulosan asteroids. For the first time, detailed ultrastructural observations have been made of cells and tissues that reveal several features believed to be of universal occurrence in the gonads of asteroids. These include flagellated-collar cells in the visceral peritoneum and other coelomically derived epithelia, muscular-flagellated-collar cells in the visceral peritoneum and genital coelomic (perihaemal) sinus, the digestion of collagen fibers by cells in the connective tissue layer, and the intimate relationship of the genital haemal sinus and the entire germinal epithelium.Structural and functional compartmentalization are discussed in relation to major activities of the gonad throughout the annual reproductive cycle. The distinctive ultrastructure and current generation of flagellated-collar cells found in the visceral peritoneum are analyzed relative to their role in nutrient transport to gonadal tissues. The single flagellum of each flagellated-collar cell beats in coordination with those on neighboring cells to produce extremely rapid, oriented currents of coelomic fluid. The form of beating in an individual flagellum is planar, and the resulting synchronized activity of many adjacent flagella is non-metachronal; both of these characteristic aspects of current production have, thus far, been encountered together only in the Echinodermata. Flagellated-collar cells are efficient in generating currents which mix contents of the coelomic fluid, and they can presumably supply themselves with nutrients. It is concluded that nutrients so obtained are generally not passed through the wall of the gonad to the germinal epithelium and, as a result, have little to do with nutrition of somatic and germinal cells of the germinal epithelium. Alternatively, well-developed genital portions of the haemal system of the sea-star are advanced as the major channels supplying nutrients to germinal epithelia during gametogenesis.
    Additional Material: 1 Ill.
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  • 99
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 162 (1979), S. 221-247 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The light and electron microscopic structure of the pineal complex of the domestic goose was studied. The complex is tubulofollicular but there is no direct connection between the constituent system of ducts and the third ventricle of the brain. Within the pineal, blood vessels accompanied by sympathetic nerve bundles are confined to the connective tissue. Other nerve fibers and occasional nerve cell bodies, however, do occur among the pineal cells.Three basic pineal cell types were distinguished: (1) elongate epithelial cells which are arranged around follicles and ducts and resemble degenerate photo-receptor cells; (2) intramural supportive cells which are interspersed with elongate epithelial and intramural supportive cells; and (3) small supportive cells which lie between the bases of the elongate epithelial and intramural supportive cells. The follicular structure, vascularization, presence of secretory granules, and the nature of the elongate epithelial cells indicate that the pineal complex is primarily endocrine though a possible photoreceptive function cannot be ignored. Vesicles, 100-300 and 40-100 nm wide, were found within nerves and intramural supportive cells. The larger vesicles, present in pineals collected in the night, probably contain peptidic hormones. The smaller vesicles present in both day and night samples probably contain aminergic hormones.
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  • 100
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cell surface coats are important in adhesion and other cellular activities. The lamprey egg possesses a surface coat that has been divided into two morphologically and functionally distinct regions. The amorphous apical tuft forms a cap over the animal pole, while the elaborately-textured adhesive coat covers the ventral two-thirds of the egg. This latter area is composed of saccules that form rosettes over the egg surface and is derived from the remains of specialized follicular cells which break down during ovulation. The adhesive qualities of these coats may be inhibited or abolished by various proteins and sulphydryl-blocking agents, thereby implicating, as a possible source of this adhesion, classes of acid and sulphated glycoproteins and glycosaminoglycans which occur on the egg surface.
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