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  • 1990-1994
  • 1985-1989  (1,459)
  • 1955-1959
  • 1986  (1,459)
  • Cell & Developmental Biology  (1,316)
  • pharmacokinetics  (143)
Material
Years
  • 1990-1994
  • 1985-1989  (1,459)
  • 1955-1959
Year
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 57-60 
    ISSN: 1432-1041
    Keywords: nifedipine ; pharmacokinetics ; oral contraceptives ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of Nifedipine were measured following single oral doses of Nifedipine Slow Release (Adalat Retard) on three separate occasions to young, healthy volunteers of both sexes. Intra- and inter-subject variability were assessed by comparing the pharmacokinetic parameters, AUC, Cmax and T50%AUC. Interindividual variability was less than that observed in other studies with the betablockers, metoprolol and propranolol and there was no evidence of differences between the sexes.
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  • 102
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 30 (1986), S. 61-68 
    ISSN: 1432-1041
    Keywords: iloprost ; prostacyclin analogue ; pharmacokinetics ; platelet aggregation ; healthy male volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of the prostacyclin analogue, iloprost, were measured by antibody/GC/MS in healthy male volunteers given 1 and 3 ng/kg per min i.v. for 45 min, and 1 µg/kg p.o. Following i.v. infusion, the steady-state plasma levels of iloprost were strictly dose-dependent (46±8 pg/ml and 135±24 pg/ml). The disposition was biphasic with half-lives of 3–4 min and 0.5 h. After oral administration, absorption of the drug was extremely rapid, the maximum plasma level of 251±32 pg/ml being achieved after 10±6 min. The bioavailability was 16±4%. Platelet aggregation induced by 2 µM ADP was reduced by 53% and 68% at the end of the two different infusions, and by 68% 15 min after p.o. administration. The ex-vivo inhibition of platelet aggregation by iloprost was not affected by preceding drug treatment. The cAMP content of platelets was increased by a factor of 2.5 at the end of the infusions and to a lesser extent 15 min after oral dosing. A slight increase in heart rate occurred during the infusion and within 30 min after oral administration; blood pressure was virtually unaffected. Except for transient side-effects (facial flush and headache) no adverse reactions were observed.
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  • 103
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 75-77 
    ISSN: 1432-1041
    Keywords: methysergide ; methylergometrine ; first-pass metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy men were given 1.0 mg methysergide maleate intravenously and 2.7 mg methysergide maleate orally in a cross-over study. The systemic availability of methysergide was only 13%, most probably due to a high degree of first-pass metabolism to methylergometrine. We also found evidence of extrahepatic clearance of methysergide. After oral administration the plasma concentrations of the metabolite were considerably higher than those of the parent drug and the area under the plasma concentration curve (AUC) for methylergometrine was more than ten times greater than for methysergide. Our findings may be relevant to the treatment of migraine if methylergometrine contributes to the effect of methysergide. Methylergometrine had a significantly longer elimination half-life than methysergide (223±43 min vs 62.0±8.3 min and 174±35 min vs 44.8±8.1 min in the oral and intravenous studies respectively).
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  • 104
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 30 (1986), S. 89-92 
    ISSN: 1432-1041
    Keywords: clotiazepam ; liver cirrhosis ; renal insufficiency ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (Vz) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2h). There were no significant differences between renal failure and control patients in clotiazepam Vz, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.
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  • 105
    ISSN: 1432-1041
    Keywords: temazepam ; liver disease ; elimination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the newer 1, 4 benzodiazepine temazepam were evaluated in 16 healthy subjects aged 18–92 years and in 15 cirrhotic patients, to ascertain the effect of ageing and liver disease. The data were analysed both by classic two compartment and by non-compartmental methods. The mean elimination half-life in the control subjects was 15.5 h, considerably longer than previous estimates. No correlation was found between age and pharmacokinetic parameters. The cirrhotic group showed no statistically significant difference in the pharmacokinetic parameters nor in the urinary recovery of the dose from the control group. Temazepam plasma protein binding was assessed in a second group of 9 cirrhotics of similar severity to the main group and in matched controls. When these binding data were applied to the mean clearance data, a modest although not statistically significant, reduction in free drug clearance was observed in the cirrhotic group. This study adds further support to the observation that drugs which undergo ether glucuronidation have normal elimination patterns in patients with liver disease. Temazepam may prove to be a useful hypnotic sedative in patients with liver disease.
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  • 106
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    European journal of clinical pharmacology 30 (1986), S. 83-88 
    ISSN: 1432-1041
    Keywords: mexiletine ; cirrhosis of the liver ; antiarrhythmic agents ; pharmacokinetics ; intravenous administration ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the effects of cirrhosis of the liver on the pharmacokinetics of mexiletine a single i.v. dose of 200 mg was administered to six cirrhotic patients and to six healthy controls. The distribution of mexiletine in both study groups was similar, as indicated by similar values of V1 and Vss, but it tended to occur more slowly in the cirrhotics. The plasma protein binding of mexiletine was unchanged in the patients with cirrhosis. The elimination of mexiletine was markedly retarded in the cirrhotics, as indicated by its lower total clearance (2.31 vs. 8.27 ml/kg/h,) lower total elimination rate constant (0.059 vs 0.353 h−1), and longer elimination half-life (28.7 vs 9.9 h). The antipyrine half-life was 38.3 h in the patients and 14.7 h in the controls. One healthy volunteer had a Morgagni-Stokes-Adams type of syncopal attack 5 min after administration of mexiletine due to disturbance of AV conduction induced by the drug. Thus, on a pharmacokinetic basis the loading dose of mexiletine need not be modified in cirrhotic patients, whereas the maintenance dosage should be reduced to one fourth — one third of the usual dose.
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  • 107
    Electronic Resource
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    European journal of clinical pharmacology 30 (1986), S. 109-112 
    ISSN: 1432-1041
    Keywords: ceftriaxone ; intramuscular ; pharmacokinetics ; steady-state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state pharmacokinetics and tolerance of ceftriaxone after multiple i.m. doses of 0.5 and 1 g q12 h for 3.5 days were investigated in 12 healthy, adult volunteers. Ceftriaxone was rapidly absorbed after i.m. administration with mean peak times ranging from 1.3 to 1.9 h. Steady-state plasma concentrations were apparent after the third dose of both dosage regimens, with trough plasma concentrations of 24±6 and 39±8 µg/ml (mean±SD) after the 0.5 and 1 g q12 h regimens, respectively. Multiple i.m. administrations of ceftriaxone did not alter its elimination half-life; however, small increases were observed in the plasma clearance and volume of distribution at the 1-g regimen. These increases were attributed to the non-linear binding of ceftriaxone to human plasma proteins, and are therapeutically unimportant. Ceftriaxone was well tolerated and serious or lasting adverse reactions were not encountered in the study.
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  • 108
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    European journal of clinical pharmacology 30 (1986), S. 121-123 
    ISSN: 1432-1041
    Keywords: dezocine ; opioid analgesics ; pharmacokinetics ; healthy volunteers ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous (IV) dezocine, and bioavailability of intramuscular (IM) and subcutaneous (SQ) dezocine, were evaluated in healthy male volunteers. Elimination half-life following 5, 10, and 20 mg IV doses averaged 2.6–2.8 h, and was independent of dose. Clearance decreased slightly, although significantly, with dose. After Deltoid IM injection, dezocine was rapidly absorbed (peak level: 0.6 h after dose), with bioavailability 97%. Thus dezocine has extensive distribution, high clearance and short half-life over a range of IV doses. It is rapidly and completely absorbed following IM or SQ administration.
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  • 109
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    European journal of clinical pharmacology 30 (1986), S. 113-120 
    ISSN: 1432-1041
    Keywords: theophylline ; pharmacokinetics ; stable isotopes ; diurnal variation ; single dose administration ; multiple dose administration ; systemic availability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline, enriched with the stable isotopes13C and15N, was administered intravenously in a dose of 10 mg to 8 healthy men following single (200 mg) and multiple (200 mg 8-hourly for 5 days) oral dose administration of aminophylline. Total plasma clearance, volume of distribution, and half-time determined from the intravenous data were similar, demonstrating that the pharmacokinetics of theophylline after chronic dosing can be predicted from the pharmacokinetics of a single dose. With chronic oral dosing, however, the mean trough concentration was 12% higher at 9 a.m. than at 5 p.m., the end of the dose interval (3.94±0.55 vs. 3.50±0.45 µg·ml−1). The AUC following oral dosing was 25% higher in the multiple dose study than in the single dose study. Simulation analysis suggested that these results could be explained by diurnal variation in the clearance or absorption rate or a combination of both. Thus, the systemic availability of theophylline measured during a single dosage interval after chronic oral dosing to steady state would be overestimated in comparison with that measured after a single oral dose.
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  • 110
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    European journal of clinical pharmacology 30 (1986), S. 127-129 
    ISSN: 1432-1041
    Keywords: oxazepam ; acetaminophen clearance ; metabolite formation ; glucuronidation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolism of acetaminophen and oxazepam in humans is mainly dependent on the microsomal capacity for glucuronide conjugation. The clearance of acetaminophen and the formation of metabolites were evaluated in 7 patients before and during concomitant administration of oxazepam 30 mg. The subjects received a single 500 mg dose of acetaminophen i.v. and concentrations in plasma were measured for 360 minutes and in urine for 24 h in order to estimate the production of metabolites. The single therapeutic dose of oxazepam had no effect on the clearance of acetaminophen or on formation of its metabolites.
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  • 111
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    European journal of clinical pharmacology 30 (1986), S. 133-139 
    ISSN: 1432-1041
    Keywords: felodipine ; hydrochlorothiazide ; essential hypertension ; calcium antagonist ; pharmacokinetics ; plasma noradrenaline ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind cross-over study, the effect on blood pressure (BP), heart rate (HR) and plasma noradrenaline concentration (pNA) of placebo or felodipine given in addition to hydrochlorothiazide was studied in 12 male patients with essential hypertension, not satisfactorily controlled with the diuretic alone. The first dose of felodipine decreased BP and increased HR for about 6 h. After 4 weeks of treatment with felodipine, BP was reduced for 24 h, whereas HR was only transiently increased. The elimination half-life of felodipine was about 23 h. The plasma noradrenaline concentration increased after felodipine and serum uric acid decreased. Side-effects were few and usually mild.
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  • 112
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    European journal of clinical pharmacology 31 (1986), S. 165-168 
    ISSN: 1432-1041
    Keywords: bromerguride ; dopamine antagonist ; pharmacokinetics ; pharmacodynamics ; prolactin level ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels and urinary excretion of the dopamine antagonist, bromerguride, were measured by radioimmunoassay in healthy male volunteers given 50 µg i.v. and oral doses of 1 and 2 mg. Plasma prolactin was also measured by radioimmunoassay. Following i.v. injection, the concentration of bromerguride declined biphasically, with half-lives of 7 min and 1.2h. The total clearance was 32 ml·min−1·kg−1 and the apparent volume of distribution was 3.6 l/kg. The bioavailability of oral bromerguride was 29% after 1 mg and 25% after 2 mg. The drug was almost totally metabolized and less than 0.05% of the dose was excreted in urine in 24 h after oral administration. Plasma prolactin levels were increased in a dose-dependent manner for about 8 h. Side-effects were minimal, mainly being tiredness and headache in some of the volunteers.
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  • 113
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    European journal of clinical pharmacology 29 (1986), S. 697-701 
    ISSN: 1432-1041
    Keywords: tenoxicam ; renal insufficiency ; non-steroidal antiinflammatory agents ; protein binding ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tenoxicam after a single oral dose of 20 mg has been studied in 12 patients with various degrees of decreased renal function. Unchanged tenoxicam and its 5′OH-metabolite in plasma and urine were determined by HPLC. The mean areas under the plasma concentration-time curve (138±53 µg/ml·h) and terminal half-lives in patients with impaired renal function did not differ from values previously reported in normal volunteers, nor did the peak concentration of tenoxicam. The half-life of 5′OH-tenoxicam and unchanged tenoxicam where the same. The urinary excretion of 5′OH-tenoxicam fell with decreasing renal function. Thus no dosage adjustment should be necessary and the usual daily dose of tenoxicam may be administered once daily also to patients with renal failure.
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  • 114
    ISSN: 1432-1041
    Keywords: idazoxan ; pharmacokinetics ; alpha 2-adrenoceptor antagonist ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high performance liquid chromatographic method was developed for the quantitative determination of idazoxan in plasma. The assay was used to study the disposition of the drug after intravenous infusion and oral administration to five normal subjects. After i.v. administration the kinetics could be described by a two compartment model with a mean elimination half life of 4.20 h. The mean calculated volume of distribution during the elimination phase was 3.20 l/kg−1 and the mean plasma clearance was 824 ml min−1. After oral administration a lag period before onset of absorption was observed in all five volunteers, the plasma levels declining monoexponentially from the peak concentration with a mean elimination half life of 5.58 h. The absolute availability varied between 26% and 41% with a mean value of 34%. Invitro measurements produced a blood/plasma ratio of 1.3 for idazoxan.
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  • 115
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    European journal of clinical pharmacology 30 (1986), S. 745-747 
    ISSN: 1432-1041
    Keywords: temazepam ; pharmacokinetics ; geriatric patients ; benzodiazepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of temazepam 10 mg, as a solution in soft gelatin capsules, was given to 10 fasting geriatric in-patients (mean age 83 years) in a stable clinical condition. The mean peak plasma concentration was 306 ng/ml, with a median time of 0.75 h to peak concentration. Temazepam was eliminated from plasma in a biexponential manner, with a distribution phase (mean t1/2α=0.7 h) predominating for 3 h. The drug had a mean elimination half-life of 8.7 h. In a chronic study, in which temazepam 10 mg p.o. was given nightly to 13 patients, the plasma concentrations on Days 3, 5, 8, 12 and 15 were not significantly different from each other, showing rapid attainment of steady state levels and the lack of drug accumulation.
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  • 116
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    European journal of clinical pharmacology 31 (1986), S. 23-26 
    ISSN: 1432-1041
    Keywords: sulphasalazine ; Pentasa ; slow release preparation ; 5-aminosalicylic acid ; ileo-rectal anastomosis ; ulcerative colitis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 5-aminosalicylic acid (5-ASA) from sulphasalazine (SASP) and the slow-release 5-ASA preparation Pentasa was investigated in a cross-over study in 9 otherwise healthy patients with an ileo-rectal anastomosis. The 24-hour recoveries of the drugs were 90.5% and 84.7%, respectively. The median release of 5-ASA from SASP was 50% and from Pentasa 75%. Equal amounts of 5-ASA (18.0% vs 17.9%) were found in the faeces, and a significantly larger amount (4.4% vs 28.9%) of the metaboliteN-acetyl-5-aminosalicylic acid (ac-5-ASA) was found in faeces following Pentasa. A larger amount of 5-ASA was absorbed and subsequently excreted in the urine, mainly as the metabolite (2.5% vs 20.5%) from Pentasa. This confirms previous results in ileostomized patients treated with Pentasa. The present findings also demonstrate that bacterial azo-reduction of SASP in patients with ileorectal anastomosis may be an adequate way to deliver 5-ASA in this type of patient. Both treatments may be used in these patients during a flare up of ulcerative colitis, but randomized studies are needed.
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  • 117
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    European journal of clinical pharmacology 31 (1986), S. 69-72 
    ISSN: 1432-1041
    Keywords: quinidine ; sparteine ; pharmacokinetics ; drug oxidation ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thus, it is unlikely that quinidine metabolism is controlled by the sparteine/debrisoquine gene locus.
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  • 118
    ISSN: 1432-1041
    Keywords: ceftriaxone ; dialysis ; continous ambulatory peritoneal dialysis ; pharmacokinetics ; intraperitoneal administration ; intravenous administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of ceftriaxone was investigated in 8 patients without infection, who were receiving continuous ambulatory peritoneal dialysis (CAPD). Ceftriaxone 1 g was injected i.v. and 1 g was given intraperitoneally in the CAPD fluid during a 4-h dwell time. Ceftriaxone was assayed by HPLC. After intravenous administration, the kinetic parameters of ceftriaxone were: plasma t1/2, 12.3 h, total plasma clearance, 14.0 ml/min, volume of distribution at steady state 0.18 l/kg, and peritoneal clearance 0.59 ml/min. Over 72 hours only 5.5% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftriaxone rapidly appeared in serum; the absorption t1/2 was 1.1 h and the mean peak concentration was 38.8 µg/ml. The absorption of ceftriaxone from the peritoneal space was 39%. A single 1.0 g IP dose led to serum and dialysate concentrations of ceftriaxone above the minimum inhibitory concentration for susceptible pathogens for 24 hours.
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  • 119
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    European journal of clinical pharmacology 31 (1986), S. 1-7 
    ISSN: 1432-1041
    Keywords: torasemide ; diuretic activity ; pharmacokinetics ; healthy subjects ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Torasemide 40 mg/day p.o. was administered for 21 days to 8 healthy volunteers to investigate its pharmacodynamics, pharmacokinetics and safety on chronic administration. It induced a highly significant initial increase in 24-h urinary volume and 24-h excretion of sodium and chloride, but its affect diminished after the first days. On Days 0, 1, 10 and 21 the experiement was divided in 3 clearance phases, extending from 0 to 2 h, 2 to 6 h and 6 to 24 h after dosing. The fractional excretion of sodium, chloride, potassium, calcium, magnesium and inorganic phosphates peaked during the first 2 h and returned almost to the control value during the following two clearance phases. The phase-dependent changes were significant for all electrolytes, except for potassium and inorganic phosphate. Plasma electrolyte levels remained constant throughout the study, except for a small decrease in chloride and potassium and for an increase in calcium and magnesium. Fasting blood glucose and glucose tolerance test were unaffected. A small but significant decrease in LDL-cholesterol was observed on Day 10. Other plasma lipid components showed minor changes. Plasma uric acid levels were moderately increased. There was no significant change of the creatinine clearance. Body weight fell significantly (by about 2 kg) during the study. Tonal audiometry was normal before and after the study. There was no significant difference between the plasma levels of torasemide on Days 1, 10 and 21, nor between its elimination half-life on Days 1 and 21. Side-effects consisted mainly of fatigue and low-back pain on days of intense diuresis. There were no toxic symptoms. ECG recordings and blood pressure remained within normal limits.
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  • 120
    ISSN: 1573-8221
    Keywords: 1,4-benzodiazepines ; pharmacokinetics ; plasma/brain concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 121
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    Bulletin of experimental biology and medicine 101 (1986), S. 333-335 
    ISSN: 1573-8221
    Keywords: antioxidant ; 3-hydroxypyridines ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 122
    ISSN: 1573-8221
    Keywords: dalargin ; pharmacokinetics ; enkephalins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 123
    ISSN: 1573-8744
    Keywords: hepatic elimination ; hepatic clearance ; availability ; intrinsic clearance ; pharmacokinetics ; dispersion model ; well-stirred model ; tube model ; distributed model ; blood flow ; binding within blood ; hepatocellular enzyme activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The dispersion model of hepatic elimination is based on the distribution of residence times of blood elements within the liver. The model has two asymptotic solutions corresponding to the “wellstirred” model (complete mixing of blood elements) and the “parallel-tube” model (no variation in residence times of blood elements). The steady-state form of the dispersion model relevant to pharmacokinetic analysis is developed and explored with respect to changes in blood flow, in binding within blood, and in hepatocellular enzyme activity. Literature data are used to evaluate discrepancies among the predictions of the dispersion, well-stirred, and tube models. It is concluded that the dispersion model is consistent-with the data. The limitations of steady-state perfusion experiments to estimate the residence time distribution of blood elements within the liver are considered.
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  • 124
    ISSN: 1573-8744
    Keywords: disopyramide ; pharmacokinetics ; stereoisomers ; antiarrhythmic agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disopyramide, an antiarrhythmic agent, is marketed as a racemic mixture of two enantiomers. The racemic drug has unusual pharmacokinetic properties because of its concentration-dependent binding to plasma proteins in the therapeutic plasma concentration range. This study examined, in healthy subjects, the individual pharmacokinetic properties of both total and unbound d-and ldisopyramide in plasma after intravenous administration of each enantiomer separately (1.5mg/kg).Also investigated is the pharmacokinetics of total d-and l-disopyramide in plasma after intravenous administration of a pseudoracemate. Both d-and l-disopyramide are found to exhibit concentration-dependent binding to plasma proteins, with d-disopyramide being more avidly bound at lower concentrations. The stereoselective, concentration-dependent binding to plasma proteins resulted in distinct pharmacokinetic properties when the enantiomers were given together as the pseudoracemate. d-Disopyramide had a lower plasma clearance and renal clearance, a longer half-life, and a smaller apparent volume of distribution than l-disopyramide. However, when the enantiomers were administered separately, there were no differences in the clearance, renal clearance, and volume of distribution between enantiomers calculated from either total or unbound drug concentrations. The results reveal an important pharmacokinetic interaction between the enantiomers of disopyramide when given as a racemic mixture, which may be dose-dependent and is not apparent upon administration of the enantiomers separately.
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  • 125
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 365-379 
    ISSN: 1573-8744
    Keywords: disopyramide ; bioavailability ; protein binding ; nonlinear ; sustained release ; pharmacokinetics ; ultrafiltration ; immunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disopyramide has nonlinear protein binding and thus the relationship between the extent of its bioavailability and AUC,the area under the plasma concentration-time curve, is (1) nonlinear and (2) absorption rate-dependent. The unbound species follows linear pharmacokinetics. A solution of disopyramide, the innovator's product, and two generic formulations were found to be statistically indistinguishable in their bioavailability of disopyramide, whether comparison was based upon AUCor area under the plasma unbound concentration-time curve (AUCu).The AUCand AUCugave similar results because of truly similar bioavailability, coupled with sufficiently similar release rates, among the four preparations chosen for study. The concentration dependence of disopyramide protein binding and the time course of unbound plasma concentrations were fit by models which then allowed prediction of AUCunder various biopharmaceutical scenarios. Nonlinear binding of disopyramide to plasma proteins renders AUCan insensitive parameter for the discrimination of products with different extents of bioavailability; immediate release products allowing bioavailabilities of 75 or 125% relative to the solution can generate AUCs86 and 112%, respectively, of that from the solution. Nonlinear binding, furthermore, leads to a tendency for AUC tooverestimate the bioavailability of slower release products in single-dose studies; if AUCwere the index of bioavailability, products permitting the same bioavailability as the solution but releasing over 12 hr could appear to allow 114% relative bioavailability. Moreover, in some situations the bias arising from the insensitivity of AUCto product differences can be reinforced by the dependence of AUCon release rate; an apparent relative bioavailability of 80% can be achieved by a 12-hr release product allowing a true relative bioavailability of a mere 58%. While multiple-dose studies appear largely to avoid the tendency to overestimate low bioavailability in slow-release products, in these studies AUCappears to be even more insensitive in resolving discrepancies between products. Assay technology now available makes AUCua feasible and more reliable index of bioavailability than AUCwhen plasma protein binding of drugs is nonlinear.
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  • 126
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 357-364 
    ISSN: 1573-8744
    Keywords: 16-acetyi-gitoxin ; pengitoxin ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In six volunteers the pharmacokinetics of 16-acetyI-gitoxin (16AG, 0.5mg) administered intravenously (A1) and as an oral solution (A2) and of pengitoxin (PAG, 0.6 mg) administered intravenously (A3) was evaluated. In six volunteers the bioavailability of 16AG from two PAG tablet formulations (1.2 mg) (B2, B3) was measured by comparison with the absorption after administration of a pengitoxin solution (1.2mg) (B1). In both studies the test was performed using a crossover design. After a single i.v. injection of equimolar doses, 16AG and PAG showed similar mean kinetic parameters: t 1/2 =51.6hr (16AG) and 60.8 hr (PAG), CL=11.7ml min−1 (16AG) and 12.7ml min−1 (PAG), CLR=4.1 ml min−1 (16AG) and 4.2ml min−1 (PAG). The 16AG was absorbed from solution with a mean half-life of 0.2hr to an extent of 98.6%. The mean urinary excretion /Ae(0, 4)/ of 16AG amounted to 24.6% (A1), 20.8% (A2) and 28.1% (A3). On the basis of AUCvalues, the mean bioavailability of PAG from either tablet formulation amounted to 79.6% (B2) and 89.6% (B3). The pharmacokinetic parameters of 16AG (PAG) are closer to those of digitoxin than those of digoxin. In general, 16AG is characterized as a digitoxin with a digoxin-like elimination half-life.
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  • 127
    ISSN: 1573-8744
    Keywords: isosorbide dinitratekw]isosorbide 2-mononitrate ; isosorbide 5-mononitrate ; metabolism ; pharmacokinetics ; modeling ; simultaneous estimation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma concentrations of isosorbide dinitrate (ISDN) and its two active metabolites 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) have been measured during and for 6 hr after intravenous infusion at a rate of 2.5mg/hr during 1.75 hr in six cardiac patients, by a capillary gas chromatographic method. Data were analyzed by simultaneous modeling of the observed kinetics of the three compounds. Two or three phases were detected on the postinfusion ISDN concentration-time curves. ISDN concentrations declined with a mean terminal half-life of 2.81 hr±0.7 SD. The mean systemic clearance of ISDN (2.9 L/min ±0.7 SD) and its mean total volume of distribution (259 L +- 48 SD) were relatively high. Plasma 5-ISMN concentrations were 5- to 6-fold greater than those of 2-ISMN during the whole observation period. Maximum levels of 2-ISMN (6.7 ng/ml ± 0.9 SD) and of 5-ISMN (27 ng/ml ± 6 SD) occurred within a few minutes after the end of infusion. The mean half-lives of 2-ISMN (1.59 hr± 0.19 SD) and of 5-ISMN (3.78 hr± 0.79 SD) estimated by the model were smaller than those calculated by a model-independent method (2.95 hr± 0.41 SD and 5.98 hr± 2.22, respectively), but were in good agreement with those reported in the literature following separate administration of both metabolites to man. This study shows how such modeling can distinguish between metabolite formation and elimination processes and allow the determination of metabolite half-lives after administration of the precursor drug.
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  • 128
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 131-155 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; physiological model ; cisplatin ; DDP ; cis-dichlorodiammineplatinum(II)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiological pharmacokinetic analysis ofcis-dichlorodiammineplatinum(II) (DDP) is presented for the rabbit, dog, and human. The results are compared to a previous analysis for the rat. DDP binds irreversibly to low-molecular weight nucleophiles and macromolecules to form mobile and fixed metabolites at rates which are tissue-specific. The rate constant for the formation of fixed metabolite in plasma, determined by in vitro incubation, ranges from 0.004 to 0.008 min−1.
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  • 129
    ISSN: 1573-8744
    Keywords: camazepam ; temazepam ; oxazepam ; pharmacokinetics ; anticonvulsant effect ; radioreceptor assay ; rat ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In a displacement test using3H-diazepam as a radioligand, the in vitro affinities of metabolites of camazepam (CZ) for the benzodiazepine receptors were 1–50 times more potent than that of CZ. In contrast, only three metabolites (temazepam, oxazepam, and hydroxy CZ), as well as CZ itself, exhibited an in vivo affinity parallel to their ability to protect against pentylenetetrazole-induced clonic convulsion in rats. In addition, CZ and these active metabolites displaced the radioligand from their receptor sites in a concentration-dependent saturable manner, indicating the competitive bimolecular interaction of these molecules with their receptors. The percent anticonvulsant effect was a nonlinear, single-valued function of the in vivo percent displacement of specific3H-diazepam binding, independent of these displacers after i.v. dosing; this relationship could be approximated by the Hill equation. On the basis of these findings, a receptor-mediated model, including the Langmuir equation to describe the receptor binding-brain concentration relationship and the Hill equation to accommodate the anticonvulsant effect-receptor binding relationship, was constructed. This model was found to adequately relate the time course values of anticonvulsant effect and of brain levels of CZ and its active metabolites after oral administration. These results demonstrate that CZ and its active metabolites exert anticonvulsant effect by competitive binding to the benzodiazepine receptors.
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  • 130
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 397-408 
    ISSN: 1573-8744
    Keywords: caffeine ; ceftriaxone ; plasma ; tissue ; pharmacokinetics ; compartment model ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Previous studies have shown that caffeine can affect drug kinetics by altering drug binding to plasma protein, drug absorption, or drug distribution. In this study, the effect of caffeine on the in vivoprotein binding and the disposition of ceftriaxone (a highly protein-bound cephalosporin) were investigated in the rat. Ceftriaxone 100mg/kg and caffeine 20mg/kg were i.v. injected via the tail vein and ceftriaxone in plasma, plasma filtrate, urine, feces, and tissues (brain, heart, kidney, liver, gut, lung, and muscle) was assayed by HPLC with UV detection. The fraction of free ceftriaxone in plasma ranged from 5.6 to 32.8% of total ceftriaxone (3–347 μg/ml) without caffeine and showed no alteration by caffeine. The total amount of ceftriaxone excreted in urine and feces was increased significantly (p〈0.05)from 13.1±1.8mg (mean±SD, 54.6% of total) to 15.3 ±1.1 mg (63.8% of total) by caffeine coadministration. The terminal half-life of ceftriaxone in plasma was shortened from 59 to 47 min, and the area under the plasma drug concentration-time curve (AUC)was reduced from 612 to 516 μg hr/ml Although the peak drug concentrations and the times of peak concentration of ceftriaxone in tissues were not altered by caffeine administration, the elimination of ceftriaxone was increased, as indicated by generally shorter half-lives (decreases ranged from 17.5% in liver to 34.2% in brain) and lower AUCvalues (from 9.0% in heart to 54.5% in brain). These results suggest that caffeine does not alter the protein binding of ceftriaxone, but enhances the elimination of ceftriaxone in the rat.
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  • 131
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 29-49 
    ISSN: 1573-8744
    Keywords: carbon dioxide ; breath test ; pharmacokinetics ; metabolite ; extraction ratio ; aminopyrine ; caffeine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The interrelationship of the pharmacokinetics of a drug and the expiration of carbon dioxide formed as a metabolite have been studied. The pharmacokinetic characteristics of the drug that affect the usefulness of the carbon dioxide excretion as a measure of liver function were examined by means of computer simulations. The parent drug extraction ratio, fraction demethylated, volume of distribution, and absorption rate of an oral dosage form all contribute to the carbon dioxide breath test result. A drug that would be a useful substrate when the carbon dioxide breath test is used as a probe for changes in liver function should be at least 50% metabolized by demethylation, have a hepatic extraction ratio of 0.2–0.5, and be administered in a form that is rapidly absorbed.
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  • 132
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 495-509 
    ISSN: 1573-8744
    Keywords: furosemide ; pharmacokinetics ; pharmacodynamics ; fluid replacement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments. Renal clearances and urinary excretion rates of the drug in treatments II–IVwere essentially the same, but about 20% higher than those in treatment I.In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were markedly different among the four treatments. For example, mean 10-hr urine outputs were 646, 1046, 3156, and 1976 ml and mean 10-hr sodium excretions were 87.0, 142, 383, and 97.2 mmole for treatments I–IV,respectively. Except for treatment III,diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (1)no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (2)in treatment II,where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition; (3)at steady state the hourly diuresis and natriuresis could differ up to about ten times between treatments. Some implications for the kinetic/dynamic relationship or modeling, in the clinical use, and in the bioequivalence evaluation of dosage forms are discussed.
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  • 133
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 601-613 
    ISSN: 1573-8744
    Keywords: amiodarone ; pharmacokinetics ; dose-dependent ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Single intravenous bolus doses of amiodarone hydrochloride of 30, 60, 90 and 120 mg/kg were administered to male Sprague-Dawley rats to determine the effects of dose on amiodarone pharmacokinetics. Serial blood samples and total urine were collected over 48 hr and assayed for amiodarone and desethylamiodarone by HPLC. The blood amiodarone concentration-time curves for the four doses were best described by a triexponential equation with terminal half-lives (t 1/2γ ) ranging from 17 to 20 hr. Over the dose range studied, no changes in γ, t 1/2γ , or central compartment volume (Vc=1.2–1.4 L/kg) were observed. On the other hand, reductions in amiodarone clearance (CL and steady-state volume of distribution (V ss of 44% (17.7 to 10.0 ml/min per kg) and 50% (16.4 to 8.2 L/kg), respectively, were noted as the dose of amiodarone increased. The conversion of amiodarone to desethylamiodarone (fm was dose-independent and amounted to approximately 10% of each amiodarone dose. No amiodarone or desethylamiodarone was detected in the urine of any of the treated animals. The blood-to-plasma concentration ratio of amiodarone was concentration-independent and therefore did not account for the dose-dependent changes in Vss and CL observed. The data suggested that the dose-dependent changes noted were due to an alteration in the volume (s) of the peripheral tissue compartment(s).
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  • 134
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    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 381-395 
    ISSN: 1573-8744
    Keywords: pethidine ; rat ; physiological flow model ; pharmacokinetics ; pregnancy ; scale up ; opiates, GC-MS analytical method ; simulations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The disposition of pethidine (meperidine) in the pregnant rat is described by means of a physiological flow model. The model includes arterial and venous blood, brain, fat, fetal, hepatic, intestinal, muscular, pulmonar, and renal tissues. The concentration-time profiles of pethidine calculated by the model are consistent with experimental data, except for the brain and renal tissues, where the model predicts initially higher concentrations. Simulations are carried out to further explore the contribution from different organs on the kinetics in blood and tissues. The tissue-to-blood partition coefficients vary over a range from 5 to 316, where fat has the lowest and liver the highest after a correction is made due to hepatic extraction. Rapid uptake occurs into highly perfused organs such as brain, kidneys, liver, and lungs, followed by fetus, intestines, muscle, and fat. Data indicate no marked membrane resistance to pethidine of the investigated organs, except for fetal tissues, but rather a perfusion-limited uptake. Simulations suggest that muscles and adipose tissue play an important role in the rat, becoming the major reservoir of drug during the intermediate and terminal elimination phase, respectively. Volume of distribution and the biological half-life agree with reported findings. Pethidine is subject to a high systemic blood clearance, which exceeds the total hepatic blood flow in the rat. No degradation of pethidine is found in blood, and therefore a pulmonary expression for pethidine clearance is added as a potential source of pethidine elimination. The elimination of pethidine after a single i.v. bolus dose is found to be dependent on simulated changes in cardiac output and hepatic blood flow. A simulation is performed with the scaled model to mimic the human concentration-time profiles in maternal blood and brain tissues and fetal tissue during repetitive doses of pethidine.
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  • 135
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    Pharmaceutical research 3 (1986), S. 150-155 
    ISSN: 1573-904X
    Keywords: renal clearance ; cephalosporin ; cefixime ; tubular reabsorption ; saturable protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of cefixime, a new orally active cephalosporin, was studied after an intravenous dose of 50 mg/kg to four beagle dogs. Cefixime was shown to exhibit concentration dependent serum protein binding and saturable tubular reabsorption. The drug was excreted mainly in the urine, the net result of glomerular filtration and saturable tubular reabsorption. The experimental results were analyzed by model independent pharmacokinetic equations and with theoretical models describing renal clearance. Modification of the models, based on observed data, was proposed. The experimental methods employed and the pharmacokinetic approach offered in this study can be applied to drugs that exhibit concentration dependent protein binding and saturable renal elimination processes.
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  • 136
    ISSN: 1573-904X
    Keywords: amiodarone ; theophylline ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Amiodarone is an investigational antiarrhythmic agent which has been implicated in reducing the activity of the hepatic mixed-function oxidase system. To evaluate this effect further, two groups of six male Sprague–Dawley rats each received theophylline (6 mg/kg, iv) preceded by either normal saline or amiodarone HC1 (100 mg/kg, iv). Blood samples were obtained serially for a period of 6 hr and the sera were assayed for theophylline by high-pressure liquid chromatography (HPLC). In rats pretreated with amiodarone, a significant 45% reduction in the mean (± SD) systemic clearance [0.057 (0.010) vs 0.031 (0.004) liter/hr/kg, P 〈 0.001] and a greater than 100% increase in the mean elimination half-life [2.03 (0.46) vs 4.29 (0.71) hr, P 〈 0.001] of theophylline were observed. These data demonstrate an acute inhibitory effect of amiodarone on the hepatic microsomal enzyme system.
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  • 137
    ISSN: 1573-904X
    Keywords: drug delivery, targeted ; prodrugs ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiologically based model is presented to aid prediction of the pharmacological benefits to be derived from the administration of a drug as a targeted drug–carrier combination. An improvement in the therapeutic index and an increase in the therapeutic availability are the primary benefits sought. A measure of the former is obtained from the value of the drug targeting index, a newly derived parameter. Both the drug targeting index and the therapeutic availability are directly calculable. The minimum information needed for approximating both parameters is the candidate drug's total-body clearance and some knowledge of the target site's anatomy and blood flow. Drugs with high total-body clearance values that are known to act at target tissues having effective blood flows that are small relative to the blood flow to the normal eliminating organs will benefit most from combination with an efficient, targeted carrier. Direct elimination of the drug at the target site or at the tissue where toxicity originates dramatically improves the drug targeting index value. The fraction of drug actually released from the carrier at both target and nontarget sites can radically affect index values. In some cases a 1% change in the fraction of the dose delivered to the target can result in a 50% change in the drug targeting index value. It is argued that most drugs already developed have a low potential to benefit from combination with a drug carrier. The approach allows one to distinguish clearly those drugs that can benefit from combination with targeted in vivo drug carriers from those drugs that cannot.
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  • 138
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    Pharmaceutical research 3 (1986), S. 352-355 
    ISSN: 1573-904X
    Keywords: malnutrition ; metronidazole ; pharmacokinetics ; rats ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The influence of dietary protein deficiency on the disposition of metronidazole and its two major metabolites was examined in male Sprague–Dawley rats fed for 4 weeks on a 23% (control-) or a 5% (low-) protein diet ad libitum. Following an intravenous bolus dose of 10 mg/kg metronidazole hydrochloride, blood samples were obtained serially for a period of 24 hr after drug administration. Serum concentration–time data were analyzed by nonlinear least-squares regression, as well as noncompartmental techniques. The average mean residence time (MRT) was significantly prolonged by 48%, while the systemic clearance (Cl) was decreased by 42% in the protein-deficient rats. Since there was no alteration in the apparent steady-state volume of distribution (V ss), the mean harmonic half-life was increased from 2.9 to 5.0 hr in the protein-deficient rats. Although the percentage of metronidazole recovered as total drug in the urine over 24 hr was not significantly different between the two groups of animals, rats on a low-protein diet excreted a significantly smaller percentage of the administered dose as unchanged metronidazole (mean ± SD, 24.6 ± 3.8 vs 36.5 ± 12%) and a larger percentage (16.7 ± 2.6 vs 8.3 ± 1.8%) as the hydroxylated metabolite. No significant difference in the partial metabolic clearance of the hydroxylated metabolite of metronidazole was seen between the two groups of animals; however, there was a significant decrease in the renal clearance of metronidazole (1.45 ± 0.68 vs 0.55 ± 0.06 ml/min/kg) in the rats fed a low-protein diet. We conclude that the decreased clearance of metronidazole in protein deficiency is a result primarily of the decreased glomerular filtration rate, decreased biliary excretion, and/or increased net tubular reabsorption of metronidazole.
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  • 139
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    Pharmaceutical research 3 (1986), S. 108-111 
    ISSN: 1573-904X
    Keywords: propranolol ; intranasal ; sublingual ; absorption ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of propranolol was compared after oral, sublingual, and intranasal administration in eight healthy male volunteers. Relative to the bioavailability after intranasal (in) administration, which was previously shown to be nearly complete (F relin = 100%), the sublingual (sl) administration of a standard 10-mg tablet gave a bioavailability of F relsl = 63 ± 22%, while the oral (or) administration yielded only F relor = 25 ± 8%. The serum concentration–time curves of propranolol after sublingual administration resembled those of a sustained-release preparation. This sustained-release phenomenon after the sublingual route is reflected in the mean residence times (MRTs) of propranolol in the body (MRTor = 5.7 ± 1.3 hr, MRTsl - 6.4 ± 1.3 hr, MRTin = 4.6 ± 1.0 hr; mean ± SD; N = 8). MRTs after sublingual administration were significantly longer than after the oral and the intranasal doses (P 〈 0.05 and P 〈 0.002, respectively).
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  • 140
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    Pharmaceutical research 3 (1986), S. 173-177 
    ISSN: 1573-904X
    Keywords: sulfinpyrazone ; pharmacokinetics ; reversible metabolism ; single dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In rabbits receiving sulfmpyrazone (SO) and the sulfide metabolite (S) in four separate experiments, the biotransformation of SO into S was found to be reversible, which resulted in approximately parallel terminal disposition profiles for the three major substances in plasma, i.e., SO, S, and the p-OH-sulfide (OH-S). However, differences in disposition kinetics were observed between the intravenous and the peroral administration. The formation of OH-S was independent of both the administered compound and the administration route. The results obtained in the present studies, the previously documented enterohepatic recirculation, and the formation of S by hindgut flora may have implications for studies on sulfinpyrazone, which has been used as an antithrombotic agent.
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  • 141
    ISSN: 1573-904X
    Keywords: sulfinpyrazone ; pharmacokinetics ; reversible metabolism ; multiple dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In crossover studies rabbits were given sulfmpyrazone (SO) and its sulfide metabolite (S) perorally once daily (10 mg/kg) for 5 days. Comparison of the pharmacokinetic parameters obtained after the first and the fifth dose indicates that repeated dosing does not alter disposition kinetics of both SO and S, except that in dosing with S the observed terminal half-life for S is significantly reduced, from 4.59 ± 0.55 to 2.86 ± 0.6 hr (SD). In other studies rabbits were given higher single doses (15, 25, and 50 mg/kg) perorally and comparison was made between these dose sizes and the first dose (10 mg/kg) of multiple administration with S. Some kinetic parameters tended to be altered in a nonlinear fashion, and greater intersubject variations were observed because of the dose increase, while oxidation to SO or p-hydroxylation to OH-S from S was not significantly altered.
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  • 142
    ISSN: 1573-7217
    Keywords: medroxyprogesterone acetate ; pharmacokinetics ; response ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 143
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    Journal of Morphology 187 (1986), S. 159-172 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Teleost enameloid matrix has been proposed to be an ectodermal, mesodermal, or joint ectodermal-mesodermal product. To determine its origin we examined the ultrastructure of the inner dental epithelium (IDE), odontoblasts, enameloid, and dentin matrices of cichlid tooth buds at the stage of enameloid formation. © Alan R. Liss, Inc.Columnar IDE cells had apical and basal terminal webs and contained organelles associated with protein synthesis, including elongated secretory granules containing fibrillar material having cross-striations with 60-nm periodicity. The morphology of IDE secretory granules was typical of procollagen granules observed in a large variety of ectodermal and mesodermal cells synthesizing collagen. In contrast, the paucity of secretory granules within three odontoblast types indicates that these cells probably do not synthesize enameloid matrix. These observations are consistent with the idea that the bulk of the enameloid matrix is itself an ectodermal collagen synthesized and secreted by IDE cells.
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  • 144
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    Journal of Morphology 187 (1986), S. 181-199 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology and fine structure of the basilar recess and basilar papilla were investigated in four species of salamanders from the family Ambystomatidae. The otic relationships of the recess and papilla to the proximal part of the lagena and saccule are described, and new terminology is suggested for the periotic relationships of the basilar recess to a diverticulum of an intracapsular periotic sac. The basilar papilla consists of supporting cells united laterally by gap junctions, capped by microvilli uniformly arranged around a short, central cilium, and hair cells that typically show several synapses with a single afferent nerve fiber, each marked by a rounded synaptic body surrounded by vesicles. In contrast to anuran basilar papillae, efferent nerve terminals were observed in synapse with hair cells and, rarely, upon afferent fibers. The distal half of the ambystomatid papilla contained hair cells capped by tall ciliary bundles, with kinocilia that show swellings near their tips with delicate attachments to adjacent tall stereocilia. A tectorial body covers only this region of the papilla. Hair cells with shorter stereocilia, situated in the proximal half and at the papillar margins, are related only to filamentous extensions of the tectorial body. The ambystomatid basilar recess and papilla are compared to auditory end-organs in other vertebrates, and it is suggested that a basic distinction can be made between aural neuroepithelia in amniotes versus that in nonamniotic vertebrate ears.
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    Journal of Morphology 187 (1986), S. 247-258 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Length-force relations, both active and passive, and twitch contraction characteristics were quantified for left medial gastrocnemius muscles of four young, four adult, and four old male Wistar rats. Muscle and bundle optimum length and muscle weight were also determined and subsequently used for calculation of a number of morphological characteristics of the muscles. Fiber optimum length was derived from muscle bundle optimum length. Generally, physiological characteristics remained constant during growth. There was no change either in active tension at muscle optimum length or in active working range relative to fiber optimum length, relative passive fiber stiffness, active force relative to passive force at optimum length, twitch contraction time and twitch half relaxation time at optimum length. A number of morphological changes, however, did take place in the medial gastrocnemius muscle during growth. Fiber optimum length increased but only by about 2 mm from youth to old age, whereas muscle optimum length increased by approximately 14 mm, presumably owing to extensive hypertrophy of the muscle fibers during growth. The priority for force of the medial gastrocnemius muscle (defined as the quotient of physiological cross-sectional area of a muscle and the cubed root of its volume, a measure independent of architecture and dimensions of muscles) increased during growth. This increase indicates that during growth the muscle shifts relatively more towards force generation than towards excursion generation. These findings are discussed in view of existing scaling theories.
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  • 146
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    Journal of Morphology 188 (1986) 
    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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  • 147
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    Journal of Morphology 187 (1986), S. 363-386 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: An atlas of the brain of the horseshoe crab Limulus polyphemus is developed. All of the neuronal groups are identified and named, and regions of neuropil are segregated and named where possible. The nomenclature incorporates functionally neutral earlier names and assigns geographical names to newly distinguished structures. The atlas provides a basis for correlating the results of neuroanatomical, neurophysiological, and neurochemical studies, which yield information about individual neurons or groups of neurons in this species
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  • 148
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    Journal of Morphology 188 (1986), S. 1-13 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In addition to the supralabial glands (strips of glandular tissue lying along the maxilla), most snakes of the family Colubridae possess an enlarged oral gland lying behind the eye and emptying near the rear maxillary teeth, the Duvernoy's gland. Duvernoy's gland is most probably homologous to the venom gland of viperid and elapid snakes, and occasionally has been implicated in cases of human envenomation. Although of possible medical concern, there is reason to believe that secretion from this gland serves a biological role different from that of the venom gland, namely a role primarily in digestion rather then largely in rapid prey immobilization. The parenchyma of the Duvernoy's gland comprise two cell types, a serous cell containing numerous, electron-dense secretory granules, and myoepithelial cells. There are no mucous cells in the parenchyma; instead cells of this type are located exclusively in the lining epithelium of the main duct. Numerous unmyelinated nerves pass between secretory acini. Observations of the supralabial gland reveal that this gland, in addition to serous cells, also contains mucous cells and a putative third cell type we designate as an intermediate cell.In cellular morphology, Duvernoy's gland is closest to the venom gland of elapids, and least like the venom gland of viperids. Compared to the venom glands in both families of venomous snakes, Duvernoy's gland lacks a large luminal secretory reservoir. Emptying of Duvernoy's gland is thought to involve release of secretion granules into the lumen, and movement of the secretory product from there may be supplemented by mechanical pressure exerted externally by nearby contracting striated mucles. These differences in structure and mechanism of secretion release are taken as evidence that although they are homologous, the two types of glands, Duvernoy's and venom glands, are functionally distinct.
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  • 149
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    Journal of Morphology 188 (1986), S. 69-78 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Regional differences of the surface of planarian gastrodermal cells are emphasized by staining with ruthenium red (RR). It is proposed that such differences reflect functional diversity of the luminal, lateral, and basal surfaces of the cells. The luminal surface is coated with a uniform layer of the RR-positive substance, which penetrates into the intercellular space at the intermediate junction. The septate junction situated just beneath the intermediate junction shows a permeability barrier to the RR tracer. At the basolateral surface, however, RR stains the septate junction in which the electron density of individual septa is enhanced remarkably. The gastrodermal cells are delineated entirely with RR-positive substance passing freely through the gap junction fuses into the outer leaflets of adjacent plasma membranes. The irregularly dilated intercellular space at nonjunctional appositions includes a slight deposit of RR-positive substance which attaches to the plasma membrane. The basal surface is underlined by the continuous basal lamina, which consists of the lamina lucida and the lamina densa. The lamina densa has a conspicuous affinity for RR. The lamina lucida is characterized by irregular deposits of RR-positive substance, some of which concentrates on the hemidesmosomal portions. Treatment with the enzyme hyaluronidase prior to staining with RR abolishes the staining of the basal lamina. As a result, the material of the lamina densa appears flocculent.
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  • 150
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    Journal of Morphology 188 (1986) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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  • 151
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    Journal of Morphology 188 (1986), S. 129-156 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology and histology of the tongue in Sphenodon punctatus are described and used to infer function and to determine character state polarities in lepidosaurs. The tongue lacks an anterior notch and is covered with filamentous papillae, including specialized gustatory papillae containing taste buds. Lingual glands are restricted to mucocytes covering the papillae. Three intrinsic tongue muscles are identified and shown to be discrete fiber systems and not merely elaborations of the M. hyoglossus. These muscles interact with a connective tissue skeleton, particularly three septal planes, to cause changes in tongue shape. Tongue protrusion is probably caused by hyoid protraction and contraction of posterior genioglossus fibers; retraction by hyoid retraction, hyoglossus contraction, and contraction of anterior genioglossus fibers.It is argued that taste is important in prey discrimination and possibly in courtship. Vomeronasal function is probably mediated by inhalation and not tongue movement.Insertion of genioglossus fibers into the buccal floor is a derived feature of lepidosaur tongues. Derived features of squamate tongues include an anterior bifurcation, a divided genioglossus comprising medial and lateral portions, ventral transverse and circular muscle fiber systems around the hyoglossus, and the presence of a median septum. The tongue of the squamate family Iguanidae shares many plesiomorphic features with Sphenodon.
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  • 152
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    Journal of Morphology 188 (1986), S. 191-201 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The epithelium of the ileum of Locusta migratoria is composed of a single layer of columnar cells surrounded on the luminal side by cuticle and on the haemocoel side by a circular muscle layer. Where the circular muscles contact the epithelium, longitudinal muscles are present and the epithelium is slightly reduced. Elsewhere, a subepithelial sinus separates the epithelium from the circular muscle layer. The epithelial cells are characterised by extensive infoldings of the apical and basal cell membranes, which in the latter case, produce a maze of interconnecting channels and spaces. Mitochondria are closely associated with both apical and basal infoldings, although the bulk of these organelles is located in the cytoplasm underlying the infoldings of the apical plasma membrane. Vesicles of assorted sizes occur throughout the cytoplasm. They are particularly abundant in the apical region, where they appear to be produced by pinocytosis. Larger vesicles, containing either material of varying electron density or smaller vesicles, occur in the medial and basal regions of the cells. The contents of some of these vesicles have, in section, a lamellar appearance, composed of concentric layers of material. Similar vesicles are present in the basement membrane as well as the cells and connective tissue of the subepithelial sinus. Microtubules and groups of ribosomes commonly occur throughout the cytoplasm, and lipid-like droplets are also present in some of the cells. Ultrastructural features of the epithelial cells are discussed in relation to current knowledge of the function of the ileum.
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  • 153
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    Journal of Morphology 188 (1986), S. 29-37 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This work is concerned with the ultrastructural organization and some histochemical features of the vacuolar cells of the demosponge Oscarella lobularis. Vacuolar cells are characterized by large clear vacuoles containing an aqueous fluid. They are commonly found in the mesohyl of this sponge and tend to constitute a sort of parenchyma in the choanosome. Mobile cells of the mesohyl appear to differetiate into vacuolar cells through the progressive formation of wide cytoplasmic lacunae. We have identified four types of cells showing progressive transformation toward the vacuolar cell type. Precursors (types 1-4) of the vacuolar cells probably derive from endopinacocytes, since they share several histochemical and ultrastructural characteristics with them. Our data support the notion that vacuolar cells are involved in the synthesis of collagen, act as a mechanical support of the sponge body, and are eventually extruded from the sponge through the canals of the aquiferous system.
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  • 154
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    Journal of Morphology 188 (1986), S. 51-67 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The innervation of the mandibular nerve of the worker honey bee was investigated primarily with methylene blue vital staining. Results on the motor innervation were compared with those of earlier work, yielding some corrections and new findings. The nerve to the mandibular abductor muscle not only carries motor fibers but also supplies sensory branches to the head integument and to the presumptive proprioceptors which probably monitor movements of the proboscis. A small neural mass which is equipped with two systems for proprioception is situated at the point where the mandibular nerve divides into its major branches. One system is composed of receptor muscles stretched between the anterior tentorial arm (AT) and the mandible and multipolar cells. The other is composed of elastic strands between AT and the apodeme of a smaller branch of the mandibular adductor and tripolar cells. The former is stretched by mandibular abduction and the latter by adduction. The two systems collectively are called the mandibular muscle receptor organ. There are two groups of receptor muscles: the outer receptor muscle, which is located outside the neural mass, and the inner receptor muscle located within. Only the latter is innervated by multipolar cells. Another, single, multipolar cell is attached to the surface of the tendon of the inner receptor muscle. A further pair of bipolar-multiterminal cells attaches to the epidermis at the extremity of the apodeme of the mandibular adductor. One originates from the mandibular nerve and the other from the labral nerve. Both presumably respond to the epidermal expansion caused by mandibular abduction.
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  • 155
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    Journal of Morphology 188 (1986), S. 157-165 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A tympanohyal bone is reported in dolphins for the first time. The exceptional occurrence of this element in the bottlenose dolphin (Tursiops truncatus) and its location in a furrow of the tympanic can be taken as a vestige of an ancestral conformation indicating that, in cetacean ancestry, uncoupling of the periotic from the mastoid must have taken place laterally and dorsally to attachment of the hyoid arch and the stylomastoid foramen. There is a good correspondence between morphology and topographical relations of structures surrounding the facial canal in toothed whales and terres-trial mammals (especially perissodactyls and artiodactyls).During early cetacean evolution, the tympanic had to undergo strong modification because of its functional correlation with the periotic. In precetaceans, the tympanic was probably loosely attached to neighboring skull bones, while at the same time it was suspended from the periotic via the tympanohyal. The earliest known cetaceans obviously lost this indirect osseous suspension but retained the peripheral attachments of the tympanic. In advanced archeocetes, two of these attachments are maintained but have shifted onto the periotic. In modern dolphins, the tympanic is in firm osseous contact exclusively with the periotic (tympano-periotic complex). Both elements are isolated from the skull acoustically and form a separate mechanical unit specialized for high-frequency underwater sound perception.
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  • 156
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    Journal of Morphology 188 (1986), S. 179-189 
    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 morula cells of Eupentacta quinquesemita and the distribution of these cells in the dermal connective tissue are described. Morula cells are abundant in the dermis and appear to function in the maintenance of the extracellular matrix (ECM) as a source of ground substance material. The synthetic activity of these cells is described in detail. Morula cells are filled with large secretory vesicles containing three electrondense materials which are derived from rough endoplasmic reticulum and Golgi activity. The synthetic product of these cells contains glycosaminoglycans and is secreted into the ECM by degranulation. The ultrastructural and histochemical similarity of the degranulation product to the ECM ground substance suggests that they are comprised of the same material. Morula cells appear to function primarily in connective tissues where ground substance predominates. The cells often contain secretory vesicles at various stages of formation, all of which eventually mature and degranulate. The synthetic pathway of the morula cells appears to result ultimately in the complete disruption and death of the cells. The function of morula cells in the holothuroid ECM is discussed, and the synthetic activity of the cells is compared with that of other secretory cells.
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  • 157
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  • 158
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    Journal of Morphology 188 (1986), S. 239-250 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Early events during mouth formation in embryos of the starfish Pisaster ochraceus have been studied with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Embryos examined by TEM were fixed in glutaraldehyde with Alcian blue, a dye which preserves extracellular materials. Initially, mesenchyme cells migrate off the tip of the archenteron, leaving a defect in the cell layer that is covered by the basal lamina. This region of “naked” basal lamina bulges into the blastocoele and forms a hemispherical blister. At the same time that this is occurring, filamentous and conical processes extend from the inner surface of the presumptive stomodeal ectoderm cells which are located directly opposite the bulge of basal lamina. These processes penetrate the ectodermal basal lamina and project “naked” plasmalemma into the blastocoele. Shortly after this, the blister of endodermal basal lamina becomes irregular in shape, and scattered cells are found both within the blister and between it and the presumptive stomodeal ectoderm cells. Processes of endodermal cells appear to make contact with the filamentous processes of the stomodeal ectoderm cells. In other embryos which appear to be at a slightly later stage, the free basal lamina is conical in shape and is associated with at least one conical ectodermal process. In yet other embryos, the free endodermal basal lamina is either in contact with several other large processes forming a circular region of contact, or the free endodermal and ectodermal basal laminae are fused at the edge of the circle. Degeneration of both the ectodermal and endodermal basal laminae located within the circle, and subsequent invagination of the stomodeal ectoderm, appear to complete this process. The pulsations of stomodeal ectodermal cells seen throughout early stages in mouth formation may be involved in these events.
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  • 159
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    Journal of Morphology 188 (1986), S. 327-333 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The vascularization of the distal accessory flexor muscle (DAFM) in the walking legs of the lobster, Homarus americanus, was examined with dye injection and electron microscopy. Vascularization of this flat, thin DAFM is via two vessels, one supplying the tendinal region of the muscle and the other the exoskeletal region. The vessels that originate from the single major limb vessel, subdivide extensively over the DAFM and form a profuse network that has hitherto gone unnoticed. The degree of vascularization of individual fibers was determined by periodic sampling along its length with thin-section electron microscopy. At each and every sampling station, individual fibers had several (seven to eight), small-diameter (4 μm) blood vessels in their cross-sectional profile. In contrast, nerve terminals of the excitor and inhibitor axon were rarely encountered. This high degree of vascularization was found amongst fibers that are from different regions of the DAFM and differ in the performance of their excitatory synapse but are similar in their structural and contractile properties.
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  • 160
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    Journal of Morphology 189 (1986), S. 199-213 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The secondary palate of mammals is a bony shelf that closes the ventral aspect of the rostrum. The rostrum, therefore, approximates to a tapered semicylindrical tube that is theoretically a mechanically efficient structure for resisting the forces of biting, including the more prolonged bouts of mastication typical of mammals. Certain mammal-like reptiles illustrate stages in the development of the palate in which the shelves projecting medially from each premaxilla and maxilla do not meet in the midline. We evaluate several geometric properties of sections through the rostrum of the American opossum (Didelphis virginiana). For loading at the incisors and canines, these properties indicate the structural strength and stiffness in both bending and torsion of the rostrum and of single maxillae. We then repeat the analysis but progressively omit segments of the palatal shelf, a procedure which simulates, in reverse, the evolutionary development of the structure. The results demonstrate that the secondary palate contributes significantly to the torsional strength and stiffness of the rostrum of Didelphis and to the strength of each maxilla in lateromedial bending. The major evolutionary implications of the results are that the rapid increase in rostral strength with small increments of the palatal shelves may have been a significant factor in the development of the complete structure. The results indicate that there was a marked jump in torsional strength and stiffness when the shelves met in the midline, which is likely to have been important in the subsequent development of the diverse masticatory mechanisms of cynodonts and mammals. On the basis of this analysis the mammalian secondary palate may be interpreted as one of a number of methods, seen in the mammal-like reptiles, for strengthening the rostrum.
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  • 161
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    Journal of Morphology 189 (1986), S. 327-346 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Data from adult birds, crocodilians, Sphenodon, squamates, turtles, and from the chick embryo are compared to test conflicting hypotheses of homology of the deep dorsal thigh muscles of birds and other reptiles. This comparison suggests that: (1) avian Mm. iliofemoralis externus and iliotrochantericus caudalis (herein renamed “iliofemoralis cranialis”) are homologous with M. iliofemoralis of other reptiles; (2) avian Mm. iliotrochanterici cranialis and medius are homologous with one of two divisions of M. pubo-ischio-femoralis internus found in other reptiles (pars dorsalis of Crocodylia); (3) avian M. iliofemoralis internus (herein renamed “cuppedicus”) is homologous with the other division of M. pubo-ischio-femoralis internus (pars medialis of Crocodylia). This hypothesis implies a minimum of seven transformations in the number of muscles and their positions of origin and insertion in the evolution of Aves, five of which are recapitulated during ontogeny of the chick. The traditional recognition of three muscles in the “iliotrochantericus group” is topographically accurate, but it is a misnomer and has been a source of misdirection when these muscles are studied in a phylogenetic context. Variations within Aves in the presence of the iliotrochantericus muscles (cranialis or medius) and the iliofemoralis muscles (externus or cranialis) are results of heterochronic perturbations of a conserved developmental program. Unlike most previous interpretations, this view of homology suggests that the evolution of avian bipedality was accompanied by few myological transformations, despite profound modification of the skeleton.
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  • 162
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    Journal of Morphology 190 (1986), S. 1-8 
    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 was studied in chick embryos developing normally in ovo or in shell-less culture (after removal of the eggshell). Shell-less chick embryos are significantly hypocalcemic relative to their in ovo counterparts. At 12 days of incubation, the parathyroid glands of shell-less embryos contain more lipid and show evidence of increased protein synthetic activity relative to those grown in ovo (more rough endoplasmic reticulum, presence of some dense secretory granules). The glands from in ovo embryos do not contain secretory granules at this age. At 15 days of incubation, the in ovo glands have developed signs of protein synthetic activity similar to those of the 12-day shell-less embryos. However, the parathyroids of the 15-day shell-less embryos appear strikingly more active than at 12 days, containing stacks of concentric RER membranes and increased numbers of secretory granules. By 18 days of incubation, the ultrastructure of the glands of the two groups is indistinguishable, both appearing to be more active than the 15-day shell-less group. Thus, protein synthetic activity of the parathyroid glands, as detected by ultrastructural alterations of the chief cells, normally appears to be initiated during the latter part of embryogenesis (by approximately 15 days incubation) and its onset can be stimulated at least 3 days prematurely by hypocalcemia.
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  • 163
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    Journal of Morphology 190 (1986), S. 43-61 
    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 the opercularis system of anuran and caudate amphibians suggests that it acts to produce motion of the operculum that in turn produces fluid motion within the inner ear. The operculum and opercularis muscle form a lever system, with a narrow connection between the operculum and otic capsule acting as a fulcrum about which the operculum moves in response to forces applied via the muscle. The opercula of many species possess a muscular process on which the muscle inserts, thereby increasing the moment arm through which the muscle acts. The tonicity of the opercularis muscle allows tensile forces produced by substrate vibration or other mechanical energy applied to the forelimb to be effectively transmitted to the operculum; the elasticity of the connective tissue holding the operculum in place should act to return the operculum to its original position. The opercularis systems of frogs and non-plethodontid salamanders are similar structurally and functionally; that of plethodontid salamanders is structurally distinct but also functions as a lever system. Fluid motion produced by opercular motion could stimulate various end organs of the inner ear; the saccule, lagena, and amphibian papilla are in close approximation and wave energy could directly affect their otoconial or tectorial structures. In those anurans with a tympanic ear, the stapedial footplate and operculum articulate, but this articulation allows both to move independently. The stapes-tympanum complex and opercularis system therefore appear to be independent functional systems, and it is unlikely that the opercularis system modulates middle ear responsiveness. The general design of the opercularis system is consistent with a function in reception of substrate vibrations.
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  • 164
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    Journal of Morphology 190 (1986), S. 191-200 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Species of the salamander genus Plethodon have a characteristically uniform morphology. Morphological conservatism at the level of interspecific comparisons, however, is not always reflected within species. Perhaps the most extreme example of intraspecific variation is the recent description of extensive variability in limb-skeletal patterning both within and between populations of the widespread species P. cinereus. We utilized limb regeneration following experimental amputation as a tool (1) to examine whether naturally occurring variant skeletal patterns result from limb loss and regeneration in nature, and (2) to assay the intrinsic (i.e., genetic) component of between-individual variation in mesopodial patterning. We observed the following. First, regenerate patterns are strikingly different from native patterns: interelement fusions in regenerates are typically between proximodistally adjacent cartilages, whereas interelement fusions in native variant limbs occur exclusively between laterally adjacent cartilages. Fusions also are over ten times more frequent in regenerates than in native limbs. Second, there is no strong correlation between native limb pattern (typical vs. variant) and the regenerate pattern. We conclude that variability in field-collected P. cinereus reflects extensive intrapopulation variation in limb-skeletal patterning during original limb development, rather than regeneration in nature, and that limb regeneration analysis provides no evidence of a strong genetic component to between-individual variation. Finally, unusual mesopodial patterns produced during limb regeneration may be related to the mechanical factors impinging on the regenerating limb in this terrestrial species.
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  • 165
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    Journal of Morphology 190 (1986), S. 215-241 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The centra of Lepisosteus are perichondral ossifications of arcualia (i.e., arcocentra), whereas those of Amia are direct perichordal ossifications (i.e., autocentra) that enclose the arcualia. The preural centra of Lepisosteus are monospondylous, whereas the ural centra are formations of inter- and basidorsal arcualia. In contrast, the preural centra of Amia are diplospondylous, whereas preural centrum 1 (and sometimes preural centrum 2) and ural centra are monospondylous. The ural centra of Lepisosteus are expansions of dorsal arcualia, but those of Amia are expansions of the basiventral autocentrum. This explains the fusion of the neural arches with the ural centra and the presence of autogenous hypurals in Lepisosteus, in contrast to the situation in Amia in which the compound ural neural arch (the fused ural neural arches) is free, and the hypurals are fused to the ural centra. Lepisosteus possesses true epurals, which are modified neural spines, whereas in Amia the “epurals” are positioned between the neural spines like radials. Lepisosteus and Amia possess a polyural caudal skeleton with a one-to-one relationship between ural centra and hypurals; the number of hypurals may be reduced in adult Lepisosteus.
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  • 166
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Samples of perirenal adipose tissue were obtained from four fetuses from each of seven crossbred gilts at each of three stages of gestation: 70, 90, and 110 days. Samples were routinely prepared for histochemistry and histology. At each age, the largest fat cell clusters were consistently located near points where large blood vessels entered the loose connective tissue. Cell-cluster size decreased with distance from the entry points of large blood vessels. Fat cells proximal to entry points of large arterioles and fat cells distal to entry points of large arterioles were the same size. Enzyme cytochemistry disclosed that reactions for glucose-6-phosphate dehydrogenose (G6PDH), lipoprotein lipase (LPL) and NADH-TR enzymes were reduced in distal (relative to entry points of large arterioles) adipocytes compared with proximal adipocytes. Reactions for succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) in adipocytes were not influenced by location within the tissue. Small fat cell clusters with sparse capillary beds surround arterioles in distal areas of sections from fetuses at 70, 90, and 110 days of gestation. In the proximal areas of sections from 110-day-old fetuses, arterioles were surrounded by large fat cell clusters with dense capillary beds. These characteristics serve to distinguish perirenal depots from subcutaneous depots in the fetus.
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  • 167
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    Journal of Morphology 190 (1986), S. 297-305 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In an effort to understand the variation and probable origin of a female copulatory organ found in isopods of the asellote superfamily Janiroidea, the morphology of female reproductive structures among the Asellota was surveyed. Examples of four asellote superfamilies were studied using whole mount staining after potassium-hydroxide maceration or clearing with lactic acid. In contradiction to previous conclusions, the cuticular organ is shown to occur in the more primitive Asellota, although the position of its opening varies considerably. In the genera Asellus, and Stenetrium, Munna, and Santia, the cuticular organ originates adjacent to the oopore, and in the remaining janiroidean isopods, it is placed dorsally and usually anteriorly. This information permits a simple hypothesis explaining the origin of the cuticular organ: it was present in the proximate ancestor of the Asellota and evolved to the janiroidean condition by anterodorsal migration.
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  • 168
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    Journal of Morphology 190 (1986), S. 325-333 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The spinal cord of two tetraodontiform fishes, the Japanese file fish (Navodon modestus) and the panther puffer (Takifugu pardalis), are unusual among vertebrates in having a markedly abbreviated spinal cord with a long and flattened filum terminale. Only the rostral short part of the cord of both species is cylindrical; the greater part of the cord is markedly flat. The majority of the spinal nerve roots leave the short cylindrical part. The flattened part of the cord contains the central canal, myelinated nerve fibers, and a few motoneurons surrounding the cauda equina, and it is histologically similar to the filum terminale of amphibians and mammals. The spinal cords of other teleosts, the sun-fish and angler, also are abbreviated and possess a filum terminale and cauda equina. These orders possess an enormous head and short trunk. However, the correlation between this body form and an abbreviated cord is not causal, since the tetraodontiform species described here show ordinary body proportions. The spinal cord may be abbreviated in tetraodontiform fishes in general.
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  • 169
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    Journal of Morphology 190 (1986), S. 237-248 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Estivation in Protopterus is an episodic event characterized by elaboration of a cocoon as ambient water is withdrawn, a state of torpor, and distinctive cardiorespiratory and metabolic changes. Among the more striking of these features is a decrease in oxygen consumption, a complete reliance on air breathing to satisfy metabolic need, a slowing of the heart rate, and a drop in blood pressure. The initiating mechanism for these dramatic changes is not known. As yet, specific “estivating factors” have not been identified. However, the pattern of decrease in oxygen uptake during estivation and starvation are quite similar, suggesting that a common factor may be involved in both. Attempts to implicate suppression of thyroid function in the onset of estivation have been unconvincing. Although initiating mechanisms for estivation in Protopterus remain uncertain, once estivation sets in a variety of adaptive changes occur that enable the estivating lungfish to survive for months to years without ingesting food or water. Among these are oliguria and a shift in metabolic pathways. Although estivation in Protopterus has been characterized with respect to cardiorespiratory and metabolic parameters, no attempt is made to extrapolate from the biologic processes in Protopterus to other lepidosirenid lungfish or to other genera.
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  • 170
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    Journal of Morphology 190 (1986), S. 305-373 
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  • 171
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    Journal of Morphology 187 (1986) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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  • 172
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    Journal of Morphology 187 (1986), S. 1-21 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The cephalic muscles in three species of Entechinus, two species of Opheodrys, and Symphimus mayae display patterns of interspecific variation that are largely congruent with patterns of variation previously described for the skulls of these species. This congruence does not stem from direct correlation between the shapes of associated bones and muscles. In these colubrid snakes, most interspecific variations in muscle form involve changes in the shape or relative position of attachment points that appear unrelated to changes in the gross form of the bony surfaces forming the attachment points and produce no major changes in the architectural array of fibers in the muscle. Data presented here, combined with information from previous comparative studies of colubroid cephalic muscles, support the hypothesis that these muscles are limited in their potential variability by factors favoring parallel arrangements of fibers.
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  • 173
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    Journal of Morphology 187 (1986), S. 51-60 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Formation of lateral vessels in the esophageal region of Prosorhochmus americanus embryos and coelomogenesis in the pygidial region of larval Magelona sp. are examined and compared. Earliest vessel rudiments of P. americanus are composed of a compact band of mesodermal cells (mesodermal band), lying on a layer of extracellular matrix (ECM) and lacking intercellular junctions. Rudiments are surrounded by presumptive muscle cells. Rudiments at later stages of differentiation possess lumina of differing sizes formed by a separation of apposing cell apices (schizocoely). Aohagrens junctions are apparent between lining cels of vessels following cavitation, and overlying muscle cells exhibit many myofilaments. Mesodermal bands of the recognized coelomate, Magelona sp. consist of glycogen-rich, mesodermal cells resting on ECM and joined by adhaerens junctions. Some of the cells possess a rudimentary cilium. Coelom formation occurs as a splitting of the cell band as is the case for P. americanus. Recognition of an accepted mode of coelomogenesis in P. americanus, correlated with morphological details of adult nemertine vessels, affirms the view that nemertine vessels are coelomic homologues.
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  • 174
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    Journal of Morphology 187 (1986), S. 23-37 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Eggs of the asteroid Pisaster ochraceus demonstrate cortical granules, a thick vitelline membrane, and a poorly stained jelly coat similar to that seen on the eggs of other echinoderms. When fixed in the presence of alcian blue the jelly coat is seen to be made up of three regions, an inner layer consisting of a meshwork of fibres, a middle layer of thicker fibres, and a dense outer layer. At fertilization the cortical granules release their contents into the potential space between the vitelline layers and a low fertilization membrane consisting of the vitelline layer and a dense component of the corticle granule is formed. Initially the remaining contents of the corticle granules form an amorphous hyaline layer that fills the space between the plasma membrane and the fertilization membrane. At hatching a distinct hyaline layer is present. It persists at least to the bipinnaria stage and consists of four distinct layers. A similar layer is also located over much of the early embryonic endoderm but is lost from the regions involved in the formation of the mesenchyme cells, coelom, and mouth just before these events take place. Numerous large clear vesicles are located in the apex of all cells associated with a hyaline layer. Where the hyaline layer is lacking, only scattered vesicles are present suggesting that the vesicles may be involved in maintenance of the layer. Attempts to identify elements of the hyaline layer by immunofluorescence demonstrated that it appears to bind both antisera and control sera in a nonspecific manner.
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  • 175
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    Journal of Morphology 187 (1986), S. 39-49 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Six fiber types have been described in the ambiens muscle of red-eared turtles. These include one slow oxidative type, two fast oxidative types, two fast oxidative and glycolytic types, and one fast glycolytic type. Fiber types are non-randomly distributed throughout cross sections of the muscle. There is a decreasing gradient of oxidative staining and an increasing gradient of glycolytic staining along an axis from the superficial to deep regions of the muscle. The slow oxidative fibers are predominantly located within one or two fascicles of the superficial surface of the muscle. The fast glycolytic fibers are predominant in deep fascicles.In contrast to previous reports of histochemically monotypic intrafusal fibers in turtle muscle, ambiens muscle spindles have been observed containing one to eleven intrafusal fibers, including two fiber types. Fiber diameter and area are consistently smaller than observed in most extrafusal fibers. Spindles are predominantly located in superficial and cranial fascicles of the ambiens muscle and are located in regions characterized by extrafusal fibers with high oxidative activity.
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  • 176
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    Journal of Morphology 187 (1986), S. 109-121 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Ultrastructural examination of the head kidney of Periophthalmus koelreuteri (Pallas) (Teleostei, Gobiidae) revealed that the nephronic tubule cells are bound by tight junctions and desmosomes with little intercellular space. The first proximal segment (PI) consists of low columnar cells with well developed brush borders, indented nuclei, and numerous apical endocytic vesicles and lysosomes. A second cell type possessing clusters of apical cilia and lacking brush border and lysosomes is occasionally found between PI cells. The second proximal segment (PII) is formed of high columnar cells with brush border, regular spherical nuclei and numerous mitochondria located between well developed infoldings of the basal membrane. Single ciliary structures protrude into the lumen from PI and PII cells. The distal segment is lined by low columnar epithelium with few microvilli, regular spherical nuclei, numerous scattered mitochondria, and microbodies. The collecting tubule cells are cuboidal with few euchromatic nuclei, some mitochondria, and secondary lysosomes.
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  • 177
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  • 178
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    Journal of Morphology 187 (1986), S. 81-108 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The feeding mechanism of the South American lungfish, Lepidosiren paradoxa retains many primitive teleostome characteristics. In particular, the process of initial prey capture shares four salient functional features with other primitive vertebrates: (1) prey capture by suction feeding, (2) cranial elevation at the cranio-vertebral joint during the mouth opening phase of the strike, (3) the hyoid apparatus plays a major role in mediating expansion of the oral cavity and is one biomechanical pathway involved in depressing the mandible, and (4) peak hyoid excursion occurs after maximum gape is achieved.Lepidosiren also possesses four key morphological and functional specializations of the feeding mechanism: (1) tooth plates, (2) an enlarged cranial rib serving as a site for the origin of muscles depressing the hyoid apparatus, (3) a depressor mandibulae muscle, apparently not homologous to that of amphibians, and (4) a complex sequence of manipulation and chewing of prey in the oral cavity prior to swallowing. The depressor madibulae is always active during mouth opening, in contrast to some previous suggestions.Chewing cycles include alternating adduction and transport phases. Between each adduction, food may be transported in or out of the buccal cavity to position it between the tooth plates. The depressor mandibulae muscle is active in a double-burst pattern during chewing, with the larger second burst serving to open the mouth during prey transport. Swallowing is characterized by prolonged activity in the hyoid constrictor musculature and the geniothoracicus.Lepidosiren uses hydraulic transport achieved by movements of the hyoid apparatus to position prey within the oral cavity. This function is analagous to that of the tongue in many tetrapods.
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  • 179
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    Journal of Morphology 187 (1986) 
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  • 180
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    Journal of Morphology 187 (1986), S. 239-246 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: In addition to the cholinergic innervation described in the sphincter of the efferent filament arteries (Bailly and Dunel-Erb, ′86), an aminergic component has been demonstrated by specific techniques. The Falck fluorescence technique reveals a network of nerve fibers displaying a green fluorescence characteristic of catecholamines. At the ultrastructural level two types of fibers are present, one with clear vesicles and another with densecored vesicles. Axo-axonal synaptic relationships exist between the two types. Results of 5- and 6-OHDA (hydroxydopamine) treatments confirm the presence of an aminergic component.These observations support the notion of a dual innervation: cholinergic and adrenergic of, respectively, parasympathetic and sympathetic origin. The presence of presynaptic modulation is suggested. The aminergic component could inhibit or reduce the release of acetylcholine from cholinergic nerve endings. These results suggest that the sympathetic innervation modulates the vasoconstriction effect of the parasympathetic component.
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  • 181
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    Journal of Morphology 187 (1986), S. 143-158 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Among the acanthopterygian fishes, the Labridae possess the most highly integrated and specialized pharyngeal jaw apparatus. The integrated feature involves many osteological components and aspects of muscle form, architecture, composition, and function. The upper jaw articulates by means of a true diarthrosis with the pharyngeal process of the parasphenoid, whereas the lower jaw has established physical contact with the cleithrum. Complex muscle fusions have contributed significantly in the development of a double muscle sling operating the lower jaw. The original levator externus 4 fuses with the central head of the obliquus posterior, whereas the original levator posterior combines with the lateral head of the obliquus posterior as well as with the adductor branchialis 5.During the masticatory cycle, both upper and lower jaws undergo complex movement orbits resulting in shearing and crushing functions. Shearing occurs as the forward moving upper jaw collides with the dorsally held lower jaw. Crushing is effected by an extreme posterodorsal movement of the lower jaw against the retracted upper jaw, thereby establishing full occlusion of the teeth.The specialized morphological and functional design of the labrid pharyngeal jaw apparatus is similar to that found in cichlids. In sharp contrast to primitive acanthopterygian fishes, the Labridae and Cichlidae exhibit a spectacular morphological diversity that parallels their ecological diversification. Our combined functional and historical analysis has established a correlation between the complex integration of the pharyngeal jaw apparatus and morphological and ecological diversity in the Labridae and Cichlidae.
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  • 182
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    Journal of Morphology 187 (1986), S. 219-237 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Previous studies have shown the existence of a sphincter in the efferent filament artery of the teleost gill and its constrictory response to acetylcholine (ACH) and vagal stimulation. This study deals with the muscular organization of this sphincter and the distribution of its innervation as elucidated by degeneration methods and cytochemistry. The sphincter innervation is supplied by the protrematic vagus nerves. Nerve endings filled with cholinergic-type vesicles are located in close association with the adventitial smooth muscle cells and display a strong acetylcholinesterase (ACHE) activity. Section of the protrematic vagus nerve induces a nearly complete degeneration of the sphincter innervation. ACHE-positive nerve cell bodies are present both in the sphincter area and in the protrematic vagus nerve. These results suggest that innervation of the sphincter in the efferent filament artery is cholinergic through the activity of postganglionic axons of the parasympathetic system.
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  • 183
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    Journal of Morphology 187 (1986), S. 289-299 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Dramatic depression in granule volume density and size was measured in acinar cells of postnatal rat pancreas following the initiation of feeding. Volume density decreased about threefold from 45% at birth to 16% 2 days thereafter. Mean granule diameter decreased from 1.50 μm to 0.80 μm, an 85% decrease in corresponding granule volume. At the same time, numerical density approximately doubled. At 2 days after birth, cells with smaller granules had lower volume densities, and differences in mean granule volume between cells accounted for most of the differences in volume density. Although the distribution of granule diameter in newborns was lognormal, the distribution at 2 days was heavily skewed to larger sizes. This was the result of skewed distributions within individual cells and not an artifact of sampling. The results corroborate the central role of granule volume in determining changes in the volume density of zymogen granules in the pancreas and suggest that zymogen granules can act as capacitors that can change size as a function of the enzyme contained within.
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  • 184
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    Journal of Morphology 187 (1986), S. 321-342 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A comparative study of four genera of arvicolid rodents (Clethrionomys, Eothenomys, Alticola, and Synaptomys) presents the first complete description of limb myology for any member of this recently evolved, highly successful family. The study also identifies four forelimb and four hind-limb muscles that exhibit characters of value to systematic analyses within the group. In no instance was postcranial myology sufficient to distinguish among species of Clethrionomys or to distinguish Clethrionomys from Eothenomys. Moreover, in some instances Synaptomys, a genus traditionally presumed primitive within the family, possessed the apomorphic condition for a myological character when compared to the four genera of cricetine rodents that served for outgroup comparisons.
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  • 185
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    Journal of Morphology 188 (1986), S. 15-28 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Egg capsules of Syndisyrinx franciscanus, an intestinal parasite of sea urchins (Strongylocentrotus spp.), consist of a bulb, which contains the embryos, and a stalk-like filament. The wall of the bulb is about 12 μm thick and is composed of sclerotized proteins. The end of the bulb opposite the attachment of the filament bears a reticulum of hatching sutures. Transmission electron microscopy discloses that hatching sutures traverse the entire thickness of the capsule wall. The inner 9-10 μm of sutures are a uniform 20 nm in width and contain a trilaminar cementum. The outer 2-3 μm of sutures are 15 nm to more than 500 nm in width and contain an electron-lucent cementum. The latter may contain an irregular, median, electron-dense layer or, more commonly, electron-dense granules. The outside of some capsules is partially covered by a thin, electron-dense material.A previous study showed that sutures in intact capsules of Syndisyrinx franciscanus are not affected by host digestive fluids, but are severely weakened immediately prior to hatching owing to activities of the embryos. The hypothesis that the embryos secrete a hatching enzyme is supported by findings that sutures of intact capsules are not affected by externally applied trypsin, but become weakened when capsules are cut open and then incubated in trypsin. Scanning electron microscopy reveals that the outer parts of sutures often remain intact after hatching. We hypothesize that the ability of sutures to resist enzymatic attack from the outside, but not the inside, results from differences in the chemical properties of the cementums in outer and inner parts of sutures.
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  • 186
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    Journal of Morphology 188 (1986), S. 225-238 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The iris of the toad Bufo marinus is directly photosensitive and will constrict in response to light striking only the iris. This is true even when the iris is isolated from the rest of the eye, and therefore from reflex neuronal influences initiated in the retina. This autonomous response is probably mediated by the sphincter pupillae muscle, since no specialized photoreceptors are present in the iris, nor does the sphincter exhibit any specializations likely to subserve a purely photoreceptive function. The photosensitive sphincter appears typical of smooth muscle and, like mammalian sphincters, possesses many intercellular junctions. The iris possesses a well-developed neuronal plexus with fibers projecting into the sphincter muscle layer. Nerve terminals contain small, agranular (30-70nm) and large, dense-cored (80-120nm) vesicles. No consistent postsynaptic specializations are seen on any cells of the iris, including the cells of the sphincter muscle. The anterior pigment epithelial cells of the iris appear specialized and resemble the myoepithelial dilator muscle described by Kelly and Arnold ('72) for the iris of rats.
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  • 187
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    Journal of Morphology 188 (1986), S. 289-302 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The cell-lineage of Bithynia tentaculata L. has been studied through the formation of the fourth quartet of micromeres, i.e., the 81-cell stage. Up to the 28-cell stage, the cleavage pattern is radially symmetrical, and the divisions take place synchronously in the quadrants. Bilateral symmetry is established by the formation of the mesentoblast 4d at the future dorsal side. A resting stage preceding the formation of 4d is lacking. The mesentoblast 4d is formed earlier than the other fourth quartet cells, and it divides twice before 4a-4c are formed. Bilateral symmetry in the molluscan cross becomes apparent by different divisions of the tipcell and the basal cell in the dorsal arm. Dorsoventrality is progressively corroborated by the divisions in the second and third quartets of micromeres, which take a different course in the A and B quadrants on the one side and in the C and D quadrants on the other side.
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  • 188
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    Journal of Morphology 188 (1986), S. 303-313 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Two modes of shedding of rod disc membranes were observed by electron microscopy in bullfrog retinas illuminated for various periods from 10 min to 2 hr. One mode is “autonomous shedding” whereby rods shed disc packets directly into the subretinal space. Most of the discarded disc packets are subsequently brought into contact with villous apical processes of pigment epithelial (PE) cells and are ultimately engulfed by these cells. When some of the shed disc membranes remain in the subretinal space, it appears that these remanants may be phagocytized by ameboid phagocytes. The other mode is “cooperative shedding” whereby rods shed disc packets with the participation of pigment epithelial ensheathment. Shedding of a disc packet from a rod tip, and enclosing of the rod tip by a broad, sleeve-like apical process of a PE cell, take place simultaneously. The separated disc packets may be immediately engulfed by the PE cells without risk of failure. Both villous and sleeve-like types of apical processes of PE cells in the bullfrog lack pigment granules, in contrast to the finger-like apical processes that do contain pigment granules. Villous and sleeve-like apical processes that do contain pigment granules. Villous and sleeve-like processes therefore probably belong to the same category as the leaf-like apical processes of PE cells in mammalian retinas.
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  • 189
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    Journal of Morphology 189 (1986) 
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  • 190
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    Journal of Morphology 189 (1986), S. 25-43 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: High-speed cinematography shows that Suncus murinus (Crocidurinae) masticates fast (mean 5.5, 5-10 masticatory cycles per sec). Their grasping behavior is not stereotyped. The unilateral mandibular movements combine vertical, anteroposterior, and lateral displacements; and any masticatory sequence may include crushing, repositioning, shearing, and grinding components. Size and consistency of food influence the duration of individual chewing cycles. As food is transferred to the new working side, the chewing direction reverses, either near maximum closure or near maximum opening. An unfused mandibular symphysis permits tilting movements of the two halves of the mandible. Food may be squeezed between the lower incisors. The working side tilts outward during closing; this may improve shearing or grinding action. The closing phase is posteriorly directed. Thus, the masticatory movements of these shrews differ from those that have been described in many other mammals.
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  • 191
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    Journal of Morphology 189 (1986), S. 67-70 
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The presence of adrenergic innervation was investigated in four different vascular segments of the neotenic tiger salamander, Ambystoma tigrinum, by histofluorescent staining for catecholamines. The segments were the respiratory section of the gill, the branchial shunt vessels, a vascular plexus in the pulmonary artery, and the dorsal aorta. No adrenergic fibers were detected in the respiratory section of the gill or the pulmonary arterial plexus. In contrast, the branchial shunt vessels contained both adrenergic varicosities and catecholamine-containing cell bodies. These cells resemble Type I cells of the mammalian carotid body and amphibian carotid labyrinth. Adrenergic innervation of the dorsal aorta was sparse and restricted to the adventitia. The results suggest that adrenergic nerves may directly regulate blood flow in the gill, and thus gas exchange, by controlling vascular resistance of the branchial shunts. The contractile state of the dorsal aorta may also be under adrenergic control. In addition, it is suggested that the adrenergic cells of the branchial shunts may serve a receptor function in being sensitive to arterial blood gases.
    Additional Material: 6 Ill.
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  • 192
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    Journal of Morphology 189 (1986), S. 89-98 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Scanning and light microscopy investigations of the anterior alimentary canal of the pear psylla, Psylla pyricola Foerster (Homoptera: Psyllidae), revealed the morphology of the labium and stylets, as well as the presence of sensory structures and a valve in the precibarium. The labium consists of three telescoping segments with an internal labial groove, which surrounds and supports the stylet bundle. Also a part of the labial groove is the internal labial clamp. The stylet bundle is comprised of paired styliform mandibles and maxillae, which interlock to form the food and salivary canals. The stylet bundle proximal to the labium forms a large loop within a membranous crumena. When fully retracted the coiled stylets are under tension. Stylet extension generates increasing tension so that when retracted the stylets readily recoil within the crumena. Penetration of leaf tissues by the stylet bundle is dependent on the interaction between stylet muscles, opening and closing of the labial clamp, the barbed stylet tips, and the ventral position of the labium.Proximal to the crumena the paired stylets separate and diverge at the entrance of the precibarium, which is formed by the interlocking of the epi-and hypopharynges. There are 18 sensory structures in the precibarium, as well as a precibarial valve. These structures appear to be homologous to similar structures observed previously in aphids and leafhoppers. The morphology and the location of the precibarial sensilla suggest that, like the precibarial sensory organs of aphids and leafhoppers, they are gustatory and probably mediate acceptance or rejection of plant fluids, thus playing a major role in locating tissues for feeding.
    Additional Material: 6 Ill.
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  • 193
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    Journal of Morphology 189 (1986), 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: In seven species of lungless salamanders, family Plethodontidae, ranging from medium to very small in body size and from small to very large in cell size, the morphology of the eye and the retina were investigated. Haller's rule was only partially corroborated. While the smallest species had the relatively largest eyes, the largest two species, having the largest cells, showed the third and fourth largest eyes of the series. An effect of cell size was also found with regard to eye morphology. Small species with small cells as well as large species with large cells had relatively small retinae and relatively large lenses. In contrast, small eyes with relatively large cells had absolutely and relatively large retinae and relatively small lenses.The retinae of all investigated plethodontids showed a morphology typical for land vertebrates with two fiber and three nuclear layers. Rods, cones and double cones could clearly be distinguished. A fovea or area centralis was not found. Retina ganglion cell and photoreceptor counts show that the number of these elements was lower than in salamandrids. However, determination of the resolution power of miniaturized eyes based on morphological and behavioral data shows that this does not seem to constitute a functional disadvantage. The morphological and functional properties and constraints of eyes of miniaturized salamanders are discussed.
    Additional Material: 6 Ill.
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  • 194
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    Journal of Morphology 189 (1986), S. 189-197 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cells considered to be migratory in the cerebral cortex of adult lizards are ultrastructurally of two types. Nuclei in the first type have highly dispersed chromatin, creating a spongy appearance, whereas in the second type the chromatin is irregularly clumped. Both types of cells are closely associated with processes of radial ependymal glia cells, which perhaps orient their migratory pathways. Cells with spongy chromatin show an increase in cytoplasmic organelles and progressive chromatin condensation as they travel from the ependymal layer to the granular layer. Possibly these cells account for the neuronal increase that takes place in the granular layer during postnatal life. Cells with chromatin clumps are very scarce; ultrastructurally they resemble immature reptilian astroglia cells.
    Additional Material: 8 Ill.
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  • 195
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    Journal of Morphology 188 (1986), S. 335-346 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The medulla of renculi from kidneys of Ringed seals (Phoca hispida) is completely enclosed by cortex except at the hilum. Within the renculus, the fibromuscular coat of the calyx separates from the transitional epithelium at the level of the corticomedullary junction, where the intrarencular arteries also diverge into the parenchyma. Flat ribbons of this stromal tissue form an arborized framework near the medullary side of the intrarencular arteries and the larger of the arcuate arteries derived from them. The ribbons, which are clearly distinct from periarterial connective tissue, are composed of coarse collagenous fibers, elastic fibers, and smooth muscle cells, all oriented in the direction of the long axes of the ribbons, and myofibroblasts. The proportion of smooth muscle cells decreases and that of myofibroblasts increases with increasing distance from the calyx. At the base of the medullary pyramid, the elements of the framework diminish in width and ultimately blend with the surrounding interstitial tissue. The stromal framework, or basket, is homologous with the Sporta perimedullaris musculosa of cetacean kidneys.
    Additional Material: 6 Ill.
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  • 196
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    Journal of Morphology 188 (1986), S. 347-361 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A morphological comparison was made of the green livers of male and female lampreys (Petromyzon marinus L.) collected during the upstream (prespawning) migration. Light and electron microscope histochemistry for iron, and both thin sections and freeze-fracture replicas in the electron microscope, revealed some sexual dimorphism in these livers. Ferric iron is much more abundant in the liver of females and is present in the cytoplasmic matrix, in dense bodies, and in vacuoles of hepatocytes. The numerous vacuoles of females may be the deposition site of biliverdin and other bile components that would account for the darker green coloration of the liver compared to males. Hepatocytes in females are also characterized by prominent rough endoplasmic reticulum and Golgi apparatus that reflect the involvement of the cells in vitellogenesis. The presence of numerous lipid droplets in the hepatocytes of males indicates that the liver is an important storage site for fat. The lipid droplets are associated with electron-dense deposits of unknown nature. Large gap junctions typify the parenchymal cells of both male and female livers. Perisinusoidal and sinusoidal cells are similar to those in the nonparenchymal region in other vertebrate livers, namely, endothelial and Kupffer cells, lipocytes (Ito), and some granulated cells. The relationship of lipocytes to fibrous tissue and fibrogenesis is discussed.
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  • 197
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    Journal of Morphology 189 (1986), S. 17-24 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The fine structure of the hemocytes and nephrocytes in Argas (Persicargas) arboreus is described and compared with that of similar cells in other tick species and insects. The hemocytes are of three types: prohemocytes, with a relatively undifferentiated cytoplasm lacking granular inclusions and probably serving as progenitors of the other hemolymph cell types; plasmatocytes, containing abundant mitochondria, cisternae of rough endoplasmic reticulum (RER), and free ribosomes, as well as some small granular inclusions; granulocytes, the predominant cell type in the hemolymph, containing numerous granules of variable electron density and maturity, and pseudopodia-like processes on the cell surface. Plasmatocytes and granulocytes are phagocytic and possibly also have other functions in the tick body. Cells with intermediate features appear to be in a stage of transition from plasmatocyte to granulocyte.Nephrocytes contain vacuoles enclosing fibrillar material, some electrondense granules, and moderate amounts of the active organelles - mitochondria, RER, and ribosomes. The nephrocyte is surrounded by a basal lamina and its plasma membrane infolds to form many deep invaginations coated by a fine fibrillar material. Openings to these invaginations are closed by membranous diaphragms. Coated tubular elements connect the surface invaginations with large coated vesicles, which appear to be specialized for internalization of proteins from the hemolymph. The dense granules may represent an advanced stage of condensation of ingested protein and thus may be lysosomal residual bodies, or they may develop by accumulation of secretory products.
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  • 198
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 189 (1986) 
    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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  • 199
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    Journal of Morphology 189 (1986), S. 121-129 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In this study we examined the possible inductive role of the dental papilla from polyphyodont lizard tooth germs. Flank skin sheets of quail ectoderm enzymatically separated from dermal tissue were recombined with lizard tooth papillae and placed on semisolid medium and cultured for 2 days. Subsequently, the recombinants were removed and placed on the chorioallantoic membrane of chick hosts and incubated for 6 days. After this period of 8 days in explant, control tissues differentiated according to their own phenotypes. Lizard dental papilla alone differentiated as fibroblasts. Quail flank skin ectoderm differentiated into epithelial sheets. Intact lizard tooth buds developed into teeth with dentine and incipient enamel. In the best experimental recombinants, advanced and relatively well-constructed teeth were observed, with clear indications of hard tissue deposition in association with quail epithelium. The results show that mesenchyme of the adult lizard dental papilla and embryonic quail ectoderm of heterotopic origin are capable of carrying out the complex sequence of morphogenetic interactions involved in normal odontogenesis.
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  • 200
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    Journal of Morphology 190 (1986), S. 63-71 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Sperm development in Ornithodoros (Pavlovskyella) erraticus includes the formation of subsurface cisternae in the primary spermatocytes, which divide meiotically to secondary spermatocytes and ultimately to spermatids. During spermiogenesis the spermatid undergo morphological transformation including polarization of the nucleus and subsurface cisternae, formation of a cisternal tube, and modification of the subsurface cisternae to cellular processes surrounded by cisternal vesicles. Further transformation occurs after spermatids are introduced into the female. The spermatid cisternal tube now invaginates to form an inner cord surrounded by an outer sheath. The invaginated inner cord elongates anteriorly as the outer sheath continues to invaginate posteriorly during spermiogenesis. With further elongation, the spermatid membrane ruptures anteriorly, leaving the inner cord exposed as the outer surface of the maturing sperm. Posteriorly, the original plasma membrane invaginates to form an acrosomal canal which becomes surrounded by an acrosome. The hemispherical anterior end of the mature sperm is covered with rows of projections separated from the remainder of the sperm by a row of fringed processes. Except for the posterior end, the rest of the sperm is covered by longitudinally distributed electron-dense cellular processes and an outer mat of more electron-lucent tubular elements. Mitochondria and bundles of microfibrils are found beneath the cellular processes. Microfibrils are suggested to be the principal contractile organelles responsible for sperm motility. Cellular processes appear to be the main external motile structures, while movements of tubular elements and fringed processes may also contribute to sperm motility.
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