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  • pharmacokinetics  (48)
  • Synapses  (37)
  • Springer  (85)
  • Essen : Verl. Glückauf
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • 2015-2019
  • 2005-2009
  • 1970-1974  (85)
  • 1940-1944
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 7 (1974), S. 407-414 
    ISSN: 1432-1041
    Keywords: Diuretic ; indapamide ; human pharmacology ; toxicology ; pharmacokinetics ; TLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na+, K+ and Cl− and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca2+, Mg2+ and PO 4 3− rose in spite of a fall in urinary concentrations of these ions. The Ca2+ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.
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  • 2
    ISSN: 1432-1041
    Keywords: Oral antidiabetic drug ; butylbiguanide ; pharmacokinetics ; two-compartment open model ; plasma concentration ; liver concentration ; intestine concentration ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 50 mg14C-Butylbiguanide was administered intravenously to 4 diabetic patients and 100 mg14C-butylbiguanide orally to 5 further diabetics. The concentrations of the drug in plasma, intestinal fluid, intestinal epithelium and liver tissue were determined and the renal excretion of the biguanide measured. Irregularities in the plasma concentration curve were observed which appeared as systematic deviations from the ideal curve of a biexponential function. Because these deviations occurred only in the middle phase of the plasma concentration curve, it was nevertheless possible to calculate the pharmacokinetic parameters of butylbiguanide by use of a two-compartment open model. The principal pharmacokinetic parameters were determined according to this model after intravenous dosing and the following mean values were obtained:t 1/2 (β)=4.6 h (β=0.15 h−1),C P 0 =0.85µg/ml,V D =218 l,V T =157 l,V P =62 l,k 12=0.69 h−1,k 21=0.44 h−1,k el =0.54 h−1. Within 48 h after administration, an average of 72.4% of the intravenous and 74.4% of the oral dose had been excreted in the urine. Total clearance (Cl tot) averaged 536 ml/min and renal clearance (Cl ren) 393 ml/min. High concentrations of butylbiguanide were observed in the intestinal fluid (100–700 mg/ml) 20–40 min after oral administration. It was found that the drug accumulates in intestinal fluid, intestinal epithelium and liver tissue, and that it is secreted into the intestinal lumen. The concentrations of butylbiguanide in intestinal and liver tissue were 10–46 times higher than in plasma. The secretion of biguanide into the intestinal lumen may occur via the bile or the intestinal mucosa, but there is no evidence of significant biliary excretion of butylbiguanide.
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  • 3
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    European journal of clinical pharmacology 7 (1974), S. 295-305 
    ISSN: 1432-1041
    Keywords: Mestranol ; ethynyloestradiol ; contraceptive compounds ; demethylation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oestrogenic activity of mestranol depends on its demethylation to ethynyloestradiol. The reaction has been studied in man. The compound disappeared exponentially from plasma during the first 4 h after i.v. injection of [4-14C-] mestranol. The “metabolic clearance” for this phase amounted to 31.8 1/day per kg body weight. Methoxy-3H-labelled mestranol was prepared for the further studies, because if it is demethylated, the tritium would be transferred to HTO, which would equilibrate immediately with body water. The appearance in body water of tritium from [methoxy-3H-] mestranol could be described by two exponential functions, which corresponded to bi-phasic disappearance of the original compound from plasma. The rate constant of the first stage was: γ1=0.835 h−1, and of the second: γ2=0.034 h−1. HTO radioactivity was eliminated from the body by exchange of water. From the data obtained, a three-compartment model was constructed of the transfer of tritium from [methoxy-3H-] mestranolinto body water, which permitted computer simulation of the partial processes. The compartmental analysis suggested that mestranol differed from ethynyloestradiol mainly in the delayed and protracted manner in which hormonally active oestrogen entered the circulation. The proportion of [methoxy-3H-] mestranol demethylated to ethynyloestradiol (demethylation ratio) varied little, 53.7±5.0% (x±SD; n=6), and was consistent with clinical observations that mestranol is half as potent an oestrogen as ethynyloestradiol. Thus, the dose of mestranol required to produce a given effect has to be twice as large as that of ethynyloestradiol.
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  • 4
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    European journal of clinical pharmacology 7 (1974), S. 375-380 
    ISSN: 1432-1041
    Keywords: Tranexamic acid ; pharmacokinetics ; man ; antifibrinolytic agents ; renal clearance ; two-compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tranexamic acid has been investigated in two healthy volunteers. The behaviour of the drug can be described in terms of a two compartment open model; the disposition (biological) half-life was 2.7 h and 1.9 h, respectively. In five normal volunteers the mean total recovery in urine 48 h after dosing was 94.8%. The renal clearance in the two subjects, adjusted to 1.73 m2 body surface area, was 135 and 132 ml/min/1.73 m2, respectively, indicating that tranexamic acid is eliminated by glomerular filtration and that neither tubular excretion nor absorption takes place.
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  • 5
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    European journal of clinical pharmacology 7 (1974), S. 381-385 
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; plasma half-life ; gas chromatographic analysis ; intra-individual variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intra-individual variability in the plasma half-life of phenazone has been studied in 16 healthy, young volunteers. Phenazone was analysed by a simple gas chromatographic method, which is specific in relation to known metabolites; 4′-methylphenazone was employed as the internal standard. Phenazone was given on two occasions, two or three months apart, in oral doses of 10 mg/kg. The plasma half-life determined from five time points was 10.9±1.5 h and 11.2±1.3 h respectively, on the two occasions. The mean intra-individual variability (0.86 h) was close to the methodological error of 4%.
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  • 6
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    European journal of clinical pharmacology 7 (1974), S. 25-29 
    ISSN: 1432-1041
    Keywords: Pindolol ; uraemia ; pharmacokinetics ; β-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of pindolol in 25 patients with various degrees of renal failure has been studied after an intravenous dose of 3 mg. A linear correlation was not found between the elimination rate of pindolol and the endogenous creatinine clearance, and the half-life of the unchanged drug was independent of the severity of the renal failure. This implies greater metabolism of pindolol in anuric patients and the extrarenal elimination rate constantk mwas increased. Three patients with severe renal failure were given 3 mg14C-pindolol. They showed almost constant plasma levels of radio-activity for 6 h and then slow excretion with a half-life of 48 h, because of accumulation of metabolites in the blood. Up to 90% of the metabolites are glucuronides and sulphates which have no beta-blocking or other clinical activity. Thus, to produce beta-adrenergic blockade the same dose of indolol is required in healthy patients as in those with uraemia.
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  • 7
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    European journal of clinical pharmacology 7 (1974), S. 59-60 
    ISSN: 1432-1041
    Keywords: Pizotifen ; isonicotinylhydrazine ; orexigen ; tuberculosis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pizotifen (BC 105) has an orexigenic effect in patients with pulmonary tuberculosis. As these cases are often treated with isonicotinylhydrazine (INH), any effect of one of these drugs on the absorption of the other has been examined in a cross-over study in 8 healthy male volunteers. No difference was found between the absorption of INH given alone or together with pizotifen. It should be safe, therefore, to employ the combination of the orexigenic drug and INH in the treatment of tuberculosis as there will be no change in the concentration of therapeutic drug achieved.
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  • 8
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    European journal of clinical pharmacology 7 (1974), S. 31-37 
    ISSN: 1432-1041
    Keywords: Diphenylhydantoin ; uraemia ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diphenylhydantoin (2 mg/kg) was infused intravenously in four uraemic patients and four healthy volunteers and its plasma concentration measured during and after the infusion. The plasma concentrations were considerably lower in the uraemic subjects and the apparent volume of distribution was higher. These observations could be explained by the lower plasma protein binding of diphenylhydantoin in the uraemics. The overall elimination rate constant β was greater (shorter half-life) in the uraemic patients. This difference could not be explained by reduced plasma protein binding, but it might be due to induction of diphenylhydantoin metabolism in the uraemic state. it is concluded that monitoring of the plasma levels of drugs in uraemic patients should be combined with determination of the extent to which the compounds are bound to plasma proteins.
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  • 9
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    European journal of clinical pharmacology 7 (1974), S. 51-58 
    ISSN: 1432-1041
    Keywords: Rifampicin ; plasma level ; pleural fluid concentration ; microbiological assay ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of rifampicin (RMP) were given to 31 patients with pleural effusions of various aetiologies. The concentrations of RMP and its active metabolites in pleural fluid and plasma were determined by an agar diffusion method using paper discs as diffusion centres. The plasma concentrations reached a peak within 3 h and then declined monoexponentially; in pleural fluid, RMP concentration rose slowly to reach a plateau that lasted for several hours. There were marked differences between subjects in the observed concentrations of RMP. During the first 12 h the plasma levels exceeded those in pleural fluid, but after 24 h the concentration of RMP in pleural fluid was higher than in plasma. If multiple oral doses of RMP 10 mg/kg b. w. are given every 24 h, as is common in the treatment of tuberculosis, therapeutic concentrations may be expected in pleural fluid for the major part of each day.
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  • 10
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    European journal of clinical pharmacology 7 (1974), S. 17-24 
    ISSN: 1432-1041
    Keywords: Pindolol ; beta-blockade ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of absorption, distribution and excretion of pindolol have been investigated in 17 volunteers after an oral dose or intravenous infusion of 5 mg. The calculated absorption was 92%. The time course of the plasma levels appeared to follow first order kinetics with an apparent half life of 3.6 (oral) and 3.1 (i.v.) hours. The cumulative urinary excretion att=∞ was 36.1% and 39.2% of the dose administered, respectively, indicating extensive metabolism of the drug. The distribution volume was 136 l. Peak plasma levels were found 80 min after oral administration and they showed up to 4-fold variation after identical doses. Renal clearance was 216 ml×min−1 and total clearance was 483 ml×min−1. In plasma 57% of pindolol was bound to protein.
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  • 11
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    European journal of clinical pharmacology 7 (1974), S. 119-124 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; phenytoin ; diphenylhydantoin ; bioavailability ; generic inequivalence ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels of phenytoin (diphenylhydantoin, DPH) in epileptic patients were significantly higher after treatment with either of two preparations containing the sodium salt of DPH, than after treatment with the same dose of the free acid. This was confirmed in both short and long term studies, and in the latter increased plasma levels of DPH were accompanied by better control of generalized seizures. The degree of acute side-effects in 6 out of 10 patients whose treatment was changed from DPH-acid to DPH-sodium was proportional to the plasma level of DPH; the latter varied from 22.8 to 34.9 µg/ml in affected patients. After a single oral dose in healthy volunteers, the sodium salt of DPH showed much better bioavailability than the free acid. The differences in bioavailability in patients and volunteers probably depended on differences in particle size in the preparations of the sodium salt of DPH and its free acid. The excipient, lactose or starch, did not seem to affect the bioavailability of the two formulations of sodium-DPH.
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  • 12
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    European journal of clinical pharmacology 7 (1974), S. 217-225 
    ISSN: 1432-1041
    Keywords: Rifampicin ; p-aminosalicylic acid ; drug interaction ; isoniazid ; pharmacokinetics ; antituberculous therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of rifampicin (10 mg/kg body weight), p-aminosalicylic acid (0.2 g/kg), isoniazid (10 mg/kg), or rifampicin and either p-aminosalicylic acid or isoniazid, were given to 69 tuberculous patients with normal renal and hepatic function. Ten-fold interindividual differences were observed in the peak serum concentrations and half-lives of rifampicin; its half-life was reduced from 4.3 h after the first dose to 3.1 h after the third dose, possibly due to self-induction of its own metabolism. No effect on its serum concentration or half-life, nor on those of isoniazid, were found after simultaneous oral administration of the two drugs. After treatment with rifampicin and p-aminosalicylic acid, the peak serum level of the former was delayed from 2 to 4 h, it was reduced from 8.0 to 3.8 µg/ml, and the mean area under the serum concentration curve throughout the entire 8 h study period was also lowered by about half. Individual patients did not attain therapeutically effective peak serum concentrations of rifampicin if also treated withp-aminosalicylic acid. The interaction observed between the two drugs is probably due to impaired gastrointestinal absorption of rifampicin, either by alteration of its physico-chemical properties or by a decrease in the gastric emptying rate combined with more rapid intestinal transit. The combination of these two drugs is unsuitable for the routine chemotherapy of tuberculosis.
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  • 13
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    European journal of clinical pharmacology 7 (1974), S. 249-252 
    ISSN: 1432-1041
    Keywords: Practolol ; renal failure ; uraemia ; beta-blockade ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of renal failure on the excretion of oral doses of practolol has been studied. The plasma half-life increased up to 6.6 times normal and the cumulative urinary excretion of the drug was reduced. There was a linear correlation between the overall elimination rate constant of practolol and inulin and creatinine clearances. A linear correlation was also found between the renal clearances of practolol and inulin. The dose of practolol required for maintenance therapy should be reduced in patients with impaired renal function.
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  • 14
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    Cell & tissue research 149 (1974), S. 205-221 
    ISSN: 1432-0878
    Keywords: Locus coeruleus ; Tegmentum ; Mesencephalon ; Adrenergic centers ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The locus coeruleus of cat is populated by two types of neurons: medium sized ones, with plump cell bodies and relatively short dendrites; and small ones, with triangular bodies and relatively long dendrites. The former type is regarded here as typical of the centre, whereas the second type could simply represent displaced neurons from the adjacent griseum centrale. Electron microscopy failed to reveal any outstanding richness in pigment granules in kittens up to five weeks old. Very characteristic somatic appendages were found, mostly in the medium sized neurons. These somatic “spines” communicate with the perikaryon by means of a narrow neck region. A complex, multilayered, glial sheath surrounds the cells. This glial sheath is pierced by the somatic appendages, which are not surrounded by glia and make contact with axonal knobs. Typical dendritic spines appear to be absent. Axodendritic synapses are made on medium sized dendritic trunks. By and large, most of the synaptic vesicles present in the centre are of the small, clear-centered type. However, dense core vesicles extremely variegated in size and appearance were found, both in presynaptic and postsynaptic profiles. The possibility that dense core vesicles should be regarded as atypical lysosomes rich in by-products of the metabolism of catecholamines (melanine) has been considered.
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  • 15
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    Cell & tissue research 152 (1974), S. 283-292 
    ISSN: 1432-0878
    Keywords: Sense organ ; Lateral line ; Synapses ; Ambystoma mexicanum ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Lateral line organs in young salamanders of the species Ambystoma mexicanum were investigated with scanning and transmission electron microscopy. They were found to differ from the lateral line organs in adult animals (1) by being lower, having short hair cells and supporting cells, (2) by the hair cells having areas of lateral contact, (3) by the occasional presence, at the edge of the organ, of hair cells at an early developmental stage. Two types of nerve endings are seen: (1) afferent, and (2) less commonly, efferent vesiculated ones. Synaptic bodies have been seen in the cytoplasm without association to afferent synapses.
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  • 16
    ISSN: 1432-0878
    Keywords: Synapses ; Embryo (Xenopus laevis) ; Spinal cord ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rostro-caudal gradient of differentiation found in vertebrate embryos has been utilized to examine the sequence of synaptic junction development in the spinal cord of Xenopus laevis at a late embryonic stage. Uniform samples were taken at various points along the cord of a stage 27 embryo and examined in the electron microscope. The general ultrastructure of the cord demonstrated the rostro-caudal gradient of development. The sequence of synaptic junction development was like that in the cervical region (Hayes and Roberts, 1973). “Membrane-vesicle clusters” and “immature” synaptic junctions were found most caudally followed by synaptic junctions, first with cleft and subsynaptic membrane density, then with only cleft density and finally, most rostrally, with cleft, subsynaptic membrane, and subsynaptic cytoplasmic density. Mature synaptic junctions were found in increasing numbers from the mid to anterior trunk cord and could mediate alternating trunk flexions made by the embryos at this stage of development. “Membrane-vesicle clusters” were found near processes containing irregular vesicles and also near membrane outlines. These may be signs of dendritic growth. “Membrane-vesicle clusters” were also found in varicosities, facing the space around the spinal cord and in nerve fibres peripherally between the skin and myotomes. This suggests an association of early stages in synaptogenesis with axon growth. This and other possible inferences about axon and dendrite growth in relation to synaptogenesis are discussed.
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  • 17
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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 123-148 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; computer program ; NONLIN ; data weighting ; isoniazid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Several important statistical aspects of pharmacokinetic analyses by digital computer are discussed. These include selection of appropriate equations, weighting of data, precision of parameter estimates, comparisons of parameters, analysis of weighted residuals, and criteria useful in the selection of particular models. Data obtained after administration of isoniazid and isonicotinuric acid to man are analyzed to illustrate the usefulness of the discussed methods.
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  • 18
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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 495-509 
    ISSN: 1573-8744
    Keywords: hepatobiliary transport ; rat ; bromphenol blue ; pharmacokinetics ; roles of liver cytoplasmic Y- and Z-binding proteins and T binder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new pharmacokinetic model is proposed to explain the hepatobiliary transport of a nonmetabolized sulfonic acid dye, bromphenol blue, which is actively transported from the bloodstream into bile. This model has the advantage of taking into account the roles of the liver cytoplasmic Y- and Z- binding proteins and T binder.
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  • 19
    ISSN: 1573-8744
    Keywords: digoxin ; pharmacokinetics ; two-compartment model ; three-compartment model ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract An experiment has been carried out in man designed to compare the fit of a two- and a three-compartment pharmacokinetic model to experimentally determined serum digoxin concentration-time data following rapid intravenous injection of 1.0 mg of the drug. Digoxin was administered to five healthy male volunteers, blood samples were withdrawn repetitively over a period of 72 hr, and samples were assayed using a 125 I radioimmunoassay. Appropriate equations describing two- and three-compartment open models were fitted to the experimental data using weighted nonlinear least squares regression analysis. It was demonstrated that the three-compartment fit resulted in a statistically significant reduction in residual error, a marked improvement in the randomness of scatter of the experimental data about the serum digoxin-time curve, and better agreement of the predicted serum concentration-time curve with experimental serum digoxin concentrations. Thus the three-compartment open model is the simplest pharmacokinetic model consistent with the data observed in this experiment.
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  • 20
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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 347-364 
    ISSN: 1573-8744
    Keywords: metoprolol ; β-receptor antagonist ; pharmacokinetics ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of 3H-metoprolol, a new selective β 1-receptor antagonist, have been studied in healthy volunteers by following the plasma concentrations and the urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. The compound was rapidly and completely absorbed after oral administration, and about 40% of the dose reached the systemic circulation. The estimated half-life of the absorption process was 10 min. Metoprolol was extensively distributed to extravascular tissues, with the half-life of the distribution phase close to 12 min. About 95% of the dose was excreted in the urine within 72 hr, mainly in metabolized form. The elimination halflife of the compound was close to 3 hr as was also the half-life of the total metabolites after oral administration. After intravenous administration, the elimination half-life of the metabolites was raised to 5 hr, indicating that the route of administra tion might influence the metabolic pathways of the parent compound.
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  • 21
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    Bulletin of experimental biology and medicine 78 (1974), S. 1150-1152 
    ISSN: 1573-8221
    Keywords: methindione ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The pharmacokinetics of the new anticonvulsant, methindione, carbon-labeled in the carbonyl and N-methyl groups, was studied in experiments on rats. Methindione is quickly absorbed from the gastro-intestinal tract and passes easily through tissue barriers. The highest concentration of methindione in the brain is observed 15–30 min after administration. The metabolism of methindione and its elimination from the tissues take place rapidly. In most tissues only 6–23% of its maximal concentration still remains after administration of the drug. Metabolites of methindione, labeled in the carbonyl group, are excreted mainly through the kidneys, but metabolites labeled in the N-methyl group are excreted chiefly through the lungs.
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  • 22
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    Bulletin of experimental biology and medicine 78 (1974), S. 1379-1381 
    ISSN: 1573-8221
    Keywords: fluorouracil ; pharmacokinetics ; radiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The dynamics of the concentration of radioactivity in the blood serum, organs, and urine was investigated after intravenous injection of 5-fluorouracil-2-C14 into rats. The preparation is rapidly absorbed from the blood into the tissues in which it accumulates rapidly in high concentrations and it is excreted quickly from the body. The half-elimination period of 5-fluorouracil in the blood is 15 min. It is excreted chiefly by extrarenal routes.
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  • 23
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    European journal of clinical pharmacology 5 (1973), S. 174-180 
    ISSN: 1432-1041
    Keywords: Tricyclic antidepressant ; nortriptyline ; metabolism ; urine ; pharmacokinetics ; twins ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion of nortriptyline (NT) and five of its metabolites was studied by quantitative gas chromatography in 22 twins and 7 unrelated healthy subjects after single (1 mg/kg) and multiple oral doses (0.4 mg/kg t.i.d.) of NT hydrochloride. A mean recovery of 62% of the dose was found after both single and multiple doses. The metabolite pattern in the urine was qualitatively and quantitatively identical in the two regimes, but there were marked variations in the pattern of metabolites between individuals. The disappearance rate of NT from the plasma was mainly determined by the metabolism of NT to 10-hydroxynortriptyline, which varied considerably between individuals. The data suggest that in certain rapid NT metabolizers, the upper limit for the overall clearance of NT from the plasma (if extrahepatic metabolism is assumed to be negligible) might be set by the blood flow through the liver.
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  • 24
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    European journal of clinical pharmacology 6 (1973), S. 268-270 
    ISSN: 1432-1041
    Keywords: Diphenhydramine ; orphenadrine ; gas-liquid chromatography ; N-selective detector ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of nanogram quantities of diphenhydramine and orphenadrine in human plasma. The procedure employs gas-liquid chromatography and a high sensitivity nitrogen detector. It has been used to assay diphenhydramine in plasma after oral administration of therapeutic doses.
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  • 25
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    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of phenobarbital were measured in 18 newborn infants for one to two weeks after birth. The drug had been administered prenatally to the mothers as part of treatment for maternal hypertension or toxaemia. The plasma half-life of the drug in the infants (77–404 h) was inversely correlated with the extent of prenatal exposure to it. In three infants a bi-phasic plasma curve was found as there was a sudden change from slow to fast disappearance on the 5th to 7th day of life.
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    European journal of clinical pharmacology 6 (1973), S. 44-53 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; plasma clearance ; gas chromatography — mass spectrometry ; pharmacogenetics ; twins
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five identical (monozygotic) and 6 fraternal (dizygotic) sets of healthy twins between 47 and 53 years of age were given a single oral dose of nortriptyline (NT) hydrochloride 1 mg/kg. The plasma half-life, the apparent volume of distribution, and the plasma clearance of NT were estimated for each subject as well as the urinary excretion rate of conjugated and unconjugated 10-hydroxynortriptyline (10-OH-NT). “Steady-state” plasma levels predicted from the reciprocal single dose plasma clearance rate of NT agreed well with those observed in a previous study of the same twins 2 years previously. In the present study, there was a 5-fold range of the plasma half-lives and 2-fold variation in the apparent volume of distribution of NT (assuming complete availability on oral administration). No correlation was found between the plasma half-life and the apparent volume of distribution. Analysis of variance showed that most of the variability between persons in plasma half-life, apparent volume of distribution and conjugation of 10-OH-NT was genetically determined. The plasma half-life and apparent volume of distribution may contribute independently to the total interindividual variability of the “steady-state” plasma level of NT.
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    European journal of clinical pharmacology 6 (1973), S. 181-186 
    ISSN: 1432-1041
    Keywords: Phenothiazines ; thioridazine ; serum levels ; pharmacokinetics ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The rate of absorption of thioridazine varied greatly in ten healthy volunteers who took 100 mg in the morning after an overnight fast. The peak level in blood was also variable and it was reached 1 1/4 to 4 h after dosing. Maximal concentrations in the blood varied widely from 0.13 µg/ml to 0.52 µg/ml. No relation was found between the weight or sex of the subjects and the pharmacokinetics of the drug. The serum half life of thioridazine in three healthy volunteers was 9, 10 and 10 h respectively. In a group of 22 patients receiving less than 5 mg/kg body weight a day, there was a strong correlation between the dose and the morning or evening concentration of thioridazine in the blood. A positive correlation was also observed between the age of the patient and the serum level in those who received doses of less than 5 mg/kg body weight.
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    European journal of clinical pharmacology 6 (1973), S. 88-92 
    ISSN: 1432-1041
    Keywords: Noradrenaline pools ; 7-3H-noradrenaline ; neuro-effector junction kinetics ; pharmacokinetics ; sympathoadrenergic activity
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A two-compartment model of 73HNA distribution has been developed for studying sympatho-adrenergic activity in intact man. After infusion of 73HNA at constant speed in resting normal subjects, the decay curves of the plasma concentration and urinary excretion of 73HNA were plotted against time. Analysis of the curves yielded constants and indirect indications about noradrenaline exchange processes in the extracellular environment. Complete evaluation of the neuronal pools and of the pathways of biosynthesis and metabolism was impossible, but it seemed likely that 73HNA entered small neuronal pools that underwent rapid exchange with the extracellular environment, a point of some interest in clinical and pharmacologic investigations.
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    European journal of clinical pharmacology 6 (1973), S. 137-140 
    ISSN: 1432-1041
    Keywords: Urography ; Hypaque® ; Urovist® ; pharmacokinetics ; renal failure
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Comparative tests were carried out, using a radioactive tracer method, on the pharmacokinetics of sodium and methylglucamine diatrizoate. A biological model was simulated using an analogue computer; and the rate and elimination constants, the elimination half life, and the ratio of tissue entry to tissue elimination constants were calculated. Over the period of time required for X-ray diagnosis, the two salts of the contrast medium acid which were tested did not alter the pharmacokinetics of the contrast medium itself.
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    European journal of clinical pharmacology 6 (1973), S. 245-250 
    ISSN: 1432-1041
    Keywords: Procaine amide ; N-acetylprocaine amide ; sustained-release ; pharmacokinetics ; ventricular arrhythmia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with acute myocardial infarction were studied during treatment with either a conventional or a new sustained-release preparation of procaine amide in order to compare fluctuations in plasma concentration and urinary excretion of the drug during “steady state” conditions. Procaine amide in plasma was measured by spectrofluorimetry and the urine concentration of it and its major metabolite, N-acetylprocaine amide, by gas chromatography. The average fluctuation of plasma concentrations was 3.5±0.1 µg/ml during treatment with sustained-release tablets (dosage interval 8 h) and 4.2±0.4 µg/ml during treatment with ordinary tablets (dosage interval 4 h), i. e. it was 20% greater during treatment with the conventional preparation. There was no difference between the two preparations in recovery of the drug from urine (sustained-release tablets 85.4±3.0%; and conventional tablets 90.3±5.4%). Thus, the new sustained-release preparation of procaine amide administered 3 times daily produced the same range of plasma levels as the identical dose of conventional tablets given 6 times a day.
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    European journal of clinical pharmacology 6 (1973), S. 261-267 
    ISSN: 1432-1041
    Keywords: Alclofenac ; antiphlogistic ; man ; pharmacokinetics ; dosage regimes ; plasma levels
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one compartment open model has been found to fit plasma concentration data previously obtained in man after single oral doses of alclofenac; the parameters of the model are: $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ abs=1.3±0.7h, $${\text{t}}_{\tfrac{{\text{1}}}{{\text{2}}}} $$ el=3.5±1.2h, Vd/F=17±6. The model has been used successfully to predict steady-state plasma levels of alclofenac after multiple oral doses. One treatment schedule (initial dose 500 mg, maintenance dose 250 mg five times a day) was administered to two volunteers for five days and the plasma levels of alclofenac determined daily. The latter were in good agreement with computer predictions based on the model. It is now possible, therefore, to select the most suitable dosage regimes for this drug.
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  • 32
    ISSN: 1432-0878
    Keywords: Sympathetic ganglion ; Granule-containing cells ; Synapses ; Three-dimensional analysis ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary The surface of 4 granule-containing cells, in a cluster within the rat superior cervical ganglion, was studied by a serial sampling technique for electron microscopy. The result shows that all the 4 cells receive one, or three afferent synaptic boutons from the preganglionic fibers impinging upon their somata, and a somatic efferent synapse exists at two locations on each soma of the 2 of these cells. The postsynaptic element of the efferent synapse is observed to be represented by non-vesiculated and vesiculated segments of dendrites, soma and a possible axon collateral of the adrenergic principal neuron of the ganglion. There is a remarkably constant development of the attachment plaque between the granule-containing cells themselves, representing 1.7–2.3% of surface area for each cell. The surface area exposed to the extracellular space (covered only by a basal lamina) varies from 0.1 to 2.3% of the total perikaryal surface of the 4 cells. A tendency is noted that those cells without efferent synapses possess a more extensive area exposed to extracellular space than those forming somatic efferent synapse to the postganglionic elements.
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    Cell & tissue research 143 (1973), S. 117-133 
    ISSN: 1432-0878
    Keywords: Nervous system ; Ctenophores ; Intra-mesogleal nervous system ; Synapses ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary Ultrastructural evidence is given of the occurrence of nervous elements in the mesoglea of Ctenophores based on the presence of the typical synapses of this phylum. In Beroids, nervous fibers from the ectodermal nerve-net cross the epithelial basal membrane and run through the mesoglea; they are devoid of any ensheathing cell. These neurites build highly differentiated synapses upon the muscles and upon peculiar cells, tentatively named mesenchymal cells. In Cydippids, nerve fibers and nerve cell-bodies have been observed in the mesoglea of the tentacles. The mesogleal core of each tentacle contains mesenchymal cells and a thick strand of neurons and neurites, forming a kind of elongated ganglion. Neurites of either the axial neurones or the epithelial nerve-net neurones form numerous radial nerve strands across the tentacular muscles. Interneural, neuro-muscular and neuro-mesenchymal junctions are very frequent in the tentacle. As far as the organization of the mesoglea is concerned, the Ctenophora thus appear closer to Turbellaria than to Cnidaria.
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    Cell & tissue research 139 (1973), S. 369-396 
    ISSN: 1432-0878
    Keywords: Synapses ; Giant fibres ; Ventral nerve cord ; Lumbricus terrestris L. ; Electron microscopy
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    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die proximalen Kollateralen der dorsalen Riesenfasern des Regenwurms wurden in Serienschnitten vom Soma bis zum Eintritt in die Riesenfaser verfolgt und im Hinblick auf ihre Feinstruktur und ihre synaptischen Kontakte Untersucht. Es finden sich sowohl chemische als auch elektrische Synapsen. Ihre Feinstruktur wird mit der bekannter Synapsen anderer Wirbellosen und Wirbeltiere verglichen. In beiden Riesenfasersystemen kommen efferente chemische Synapsen mit feinen postsynaptischen Verzweigungen vor, die anscheinend von Bauchmark-Motoneuronen stammen. Das Axon der medianen Riesenfaser weist darüber hinaus nur noch eine elektrische Synapse mit den Rieseninterneuronen auf. Demgegenüber erhalten die Kollateralen der lateralen Riesenfasern zahlreiche Afferenzen, die zum Teil als sensorische Fasern der Epidermis, multisegmentale Fasern der Hauptfaserzüge und Rieseninterneurone identifiziert werden konnten. Weitere Afferenzen stammen vermutlich von unisegmentalen Interneuronen her. Beide lateralen Riesenzellaxone bilden außerdem miteinander eine elektrische Chiasma-Synapse mit besonderen Membraneinfaltungen.
    Notes: Summary The proximal collaterals of the dorsal giant fibres of the earthworm were traced through serial sections from the cell bodies to the giant axons. Their structure and synaptic connections were examined. There are chemical as well as electrical synapses. Their fine structure is compared to that of other known invertebrate and vertebrate synapses. Both giant fibre systems have efferent chemical connections with thin postsynaptic arborizations which probably belong to ventral cord motoneurons. Moreover the median giant axon is connected by an electrical synapse with the giant interneurons. The lateral giant collaterals on the contrary receive many afferences through chemical synapses which were partly identified as sensory fibers from the epidermis, multisegmental axons from the main fibre bundles or giant interneurones. Other afferences probably come from unisegmental interneurones. In addition both lateral giant axons form an electrical chiasma synapse with special membrane folds.
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    Cell & tissue research 141 (1973), S. 301-317 
    ISSN: 1432-0878
    Keywords: Cnidaria ; Nervous system ; Synapses
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    Topics: Biology , Medicine
    Notes: Summary The nervous system of juvenile and adult Ceriantheopsis americanus has been examined with the electron microscope. The nervous system is exclusively ectodermal, forming a plexus of fibres lying between the epithelium and the muscle layer. The plexus consists of three types of nerve fibre that vary in diameter from 0.1 to 20 μ, and a fourth type of fibre of uncertain nature. The reticulum, previously thought to be the ectodermal nervous system, is redescribed as the peduncles of epithelial supporting cells. Intraneural and neuromuscular synapses are described. About 97% of the interneural are polarized. The unpolarized synapses are a variety not previously described, consisting of a series of polarized zones, for which the name multipolarized synapse is proposed. Structurally, the interneural synapses are more complex than those previously seen in the Cnidaria. Presynaptic projections, periodic cleft densities, and a postsynaptic web are described. By contrast, the neuromuscular synapses bear no membrane specializations. On the basis of observed synaptic interactions of its components a preliminary model of the functional organization of the nervous system is proposed.
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  • 36
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    Cell & tissue research 137 (1973), S. 223-250 
    ISSN: 1432-0878
    Keywords: Nervous system ; Ctenophores ; Nerve-net, Nervous concentration ; Synapses ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary A subectodermal nerve-net is demonstrated in ten species of Ctenophores by means of either Methylene Blue vital staining or silver impregnation. There is no evidence of subendodermal nerve-net. The ectodermal nerve-net displays a characteristic polygonal pattern which is thought to result from morphogenetic events. Both bipolar and tripolar neurones occur. Three types of concentrations of nervous tissue are described: a) a high accumulation of nervous perikarya at the aboral sensory pole; b) a noticeable densification of the net along the eight meridional ciliary strands of every species, and around the lips of Beroidea; c) in the Cydippids Pleurobrachia and Hormiphora two thick strands of fibers and neurones interconnecting the aboral organ and the tentacles: the tentacular nerves. Ultrastructural evidence is given for the presence of nervous elements under and amidst ectodermal epithelial cells. Three features allow the recognition and characterization of neurites and neurones: a) numerous clear and/or granulated vesicles; b) microtubules in variable amounts; c) frequent and highly differentiated synaptic contacts. The very peculiar arrangement of the presynaptic elements is observed in all the species of Ctenophores so far studied. These synaptic contacts suggest chemical transmission in the nerve-net. On the basis of ultrastructural evidence the author refutes the nervous nature previously attributed to the ciliated cells of the meridional grooves. A parallel is drawn between nervous systems of Cnidaria and Ctenophora.
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    Cell & tissue research 140 (1973), S. 25-37 
    ISSN: 1432-0878
    Keywords: Heart innervation (Turtle) ; Monomamine-containing cells ; Synapses ; Fluorescence and electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Fluorescence and electron microscopy of the turtle heart indicates the presence of monoamine-containing, granulated cells in the wall of venous sinus and near the openings of the aortic trunks. These cells occur in clusters and are always in association with nerve fibers and/or ganglion cells within the turtle heart. Vesiculated axon terminals make a synaptic contact with the cytolemma of the granulated cell which in turn makes a synapse to the processes from the other granulated cell and to the cardiac nerve fibers. The close contact occurs also between the granulated cell process and the smooth muscle cell membrane in the wall of large vessels. The granulated cell has no special relationship to the blood capillaries. The significance of these results is discussed in relation to nervous control of the cardiac activity of the turtle.
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  • 38
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    Cell & tissue research 140 (1973), S. 203-216 
    ISSN: 1432-0878
    Keywords: Synapses ; Development ; Chick embryo ; Cell culture ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The formation and development of synaptic contacts between dissociated chick spinal cord neurons has been investigated. By the 6th day in vitro “immature” profiles with few vesicles were observed. By 14–18 days “mature” types with numerous vesicles were found, indistinguishable from those of newly hatched chick spinal cord. After this period degeneration occurred, and was especially marked in the post-synaptic element. Such degeneration could be postponed by the addition of small numbers of somatic muscle cells. The Kanaseki and Kadota (1969) technique was applied to the study of coated vesicles at various stages of synaptic development.
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  • 39
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 51-68 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; cell kinetics ; mathematical model ; cell cycle specific drugs
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Predictive models have been developed to simulate cancer cell populations under treatment with cytotoxic drugs, with both direct-acting and cell cycle specific drugs being considered. Models of cell growth kinetics have been combined with simple pharmacokinetic models to complete the cell-drug interaction system. The models depend on knowing the distribution of generation time in the cell population, the cell-drug interaction, and the local concentration of the drug at the effective site. All of the quantities can be obtained, in principle, from separate experiments and combined to form a model describing several aspects of the cell-drug response system.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 497-520 
    ISSN: 1573-8744
    Keywords: tissue distribution ; plasma protein binding ; tissue protein binding ; fat/water partition coefficient ; volumes of distribution ; corticosterone ; pharmacokinetics
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The concentration of a drug at its site of action will be affected by the ability of the drug to distribute to and pass through various membranes and tissues. Mechanisms of drug distribution are summarized in this paper and include the differences between intracellular and extracellular pH,active transport systems for drugs, distribution of drugs between fat and water in adipose tissues, the reversible binding of drugs to phospholipids and to various macromolecules including proteins, nucleic acid, and melanin. These mechanisms usually tend to decrease the concentration of unbound drugs at their sites of action, but usually not to the extent one would predict on the basis of in vitrobinding studies. The effects of drug distribution in altering the biological half-lives of drugs in the body are discussed as well as the interrelationship between the kinetic volumes of distribution for drugs and blood flow rates through the organs that eliminate these drugs. These concepts are illustrated for corticosterone levels following intravenous bolus injections and infusions into rats.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 341-361 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacokinetic models ; bioavailability ; clinical metabolic profile ; chronic dosing regimens
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The present status of pharmacokinetics is reviewed. Pharmacokinetic models and the basic concepts involved in applying models to blood, urine, bile, and tissue levels of drugs and metabolites are discussed. An outline of methods for pharmacokinetic analyses is proposed. Special emphasis is given to the determination of bioavailability of a drug from various dosage forms. Uses of pharmaco-kinetics in determining sites of drug action and in determining a clinical metabolic profile are suggested. The perturbations of magnitudes of pharmacokinetic parameters among individuals challenged with the drug can be used as a diagnostic tool in evaluating the state of dynamic processes, the presence of metabolic diseases and genetic abnormalities, and the failure of physiological functions. The use of pharmacokinetics and the prediction of chronic dosing regimens are reviewed. Typical curves depicting predicted blood levels on repetitive dosing are presented.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 521-540 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; polygenically controlled disease states ; pharmacokinetic twin studies ; pharmacokinetic heritability ; ethanol ; antipyrine ; phenylbutazone ; bishydroxycoumarin.
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of pharmacokinetics to the elucidation of polygenic factors involved in drug disposition is discussed in the context of three questions: (a)How extensive is the variation among individuals in rate of plasma clearance for commonly used drugs? (b)If appreciable variation occurs, what are the relative contributions of genetic and environmental factors to its maintenance? (c) What role is played by polygenic factors in maintaining this variation?Large variance in plasma decay rates for phenylbutazone, ethyl biscoumacetate, antipyrine, isoniazid, and nortriptyline is noted throughout the general population. However, these large variations appear to be controlled predominately by genetic rather than by environmental factors on the basis of studies run on identical and fraternal twins. At the present time, an individual's capacity to metabolize drugs and the effects of various conditions in altering that basal, genetically determined capacity seem to be best indicated by measurements of the plasma antipyrine half-life. While the theoretical advantages of obtaining blood concentrations of drugs as a guide to their more rational administration are evident, several practical problems are discussed in this paper.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 137-163 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; nonlinear regression ; drug distribution ; compartmental models ; computer program ; BASIC ; time sharing ; spectinomycin ; naloxone
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    Topics: Chemistry and Pharmacology
    Notes: Abstract COMPT, a computer program for optimizing the solution of integral compartmental models of drug distribution by nonlinear regression analysis, is written in extended BASIC for use in time-sharing computer systems. It is based on Hartley's modification of the Gauss-Newton gradient method. The characteristics and features of the program are indicated, and the program source listing is presented. This version of COMPT is designed to solve the two-compartment open model of intravenous drug administration. Examples of the results of the operational program are presented. The program is modifiable to permit analytical solutions for other types of systems described by nonlinear equations.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 175-200 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; pharmacodynamics ; cell kinetics ; vincristine ; vinblastine ; arabinosylcytosine ; cyclophosphamide
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacodynamic model is proposed and equations are developed for the quantitative analysis of dose-time-cell-survival curves produced by the administration of cell-cycle-specific chemo-therapeutic agents. The essential feature of the model is an irreversible, bimolecular mechanism of drug-receptor interaction which serves as the interface between the pharmacokinetics of the drug and the cell-cycle-cell-proliferation kinetics of the normal and neoplastic cells. A preliminary cell system which allows adequate characterization of the experimental data is a two-compartment model where cells are assumed to exist in their proliferative and nonproliferative phases. The chemotherapeutic model was used to analyze dose-time-cell-survival curves found in the literature for the effects of vincristine, vinblastine, arabinosylcytosine, and cyclophosphamide on lymphoma and hematopoietic cells in the mouse femur. Similarity in the values of the “cell-kill” constants for these drugs on the two cell types indicates that, in the cell systems studied, the proliferative state of the cells is the primary in vivodeterminant of selective chemotherapy.
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    Keywords: absorption ; amphetamine ; bioavailability ; elimination ; pharmacokinetics ; phentermine ; resin-bound drugs
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma levels of amphetamine and phentermine have been measured in man in a crossover study of the pharmacokinetics of these agents following oral administration of resin-bound and soluble salt formulations. The one-compartment open model with first-order drug absorption was fitted to the data from each subject by nonlinear regression methods and provided an excellent fit. Relative bioavailability of the two salts did not differ for either drug. In both cases the rate constant for absorption was significantly lower and less variable for the resinated compound.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 295-305 
    ISSN: 1573-8744
    Keywords: diazoxide ; pharmacokinetics ; stable-isotope dilution ; GC-mass fragmentography ; solubility ; excretion
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A specific, sensitive, and accurate assay for diazoxide in human plasma and urine samples was developed utilizing stable-isotope dilution-GC-mass fragmentography. 3-Trideuterodiazoxide (d 3-diazoxide) served as internal standard, and diazoxide was N-methylated with diazomethane prior to GC. Plasma elimination half-lives of diazoxide ranged within 20–53 hr in four severely hypertensive patients, which did not correlate with endogenous plasma creatinine levels. A rapid infusion over 10–15 sec of an antihypertensive dose presumably resulted in a very transient precipitation of diazoxide due to its limited solubility of approximately 380 Μg/ml plasma. Urinary excretion accounted for 4–6% of the dose within 24 hr after administration in the four patients studied and totalled 19% and 22% in two patients. Renal clearance of diazoxide was below 1 ml/min on the first day following administration and increased to 2–3 ml/min on consecutive days. It was concluded that renal excretion of diazoxide is self-limited by antihypertensive doses in severely hypertensive patients. The major route of elimination in these patients may be due to metabolism.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 89-98 
    ISSN: 1573-8744
    Keywords: clindamycin ; clindamycin-2-palmitate ; clindamycin-2-hexadecylcarbonate ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology
    Notes: Abstract To determine the bioavailability of clindamycin from the microbiologically inactive clindamycin-2-palmitate and clindamycin-2-hexadecylcarbonate in man, a three-way crossover study was conducted with oral administration of the two esters and clindamycin hydrochloride. In each case, serum clindamycin bioactivity concentrations were fitted to a one-compartment open model with an initial lag time. Analysis of variance of measured quantities (serum concentrations and urinary excretion) and of derived pharmacokinetic parameters showed that for every comparison except maximum serum concentrations clindamycin-2-palmitate was not significantly different (at p=0.05) from clindamycin hydrochloride. Clindamycin-2-hexadecylcarbonate gave significantly different values from those for the hydrochloride in all cases except the rate constant and half-life for elimination from the serum. The palmitate was the superior ester and was bioequivalent to the hydrochloride in man.
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    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Keywords: alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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    European journal of clinical pharmacology 5 (1972), S. 58-61 
    ISSN: 1432-1041
    Keywords: Pralidoxime chloride ; pharmacokinetics ; anti-cholinesterase poisoning
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose of 1.0 g (10.0–14.0 mg/kg body weight) of pralidoxime mixed with various cholinolytics was given by i.m. injection to 29 healthy male subjects. A concentration of pralidoxime in blood of 4 µg/ml was reached after 5 to 10 min with all the mixtures and was maintained for about 1 to 2 h. The calculated half lives of pralidoxime in three groups of subjects were 62.2, 60.0 and 61.8 min., respectively. — The urinary excretions of pralidoxime during the first 4 h after the injections averaged 75.0, 79.6 and 69.6 per cent, respectively, of the total amount given. — The results are compared with published information about similar oximes.
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    European journal of clinical pharmacology 4 (1972), S. 233-240 
    ISSN: 1432-1041
    Keywords: Sulphamethoxazole ; trimethoprim ; pharmacokinetics ; uraemia ; sulphonamides
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulphamethoxazole (SMZ) and trimethoprim (TMP) have been investigated in four healthy volunteers, 15 patients with stable chronic renal failure and 3 patients on regular dialysis. The dosage schedule was 400 mg of SMZ and 80 mg of TMP orally every 12 h. The plasma concentrations and urinary excretion have been analysed in terms of a one compartment open model, allowing for elimination by renal excretion and metabolic processes. — At equilibrium the plasma concentrations of unchanged sulphonamide showed no significant correlation with the degree of renal impairment. The accumulation of TMP increased slightly without affecting the concentration ratio of both agents in plasma. In contrast, increasing accumulation of metabolized SMZ was demonstrated in the presence of renal insufficiency. Indirect evidence indicates that rising metabolite levels under these circumstances may lead to a displacement of unchanged sulphonamide from protein binding sites. — The cumulative urinary excretion amounted to 82.4% of the dose of sulphonamide administered, which probably corresponds to the fraction of the compound absorbed. The urinary concentration of biologically active SMZ was slightly below the plasma level, especially in advanced renal failure, but it remained above the minimum inhibitory concentrations reported in the literature. The concentration of TMP in urine was considerably higher than in plasma, it decreased with loss of renal function as did active SMZ.
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  • 51
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    European journal of clinical pharmacology 4 (1972), S. 191-195 
    ISSN: 1432-1041
    Keywords: Amobarbital ; pentobarbital ; barbiturates ; gas chromatography ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gas chromatographic methods are described for the assay of amobarbital and pentobarbital in 500 µl samples of plasma, in concentrations down to 250 ng/ml. After ether extraction at pH 5.5, the barbiturates are reextracted into an alkaline solution of trimethylanilinium hydroxide and are determined quantitatively by gas chromatography as their dimethylated derivatives. The method has been used successfully in volunteers receiving therapeutic doses of these bariturates.
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    European journal of clinical pharmacology 4 (1972), S. 137-141 
    ISSN: 1432-1041
    Keywords: Fentanyl ; pharmacokinetics ; neuroleptanalgesia ; analogue computer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and urinary excretion of3H-fentanyl were studied in 5 human subjects after intravenous injection of this drug. After an initial rapid decline, the plasma level of fentanyl decreased slowly and approximately exponentially. The plasma concentration of metabolites remained almost steady from 1–3 h after injection. More than 60% of the administered radioactivity was excreted through the kidneys within 4 days. Only a small proportion of it was unchanged fentanyl. The rates of fall of plasma concentration and of urinary excretion were slower in man than in rabbits. — The time courses of plasma concentrations and of urinary excretion were simulated on an analogue computer. The results support the assumption that the different time courses of concentrations in man and rabbits are caused by slower metabolism in man. It seems likely that redistribution plays a dominant part in the short duration of action of fentanyl in man.
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    European journal of clinical pharmacology 4 (1972), S. 150-157 
    ISSN: 1432-1041
    Keywords: Antibiotics ; pharmacokinetics ; microbiological assay ; drug control ; neonatal septicaemia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The various steps of a paper disc micromethod for quantitative determination of plasma concentrations of antibiotics is described. Only 10 µl of plasma is needed for a single determination, allowing easy and repeated capillary sampling. Separate assay was attempted of three antibiotics in a mixture (streptomycin, cloxacillin and ampicillin), both by use of selective inhibitors (semicarbazide, penicillinase) in the culture medium and by choosing suitable strains of bacteria. In this way, it was possible to determine streptomycin and cloxacillin separately when all three antibiotics were present simultaneously in the plasma. The assay of ampicillin, however, was always influenced by the presence of even small concentrations of cloxacillin. The 95% confidence intervals of the standard curves for the three antibiotics are presented. — The method is suitable both for pharmacokinetic studies and for routine clinical control of plasma antibiotic levels, even in premature children.
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  • 54
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    Cell & tissue research 127 (1972), S. 240-257 
    ISSN: 1432-0878
    Keywords: Insects ; Brain ; Corpora pedunculata ; α-lobe ; Synapses
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    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Organisation der α-Loben der Pilzkörper im Gehirn von Acheta domesticus L. wird nach licht- und elektronenmikroskopischen Befunden beschrieben. Der säulenartige Faserkomplex des α-Lobus besteht aus Fortsätzen von Pilzkörperzellfasern (intrinsischen Fasern, IF) und pilzkörperfremden Fasern (extrinsischen Fasern, EF), die in den Lobus eindringen. Die feinen IF durchziehen den Lobus hauptsächlich parallel zu seiner Längsachse, während die EF zumeist senkrecht zur Längsachse angeordnet sind. Der Lobus erscheint von seiner Peripherie bis zu seinem Zentrum durch IF-Zonen gegliedert. Die Verteilung der EF weist auf eine zusätzliche Ordnung von der Basis zur Spitze des Lobus hin. Zahlreiche polarisierte Synapsen verbinden IF mit EF. Die IF zeigen Vesikelanhäufungen und präsynaptische Apparate besonders in Erweiterungen, die auch in Golgi-Präparaten lichtmikroskopisch zu sehen sind. Es werden zwei EF-Typen unterschieden: 1. Postsynaptische EF (zahlreich) und 2. EF mit prä- und postsynaptischen Kontakten, die nur in einigen Regionen des α-Lobus gefunden wurden. Präsynaptische IF konvergieren auf „dendritische“ EF, die Verbindungen mit anderen Teilen des Hirns und des Nervensystems herstellen. Funktionelle Gesichtspunkte werden diskutiert.
    Notes: Summary The organization of the α-lobes of the corpora pedunculata in the brain of the cricket Acheta domesticus L. has been investigated in the light and electron microscopes. The cylindrical fibre complex is composed of branches of “mushroom-body” fibres (intrinsic fibres) and extrinsic fibres, which penetrate the α-lobe. Intrinsic fibres (IF) run through the α-lobe in the same direction, but not strictly parallel to each other or to the axis of the α-lobe. Extrinsic fibres (EF) and their fine branches are often arranged perpendicular to the axis of the α-lobe. There is some evidence that different IF zones occur in the α-lobe when passing from its periphery to its centre. The distribution of EF may reflect a structural order when passing from the base of the lobe to its top. Numerous polarized synapses connect the IF with the EF. The IF show clusters of vesicles and presynaptic figures especially in their “blebs”, which can be seen in Golgi preparations for light microscopy. Two types of EF are distinguished on the basis of their synaptic junctions: (1) postsynaptic EF (abundant) and (2) EF with pre- and postsynaptic sites (perhaps restricted to some regions of the α-lobe). Presynaptic IF converge on EF, which may transfer excitation from the α-lobe to different parts of the brain and nervous system.
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  • 55
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    Keywords: Synapses ; Crustacea ; Abdominal Ganglia ; Lateral glant fibers ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The abdominal ganglia of the crayfish Astacus pallipes contain numerous vertebrate-like synapses which are characterized by presynaptic vesicles, darkened pre- and post-synaptic membranes, cleft material, and post-synaptic “fuzz”. Such synapses occur throughout the ganglia but are most easily found dorsally, where the neuropile is relatively coarse. The neuropile is far from homogeneous. Regional variations in fiber size, in degree of profile tortuosity, and in kind, magnitude, and distribution of vesicular content result in conspicuous textural variations. The structural polarity of synapses between the lateral giant fibers and other neurons is consistent with known physiological polarity and, hence, validates our criteria for recognition of synapses within the ganglion.
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    Cell & tissue research 125 (1972), S. 415-431 
    ISSN: 1432-0878
    Keywords: Synapses ; Rat ; Cerebral cortex ; Glutaraldehyde/E-PTA ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Synaptic junctions in intact rat cerebral cortex have been examined following glutaraldehyde fixation and phosphotungstic acid (PTA) staining. In the presynaptic ending the network has a hexagonal arrangement, while the dense projections are regularly placed along the presynaptic membrane. Cleft densities occupy the intracleft region. The postsynaptic thickening extends uninterrupted along the length of the junction. Qualitatively, the majority of junctions fall into the ‘discontinuous-continuous’ category, in which the internal coat of the presynaptic membrane together with its associated dense projections is discontinuous along the length of the junction, whereas the postsynaptic thickening is continuous. By contrast, a small number of junctions are ‘continuous-continuous’. In an attempt to analyze the junctions quantitatively, nine indices were measured. Histograms of the size distributions of seven of these appear to be bimodal, and from this it is concluded that two junction populations may be distinguishable on quantitative grounds. It is also shown that the distance separating dense projections at the presynaptic membrane is of the order of 10–15 nm. This surprisingly low value has consequences for current ideas on the relationship between synaptic vesicles and dense projections, and these are discussed at length.
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    Cell & tissue research 125 (1972), S. 432-447 
    ISSN: 1432-0878
    Keywords: Synaptosomes ; Synapses ; Rat ; Cerebral cortex ; Glutaraldehyde/E-PTA
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    Topics: Biology , Medicine
    Notes: Summary Working with glutaraldehyde fixed, PTA stained rat cerebral cortex, the authors compared the ultrastructural features of synaptosomes with those of intact synaptic junctions. In general there is close correspondence between the two, although the cleft densities and postsynaptic focal densities of synaptosomes show a greater degree of focalization than their counterparts in synaptic junctions. The dense projections have similar profiles in both preparations, but are more difficult to distinguish clearly in synaptosomes on account of the closer packing of the presynaptic network around their apices. The limiting membrane of the presynaptic terminal is usually visible in synaptosomes, but not in synaptic junctions. Comparing the preparations quantitatively reinforces the qualitative findings, and points to their overall similarity. However a number of the indices in synaptosomes are significantly smaller than the corresponding ones in synaptic junctions, and this points to the operation of a shrinkage factor during fractionation procedures. This is confined to the pre- and post-synaptic components and does not affect the intervening contact region. Histograms of the size distributions of the indices are similar to those obtained for intact synaptic junctions, the majority displaying two peaks. It is concluded that synaptosomes accurately reproduce the major ultrastructural features of synaptic junctions.
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    Cell & tissue research 127 (1972), S. 189-200 
    ISSN: 1432-0878
    Keywords: Crustacean ; Muscle ; Nerve ; Blood vessel ; Synapses
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    Topics: Biology , Medicine
    Notes: Summary Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were employed to study the innervation and vascular supply of crayfish skeletal muscle. Blood vessels and nerve terminals identified by TEM were often closely associated. Synaptic regions of the nerve terminals were always located under sarcolemma and contained both dense-cored and agranular synaptic vesicles. Axo-axonal synapses of several different types were observed. Blood vessels consisted of several “vessel cells” or “supporting cells” enclosing a lumen, which was connected to the exterior by fine channels between the “supporting cells”. SEM of whole freeze-dried muscles revealed two types of ramifying structure, which often ran in parallel over the muscle surface. One, identified as nerve, was more cylindrical and had a smoother surface than the other, which was identified as blood vessel. Fine nerve branches disappeared under the sarcolemma, probably near synaptic regions, but synapses could not be seen. Blood vessels also had fine terminations which merged into the sarcolemma.
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    Cell & tissue research 130 (1972), S. 362-377 
    ISSN: 1432-0878
    Keywords: Lorenzinian ampullae ; Polyodon spathula ; Sensory epithelium ; Synapses ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Light and electron microscopic observations on the ampullary organs of Polyodon spathula (Chondrostei, Osteichthyes) reveal a sensory epithelium similar to that found in the Lorenzinian ampulla, an electroreceptor found in marine Elasmobranchs. The sensory cells have a very small luminal part provided with a cilium. They are innervated by many nerve endings. Each nerve fibre apparently makes synaptic contact with several sensory cells. The synaptic structure in the sensory cell is composed of a flat sheet, the outermost part of which is surrounded by 3 or 4 annuli of densely staining material. The sheet extends into a protrusion of the sensory cell, and there is a corresponding invagination in the nerve terminal. The conclusion that these organs are electroreceptors, is supported by the finding that the fish responds to the introduction of an iron tube in the aquarium, whereas a wooden rod introduced in the same way causes no response.
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    Cell & tissue research 130 (1972), S. 481-488 
    ISSN: 1432-0878
    Keywords: Limulus heart ; Neurogenic heart ; Neuromuscular junctions ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural characteristics of the neuromuscular junctions were studied in the neurogenic heart of Limulus polyphemus. Several types were encountered. The first type consisted of nerve terminals which synapsed along the borders of the myocardial fibers, embedded just under the sarcolemma. A second type of terminal was ensheathed in glial cells, synapsing on the outer sarcolemmal membrane. The third, and most prevalent type of junction consisted of terminals which synapsed with arms of granular sarcoplasm, remote from the fibrillar portion of the muscle fibers. Junctional complexes of the third type were often observed near intercalated discs and were often formed by several axons synapsing with arms of sarcoplasm from several muscle fibers. The results are discussed in relation to the previously reported electrophysiological characteristics of the neuromuscular junctions.
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    Cell & tissue research 126 (1972), S. 278-296 
    ISSN: 1432-0878
    Keywords: Anura ; Pineal organ ; Synapses ; Acetylcholinesterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung In der Epiphyse von Bombina kommen durch „synaptic ribbons“ gekennzeichnete Synapsen und konventionelle Synapsen vor. Bei den „ribbon“-Synapsen handelt es sich um axodendritische und axosomatische Formen. Die axodendritischen „ribbon“-Synapsen lassen sich aufgrund der Zahl der Dendriten und der „synaptic ribbons“ in 2 Typen gliedern. Es kommen Dendriten vor, die nacheinander in „ribbon“-Synapsen und konventionelle Synapsen einbezogen sind. Neben konventionellen und durch „ribbons“ gekennzeichneten synaptischen Verbindungen finden sich weitere Kontakte zwischen Sinnes- und Nervenzellen und Interrezeptorkontakte, die jedoch beide nicht als echte Synapsen angesprochen werden können. Anhand der Befunde zur Synaptologie werden Probleme der neuronalen Schaltung der Epiphyse diskutiert. Beim Acetylcholinesterase-Nachweis findet sich das Reaktionsprodukt vor allem in den Neuropilzonen der Epiphyse. Eine eindeutige Zuordnung zu Fortsätzen bestimmter Zelltypen ist nicht möglich. Das Ergebnis des Acetylcholinesterase-Nachweises in der Epiphyse wird mit entsprechenden Befunden in anderen Bereichen des ZNS und in der Netzhaut verglichen.
    Notes: Summary Both conventional and ribbon synapses occur in the pineal organ of Bombina. Ribbon synapses are both axodendritic and axosomatic. Two axodendritic types can be distinguished on the basis of the number of dendrites and synaptic ribbons. Both conventional and ribbon synapses can be formed with the same dendrite. Other contacts, which cannot be classified as true synapses, are also found between sensory cells and nerve cells and likewise between sensory cells. The synaptology of the pineal organ permits a discussion of the problems of its neurocircuitry. Products of the acetylcholinesterase reaction occur mainly in the plexiform layer of the pineal organ. It is not possible to correlate the reaction products with definite cell types. The results of the acetylcholinesterase reaction in the pineal is compared with corresponding findings in other parts of the CNS and in the retina of the lateral eyes.
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    European journal of clinical pharmacology 4 (1971), S. 54-58 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; infusion ; plasma expander ; blood level fluctuation ; sulfonamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary A hypothetical pharmacokinetic model is reported which describes the decreasing fluctuations in the blood levels of a sulfonamide during infusion of a plasma expander. Its concentration in the serum increases reciprocally with the amount of plasma expander infused. These procedures can be described by simple equations, and it is possible therefore, to calculate the dose required to maintain a constant blood level during the infusion.
    Notes: Zusammenfassung Es wird über ein hypothetisch-pharmakokinetisches Modell berichtet, welches sich mit der absinkenden Serumkonzentration eines Sulfonamids nach Infusion eines Plasmaexpanders beschäftigt. Die Serumkonzentration fällt reziprok zur infundierten Menge des Plasmaexpanders ab. Die Vorgänge lassen sich durch einfache Gleichungssysteme beschreiben. Es gelingt daher, eine Zusatzdosis zu berechnen, welche den bei Infusionsbeginn bestehenden Plasmaspiegel annähernd konstant erhält.
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    European journal of clinical pharmacology 4 (1971), S. 32-37 
    ISSN: 1432-1041
    Keywords: Glibenclamide ; pharmacokinetics ; metabolism ; potentiation of hypoglycemic action ; phenylbutazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary Metabolically healthy subjects were given an intravenous injection of 1,13 mg14C-labelled glibenclamide (HB 419). The plasma level, renal elimination of the radioactivity and metabolism of the substance were investigated. Two minutes after administration the HB 419 is virtually present only in the blood and at the end of the distribution period mostly in the extracellular space. 53% of the radioactivity is excreted via the kidneys in the form of metabolites. If glibenclamide is administrated in the same way to the same subjects after pretreatment with phenylbutazone there are no differences in the course of the plasma levels or the rate of elimination from the blood. There is, however, a significant difference in the excretion of the radioactivity in the urine. In the presence of phenylbutazone significantly less HB 419 metabolite is excreted renally. In view of the known alternative route of elimination it is suggested that the amount not excreted in the urine is in compensation eliminated via the bile. There was no difference in the metabolism of glibenclamide between the control and phenylbutazone treated groups. The potentiation by phenylbutazone of HB 419 action, and probably also that of other antidiabetic sulphonylureas, must therefore be due predominantly to other causes (Communication III).
    Notes: Zusammenfassung Stoffwechselgesunde Versuchspersonen erhielten14C-markiertes Glibenclamid in einer Dosis von 1.13 mg/Vpn i.v. gespritzt. Plasmaspiegelverläufe, renale Elimination der Radioaktivität und die Metabolisierung der Substanz wurden untersucht. Zwei Minuten nach der Applikation ist HB 419 praktisch nur im Blutund nach Abschluß der Verteilung weitgehend im Extracellulärraum vorhanden. 53% der Radioaktivität werden über die Nieren in Form von Metaboliten ausgeschieden. Wird den gleichen Probanden nach Prämedikation mit Phenylbutazon Glibenclamid in gleicher Weise verabfolgt, ergibt sich kein Unterschied hinsichtlich der Plasmaspiegelverläufe und der Eliminationsgeschwindigkeit aus dem Blut. Ein signifikanter Unterschied besteht jedoch in der Ausscheidung der Radioaktivität in den Harn (26.3%). In Gegenwart von Phenylbutazon wird ein signifikant geringerer Anteil von HB 419-Metaboliten renal eliminiert. Aufgrund des bekannten zweiten Ausscheidungsweges wird vermutet, daß der fehlende Anteil kompensatorisch über die Galle eliminiert wird. Die Metabolisierung von Glibenclamid weist keine Differenzen zwischen Phenylbutazon-und Kontroll-Gruppe auf. Die Wirkungspotenzierung von HB 419 — wahrscheinlich auch diejenige anderer antidiabetisch wirksamer Sulfonylharnstoffe — durch Phenylbutazon dürfte demnach überweigend andere Ursachen haben. (Mitteilung III).
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    European journal of clinical pharmacology 3 (1971), S. 221-228 
    ISSN: 1432-1041
    Keywords: Biguanides ; butylbiguanide ; pharmacokinetics ; sustained release form
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In man, after oral administration of 50 mg14C-butylbiguanide, the maximum serum concentration was 26–41 µg/100 ml. The biguanide was eliminated with an average half-life of 2h. 84% of the dose administered was found excreted unchanged in the urine. — After administration of14C-butylbiguanide in a sustained release form (Silubin® retard), the drug was slowly released and its serum concentration remained almost constant for up to 7 h.
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    Cell & tissue research 115 (1971), S. 494-500 
    ISSN: 1432-0878
    Keywords: Axon ; Synapses ; Astrocytes ; Thalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Electron microscopic studies and three-dimensional graphic reconstructions from serial sections have shown that the large axon terminals of synaptic glomeruli in the ventrobasal nucleus of the rat are invaginated by spine-like protrusions from the astrocyte processes surrounding the glomeruli (“micro-trophospongium”). The astrocytic protrusions are similar in dimensions and internal morphology to the synapse-bearing dendritic excrescences that also invaginate the large axon terminals. Consequently astrocytic protrusions may be overlooked, or confused with dendritic excrescences sectioned at a non-synaptic level. The intimate neuronal—neuroglial relationship at such large axon terminals may reflect ion-exchange or metabolic interactions between the astrocytes and the axon terminal.
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    Cell & tissue research 114 (1971), S. 557-579 
    ISSN: 1432-0878
    Keywords: Retina ; Tissue Culture ; Synapses ; Retinal Rods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Netzhäute von 2–3 Tage alten Ratten wurden in Plasma auf Deckgläsern in Rollerröhrchen zur Kultur angesetzt. Nach 7–17 Tagen in vitro wurden die Kulturen mit Aldehyden und Osmiumsäure fixiert und für elektronenmikroskopische Untersuchung weiterverarbeitet. Gewebsquerschnitte (senkrecht zum Deckglas) zeigten histotypische Organisation, besonders in den dickeren Abschnitten der Explantate. Die Schichtung der Zellen entwickelte sich ganz ähnlich derjenigen in der Retina in situ aus dem relativ primitiven ausgepflanzten Netzhautepithel, jedoch enthielten die verschiedenen Schichten weniger Zellen als in der Retina in vivo. Alle Hauptnervenzelltypen konnten auf Grund ihrer Lokalisation und ihrer cytologischen Merkmale unterschieden werden. Die Entstehung von membranösen Lamellen in den Außengliedern der Sinneszellen konnte als Einfaltung der Plasmamembran beobachtet werden. Synaptische Bandkomplexe in ausgereifter Form wurden in der äußeren plexiformen Schicht nachgewiesen, während konventionelle Synapsen in der inneren plexiformen Schicht häufig angetroffen wurden. Synaptische Bänder waren ebenfalls in den Axonen bipolarer Zellen in der inneren plexiformen Schicht nachweisbar. Amakrine und Ganglienzellen waren in diesen Regionen ziemlich selten vertreten. Da die Untersuchung von nicht kultivierten Netzhäuten drei Tage alter Tiere keinerlei Synapsen zeigte, wird geschlossen, daß die Synapsen in den Kulturen in vitro entstanden sein müssen. Die Netzhaut stellt ein günstiges Modell für die Synaptogenese in vitro dar, indem sie verschiedene Vorzüge vor Explantaten aus anderen Regionen des Zentralnervensystems aufweist, nämlich eine klare Schichtung, zahlreiche identifizierbare Zellfortsätze mit charakteristischen synaptischen Beziehungen und eine wohl definierte Folge von Entwicklungsvorgängen.
    Notes: Summary Retinae from two- and three-day-old rats were explanted in plasma clots and grown in vitro with the flying coverslip method. After seven to seventeen days in culture, the retinal tissue was fixed with aldehydes and osmium tetroxide and embedded for examination with the electron microscope. Study of cross sections (perpendicular to the coverslip) revealed a histotypic pattern of organization, especially in the thicker regions of the explants. Layering of cells quite similar to that in the intact retina was seen to develop from the relatively primitive, explanted retinal epithelium. However, each layer contained fewer cells than its counterpart in vivo. All major neuronal cell types were distinguished by their location and cytological characteristics. Development of the saccules of sensory cell outer segments was observed to occur in vitro by an infolding of the plasma membrane. Synaptic ribbon complexes developed to the mature form in the outer plexiform layers, while conventional synapses were numerous in the inner plexiform layers. Synaptic ribbons were also seen in bipolar cell axons in the inner plexiform layers. Amacrine and ganglion cells in these regions were relatively sparse. A survey of posterior regions of noncultured three-day-old rat retinae showed no synapses of any sort; therefore the synapses in the cultures formed in vitro. The retina is recommended for studies of synaptogenesis in tissue culture, for it offers several advantages over expiants from other areas of the neuraxis, including a clear layering pattern, many identifiable cell processes with characteristic synaptic relationships between them, and a well-defined sequence of developmental events.
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    Cell & tissue research 118 (1971), S. 532-554 
    ISSN: 1432-0878
    Keywords: Glomera coronaria ; Cat ; Chemoreceptor cell ; Blood supply ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Gefäße der zwischen Aorta ascendens und Truncus pulmonalis, an der Vorder- und Hinterwand des Truncus pulmonalis gelegenen Glomera, sowie das sogenannte „Glomus pulmonale“ der Katze lassen sich von den Coronararterien aus durch Tusche-Gelatine-Lösungen füllen. Die erwähnten Paraganglien sind als Chemoreceptorenfelder dem Coronarkreislauf angeschlossen und daher als Glomera coronaria zu bezeichnen. Licht- und elektronenmikroskopische Untersuchungen ergaben eine morphologische Übereinstimmung mit dem Glomus caroticum. Vagusdurchtrennungen verursachen eine Degeneration der an den Glomuszellen gelegenen synaptischen Formationen sowie Veränderungen in Glomuszellen.
    Notes: Summary The vessels of the glomera that lie between the aorta and the pulmonary trunk, on the anterior and posterior wall of the pulmonary trunk, as well as the so-called glomus pulmonale of the cat have been injected with gelatine-india ink mixture. The paraganglia mentioned above are associated with the coronary circulation as chemoreceptors and are designated as the glomera coronaria. The investigations demonstrate a morphologic similarity with the glomus caroticum. Section of the vagus causes a degeneration of the synaptic structures on the glomus cells as well as changes in the cells themselves.
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    Cell & tissue research 113 (1971), S. 396-419 
    ISSN: 1432-0878
    Keywords: Lateral geniculate nucleus ; Synapses ; Interneuron ; Transneuronal degeneration ; Monkey
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    Notes: Summary Two neuron types are distinguished by electron microscopy in the lateral geniculate nucleus (LGN) of the monkey-a large cell (P cell) interpreted as a geniculostriate relay cell, and a small cell (I cell) interpreted as an inhibitory interneuron. The I cell, distinguished by its small size, infolded nucleus, small mitochondria, cilium and small granular bodies, forms about 10% of the total neuron population. It could not be determined whether this cell has an axon, but its dendrites, which contain aggregates of flattened vesicles, are thought to form a proportion of the “F processes”, profiles which are post-synaptic to the retinal (RLP) axons and presynaptic to the dendrites of the P cells. The small dark (RSD) axon terminals of unknown origin contact the dendrites of both cell types. After eye enucleation the P cells of the affected laminae of the LGN shrink and partially withdraw their dendrites from the neuropil. By 29 months' survival, they have only a narrow cytoplasmic rim around the nucleus. A necrotic process also occurs, affecting fine dendrites by 22 days and large profiles by 45 days, but it is not clear whether whole cells are destroyed by this process. At 45 days the I cells are commonly seen to form somatodendritic synapses. The appearance of these synapses is interpreted as the result of a withdrawal to the soma of the presynaptic dendrites. It is concluded that the I cells are probably inhibitory interneurons subject to excitation and presynaptic inhibition by the RLP and RSD axons, and a diagram is presented to demonstrate the possible significance of these connections for the transmission of information through the LGN.
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    Cell & tissue research 116 (1971), S. 564-577 
    ISSN: 1432-0878
    Keywords: Axons ; Dendrites ; Microtubules ; Endoplasmic Reticulum ; Synapses
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    Topics: Biology , Medicine
    Notes: Summary Electron microscopic studies of neural processes in the cerebellum, optic tectum, and cerebral hemisphere of the frog reveal a distinctive system of SER cisternae lying at intervals (commonly 1–2 μm apart) perpendicular to the long axis of axons and dendrites, interconnected by tubular, longitudinally orientated SER elements, and in direct continuity with the outer membrane of mitochondria. The transverse cisternae are fenestrated, with a single mierotubule (or rarely, two) passing through the centre of each 50–75 nm fenestration. Extensions of the SER-microtubule complex may be located parasynaptically in axon terminals and dendrites. The SER of dendritic spines also appears to be continuous with the fenestrated cisternae. Possible roles for the specialized SER (particularly of the parasynaptic extensions), such as calcium ion sequestration and ATP or monoamine oxidase transport, are discussed.
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    European journal of clinical pharmacology 3 (1970), S. 3-11 
    ISSN: 1432-1041
    Keywords: Amphetamine ; drug dependence ; pharmacokinetics ; amphetamine psychosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen subjects with amphetamine psychosis were studied with respect to fluid balance, intensity and duration of psychotic symptoms, urinary and plasma amphetamine levels and the relative amounts of unchanged drug and metabolites in urine. On admission to hospital about half of the psychotic patients were dehydrated, the water lack being up to 6.7% of total body weight. The dehydrated subjects had lower renal clearances of amphetamine because of lower rates of urine production. As noted previously there was a strongly positive correlation between urinary pH and the half life (T 1/2) of plasma amphetamine, with an increase inT 1/2 of about 7 h for every unit increase in urinary pH. Patients with alkaline urine had intense psychoses lasting for about 4 1/2 days after the last dose of amphetamine. In patiens with acid urine, the psychotic symptoms were milder, and of about 2 days duration. No correlation was found between the degree of psychosis in different subjects and the plasma levels of the drug. — The ratio between the amounts of labelled metabolites and unchanged drug excreted in urine rose for each day after administration of3H-amphetamine, implying a slower excretion rate for the metabolites than for the parent drug. The relative proportion of metabolites was higher in patients with an alkaline urine, being more than 90% after the first day. — When amphetamine (200 mg i.v.) was given to nonpsychotic, dependent subjects, the peak plasma levels (mean 423 ng/ml) exceeded the highest levels observed during the first day in psychotic patients. However, no psychotic symptoms were observed in these subjects. The volumes of distribution calculated from the monoexponential elimination curves were higher than those previously reported in nondependent subjects. — With an alkaline urine a group of nonpsychotic amphetamine-dependent subjects had significantly longer plasmaT 1/2 (p〈0.05) than a group of drug-naive control subjects. The results suggest that increased tissue binding may be a component in tolerance to amphetamine in dependent humans.
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    European journal of clinical pharmacology 3 (1970), S. 36-42 
    ISSN: 1432-1041
    Keywords: Sulphonamides ; sylfametopyrazine ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulfametopyrazine were studied for seven days after a single oral dose of 2 g. in healthy volunteers in order to establish its chemotherapeutic value. — The appearance and disappearance of the drug in the plasma were evaluated both for compounds with a free amino group and for total sulphonamides. The half-life and absorption, distribution, elimination and excretion coefficients were calculated, as well as the concentrations in plasma water and interstitial fluid. The estimated drug concentrations in the urine agreed with those calculated from the excretion coefficients. — In all subjects at the end of the seventh day the concentrations in all body compartments of active compounds exceeded the minimum required for a therapeutic effect. The highest concentrations found in the urine were always significantly lower than the drug's basal solubility at pH 5, thus excluding any risk of crystalluria.
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    Cell & tissue research 107 (1970), S. 454-465 
    ISSN: 1432-0878
    Keywords: Cerebellum ; Neuron ; Synapses ; Myelin sheath ; Tissue culture
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    Topics: Biology , Medicine
    Notes: Summary In long-term organized cultures of newborn mouse cerebellum, granule cell neurons were studied with silver impregnation and electron microscopy. In silver impregnated cultures, small neurons are defined as granule cell neurons from their size, morphology and location. There are also occasional large nerve endings with the morphology typical of mossy fiber endings. In correlative electron micrographs, granule cell neurons revealed a faithful reproduction of characteristic structures seen in vivo. The fine structural details of cerebellar glomeruli and myelinated granule cell bodies developed in vitro were also described.
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    Cell & tissue research 107 (1970), S. 508-521 
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    Keywords: Synapses ; Axo-axonal ; Adrenergic and cholinergic terminals ; Ultrastructure
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    Notes: Summary The relations between adrenergic and cholinergic terminals were studied in rat iris and rat heart with the electron microscope. Adrenergic terminals were identified by treating the animals with 5-hydroxydopamine, which produces dense-cored synaptic vesicles in adrenergic terminals in tissues fixed in glutaraldehyde and osmium. The specificity of this observation was verified. It was found that adrenergic and cholinergic nerve terminals often come in close contact with one another, the distance between the adjoining membranes being about 250 Å. At times, faint membrane thickenings could be observed in these places. The available pharmacological, physiological, and morphological evidence leaves little room for doubt that cholinergic terminal fibres can influence the adrenergic fibres. From mainly morphological evidence, it is also postulated that adrenergic terminals influence cholinergic ones.
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    Cell & tissue research 111 (1970), S. 572-585 
    ISSN: 1432-0878
    Keywords: Brain ; Intraventricular cellular processes ; Ependyma ; Lateral ventricle ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Ependym und subependymale Strukturen der Seitenventrikel von Katzen aus dem Bereich des Nucleus caudatus und des Corpus callosum wurden nach Perfusionsfixierung elektronenmikroskopisch untersucht. Dort findet sich eine Reihe von Neuritenanschnitten, deren kolbenförmige Auftreibungen leere Vesikel, “dense core granula” und Mitochondrien enthalten. Neben diesen neuronalen Elementen werden auch Zellfortsätze nichtneuronaler Natur im Ventrikellumen beobachtet, die Ependym- und intraventrikulären Zellen entstammen. An umschriebenen Stellen nehmen diese kolbig aufgetriebenen Fortsätze desmosomenartige Kontakte mit dem Ependym auf. An diesen Orten umgeben Mikrovilli die Fortsätze korbartig. Ob es sich bei diesen Kontakten um synapsenartige Strukturen handelt, oder um „Rezeptoren“ für unbekannte chemische Stoffe, wird diskutiert. Die Kontakte sind unabhängig von der Form der Ependymzellen und davon, ob diesen graue oder weiße Substanz unterliegt. Zwischen und in den Ependymzellen finden sich — bedingt durch den unterschiedlichen Gehalt an Zellorganellen — drei verschiedene Arten von Fortsätzen. Die Zahl der neuronalen Fortsätze in diesem Bereich ist sehr viel kleiner als im Ventrikellumen.
    Notes: Summary Ependyma and subependymal regions of the lateral ventricles of cats (area of Nucleus caudatus and Corpus callosum) were fixed by perfusion and investigated electronmicroscopically. Intraventricular axons showing a beaded shape with smaller and thicker parts were found. The varicosities contain empty vesicles, dense core granules and mitochondria. Beside those certainly neuronal elements there exist intraventricular cell processes originating from ependymal cells and free cells. The neuronal processes make desmosome-like contacts with the ependyma. These regions of contact are surrounded by basket-like arranged microvilli. It is discussed, whether the contacts function like synapses or as receptors for a substance, which is still unknown. Contacts do not depend on the shape of ependymal cells. They exist with the ependyma of Nucleus caudatus (grey substance) as well as with the ependyma of Corpus callosum (white substance). Because of the different contents of cell-organelles one can differentiate three different sorts of processes situated inter- or intracellularly in the ependyma. Neuronal processes within the lateral ventricles are more numerous than those found within the ependymal layer.
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    Cell & tissue research 111 (1970), S. 179-194 
    ISSN: 1432-0878
    Keywords: Synaptosomes ; Rat cerebral cortex ; Synapses ; Postnatal development
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    Topics: Biology , Medicine
    Notes: Summary Synaptosomes (nerve-ending particles) prepared from the cerebral cortex of rats, aged 2–21 days, were examined after fixation in glutaraldehyde and osmium tetroxide, in order to study the development of the contact region between their pre- and postsynaptic components. Synaptosomes were present at all ages studied, although they increased in number and underwent morphological changes, e.g. a decrease in ribosomes and increase in synaptic vesicles, during development. The seventh postnatal day appeared to be a critical period for development, as many adult features were first observed at this time. The synaptic contact region was characterized by desmosome-like symmetrical thickenings until the fourth postnatal day, after which it became increasingly asymmetrical. The postsynaptic thickening, which had been undifferentiated until the seventh day, underwent a focalization of its material at this stage to form postsynaptic densities typical of the adult synapse. Cleft material was present at all ages, although for the first few days it was sparse and comparatively unorganized. An attempt has been made to distinguish between synaptosomes derived from axosomatic and axodendritic endings. The possible significance of the early desmosome-like thickenings is discussed, and the role of the cleft material and post-synaptic densities in the development of the synapse is analysed.
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    Cell & tissue research 110 (1970), S. 540-558 
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    Keywords: Cerebral cortex ; Synapses ; Rat ; Postnatal differentiation ; Morphology
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    Notes: Summary The ultrastructure of layers I and II of the motor cerebral cortex of rat brain has been studied at birth, 4, 7 and 14 days postnatal and in the adult. Compared with the adult, neonatal rat motor cortex exhibited a large extracellular space which decreases with increasing age. At all stages studied the neurons were seen to contain the organelles usually found in adult neurons. Growth cones were present in decreasing numbers up to 14 days old. Synapses were detectable at birth and there was an obvious increase in their number throughout the postnatal development. At the earliest stages studied there was a lack of specialization characteristic of the adult. Many synapses were either avesicular or relatively so and lacked the high degree of modification of adult pre- and postsynaptic membranes. By 7 days after birth many synapses existed which in all morphological respects resembled those of the adult, and by 14 days, the majority were of the adult type. These findings, particularly with reference to the postnatal development of synapses, have been discussed in relation to the known electrophysiological findings.
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    Cell & tissue research 108 (1970), S. 282-296 
    ISSN: 1432-0878
    Keywords: Synapses ; Complex ; Nuclei vestibulares ; Lampetra planeri
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    Topics: Biology , Medicine
    Notes: Summary The vestibular fibres of ammocoetes of Lampetra planeri form a peculiar type of synaptic contact with the large nerve cells of the vestibular nuclei. In fact, a large expansion of the fibre is enveloped by the nerve cell cytoplasm, which makes a sort of spoon or actual channel by sealing its own plasma membrane with adhesion plaques around the fibre. In the whole area of juxtapposition between the fibre and the cell membranes, three different types of specialized contacts occur: desmosomoid junctions, which are the most numerous; zones having the characteristics of chemically active synapses on account of the presence of vesicles clustered on the presynaptic side; gap-junctions, where electrical transmission might occur. A puzzling feature is the presence of an enormous number of presynaptic vesicles located in the central part of the axoplasm of the fibre expansion.
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    Cell & tissue research 108 (1970), S. 563-581 
    ISSN: 1432-0878
    Keywords: Insect ; Brain ; Deutocerebrum ; Synapses
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    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Feinstruktur des Glomerulineuropils im Antennenhügel (sensorisches Zentrum) der Wanderheuschrecke Locusta migratoria wird beschrieben. Die Glomeruli stellen ein kompliziertes Netzwerk von sensorischen Antennennervenfasern und interneuronalen hirneigenen Elementen dar. Die Nervenfasern sind in ihrer großen Mehrheit von klaren synaptischen Vesikeln gefüllt, die sich mit Zinkjodid-Osmiumsäure färben (Akert und Sandri, 1968). Zwei Synapsentypen treten auf, die sich vor allem durch die Form und Ausdehnung des Synapsenspaltes unterscheiden. Beide Typen zeigen eine morphologische Polarität. Paramembranöses synaptisches Material läßt sich besonders deutlich mit der Wismutjodid-Methode von Pfenninger et al. (1969) darstellen. Diese Methode, die den gleichen Effekt wie bei Wirbeltieren zeigt, scheint zur Beurteilung synaptischer Verhältnisse (Verteilung, Häufigkeit) besonders geeignet. Normalerweise sind über synaptische Kontakte drei aneinandergrenzende Nervenfasern miteinander verknüpft. Obwohl Degenerationsexperimente vorgenommen wurden, konnte die synaptische Verschaltung der verschiedenen Fasern nur teilweise geklärt werden. Sensorische Fasern sind mit interneuronalen Fortsätzen verbunden, die prä- und postsynaptische Zonen haben. Es gibt einige Hinweise, daß auch sensorische Fasern miteinander synaptisch verknüpft sind. Vesikelfreie postsynaptische Elemente sind sehr selten, während eine synaptische Verbindung über „axo-axonale“ Kontakte häufig vorkommt. Die Antennalglomeruli mit ihrer großen Anzahl von kleinen, mit synaptischen Vesikeln gefüllten Fasern sind deutlich anders organisiert als die Glomeruli im Pilzkörperkelch (vgl. Lamparter et al., 1969).
    Notes: Summary The fibre anatomy of the glomeruli neuropil of the antennal lobes (sensory centres) of Locusta migratoria has been analysed by electron microscopy. The glomeruli consist of interneuronal and sensory elements of the antennal nerve, forming a complicated mesh-work of fine fibres. The great majority of nervous fibres is filled with clear synaptic vesicles, which stain with zinc-iodide-osmic-acid (Akert and Sandri, 1968), Two types of synaptic junctions are found, differing especially in shape and size of their synaptic gap. Both types show a clear morphological polarity, so that the distinction of pre- and postsynaptic fibres is possible. Inter- and intracellular paramembraneous synaptic material can be demonstrated by the bismuth iodide impregnation of Pfenninger et al. (1969) This method, showing the same effect as in vertebrate nervous systems, seems to be very adequate for the identification of synaptic structures and synaptic distribution. Normally presynaptic structures are situated in angles of nerve fibres. Although degeneration experiments were made, the synaptic interaction of the various fibre types could only partially be explained. Sensory fibres interact with intemeurons, which show pre- and postsynaptic zones. They seem to be responsible for the integration of different glomeruli. There is some evidence that sensory fibres have synaptic connections, too. Postsynaptic profiles with several synaptic contacts and free of vesicles are very rare, whereas “axo-axonic” contacts are found quite often. These glomeruli with their great number of vesicle-filled profiles differ from corpora pedunculata calyx glomeruli (see Lamparter et al. 1969).
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    Cell & tissue research 110 (1970), S. 336-349 
    ISSN: 1432-0878
    Keywords: Nervous system ; Flies ; Intermediate retina (Lamina) ; Centrifugal fiber system ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary By combining the Golgi and the electronmicroscope techniques it has been possible to identify accurately the system of centrifugal fibers which arborizes in the lamina of muscoid flies forming the so-called nervous bags. Each of them originates from a single fiber entering the lamina at the site in which the second order and the long visual fibers leave it. This single fiber represents the peripheral portion of a T-shaped trunk stemming from a small neuronal body located in the external region of the medulla. The central branch terminates within the first synaptic field of this visual center. After entering the lamina the centrifugal fiber ramifies profusely and its branches can be seen climbing and synapsing on the surface of the photoreceptor axon endings. The synaptic loci show characteristic synaptic ribbons located within the nervous bag fibers. This fact suggests that direction of conduction is from the medulla to the lamina. This study has also revealed that the intramedullar terminals of the centrifugal fibers establish intimate contacts with one of the two second order fiber endings.
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    Cell & tissue research 110 (1970), S. 559-568 
    ISSN: 1432-0878
    Keywords: Cerebral cortex ; Rat ; Synapses ; Postnatal ; Quantitation
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    Topics: Biology , Medicine
    Notes: Summary Quantitation of synapses at different postnatal ages has been undertaken in the cerebral cortex of the rat. In this study axial ratios of presynaptic bags, proportion of cortex occupied by presynaptic bags and numbers of synapses per unit volume of cortex have been estimated. Observations on synaptic vesicle packing densities have also been made. Synaptic bags become increasingly spherical up to 7 days of age and become more elongated thereafter. The proportion of cortex occupied by presynaptic bags increases rapidly up to 7 days of age and then at a decelerated rate up to maturity. The number of synapses per unit volume increases slowly over the first four days after which there is a rapid increase to 14 days, followed by a decelerated rate. The average presynaptic bag shows marked changes in volume with increasing age which indicate the probability of two stages of synaptic development. This two stage development is further reflected in the estimates on vesicle packing densities. The implications of the results are discussed in relationship to changes in functional activity of the cortex during postnatal development.
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    Cell & tissue research 111 (1970), S. 195-208 
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    Keywords: Synaptosomes ; Rat cerebral cortex ; Glutaraldehyde/PTA ; Synapses ; Postnatal development
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    Notes: Summary Synaptosomes derived from 2–21 days postnatal rat cerebral cortex have been examined following glutaraldehyde fixation and block PTA staining, with the aim of investigating the maturation of the paramembranous densities at the contact region between the pre- and postsynaptic components. The internal coats of pre- and postsynaptic membranes first appear as undifferentiated plaque-like thickenings, which gradually develop into, or are replaced by, dense projections and postsynaptic focal densities respectively. Both sets of densities pass through an interconnected phase before starting to emerge as discrete entities at 5–7 days. The external coats of the pre- and postsynaptic membranes coalesce to form a plate-like structure which breaks down during development to form the cleft densities or transverse bars of the adult contact region. Although for the first few days of postnatal development only one type of synaptosome can be identified, from 5 days onwards two types corresponding to types A and B of adult life become recognizable. Increase in height of the dense projections has been correlated with increase in the number of synaptic vesicles per synaptosome during postnatal development, indicating that the synaptic vesicles may play a role in the formation and maturation of dense projections. The possible importance of other factors in this process is also discussed.
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    Cell & tissue research 103 (1970), S. 129-148 
    ISSN: 1432-0878
    Keywords: Enteropneusts ; Nerve fibre ; Neurocord ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The nerve fibre layer and the neurocord of the Enteropneusts Saccoglossus horsti, Harrimania kupfferi and Ptychodera flava have been examined with the electron microscope. The nerve fibres vary in diameter between 0.15 to 10 μm. The majority of the fibres are of the smaller diameters. The nerve fibre layer is intraepidermal, and is divided by processes running radially from the epithelial cells to the basement membrane that separates the nerve fibre layer from the muscle cells. The cells of origin of these nerve fibres are situated mainly in the innermost layers of the epidermal cells. The nerve fibre profiles contain numerous vesicles of very varied diameter and contents, together with larger granular inclusions that are also found in the nerve cell bodies. Morphologically recognisable synapses are rare, but the majority of fibres are in intimate contact with one another. Sometimes the mass of fibres is divided into bundles by the epithelial cell processes. The majority of giant fibres are situated near to the basement membrane of the neurocord. The giant fibres also have a varied content of vesicles as well as neurofilaments and neurotubules. The central canal in Ptychodera flava and the remnants of the central canal in Saccoglossus horsti are both lined by columnar cells that bear microvilli as well as cilia with the typical 9 + 2 pattern of tubules. Scattered amongst these cells are mucus secreting cells which open into the cavity of the canal.
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    Cell & tissue research 103 (1970), S. 365-381 
    ISSN: 1432-0878
    Keywords: Insects ; Brain ; Corpora pedunculata ; Mushroom bodies ; Synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung 1. Die Stiele der Corpora pedunculata im Gehirn von Acheta domesticus L. weisen eine Zonierung auf, die auf einer bestimmten Gruppierung von Globulizellfasertypen in der Stielsäule beruht. 2. Pilzkörperfremde Fasern durchziehen das Stielneuropil in allen Richtungen. Sie sind besonders klar zu erkennen, wenn sie senkrecht zu den Globulizellfasern verlaufen. 3. Sog. chemische Synapsen treten hauptsächlich in der Zone III, die den größten Teil des Stielvolumens einnimmt, und im basalen Stiel in der Zone IV auf. Außer synaptischen Vesikeln, die sich mit Zinkjodid-Osmiumsäure imprägnieren lassen, finden sich in den Pilzkörperfasern zahlreiche osmiophile Grana vom Typ der „dense core vesicles“. 4. Globulizellfasern sind mit pilzkörperfremden Fasern im Stiel synaptisch verknüpft. Sehr wahrscheinlich konvergieren im unteren Stielteil Globulizellfasern auf postsynaptische extrinsische Fortsätze. Wahrscheinlich haben auch Globulizellfasern untereinander synaptischen Kontakt. 5. Synaptische SpezialStrukturen (elektronendichte Auflagerungen, Massierungen von synaptischen Vesikeln) finden sich größtenteils in den anliegenden Winkeln von zwei benachbarten Axonen. Oftmals kann eine Entscheidung über die Polarisierung der Synapsen nicht getroffen werden. 6. Die verschiedenen Fasertypen und ihre Kontakte über Synapsen werden im Hinblick auf die Funktion der Corpora pedunculata diskutiert, die nach verbreiteter Ansicht assoziative Hirnzentren verkörpern.
    Notes: Summary 1. The stalk of the mushroom-bodies (Corpora pedunculata) of the cricket Acheta domesticus L. is composed of nerve fibers from different types of globuli cells. These fibers are arranged into four groups. 2. Extrinsic nerve fibers run through the pedunculus neuropil in different directions. 3. Synapses occur primarily in stalk zone III and in basic stalk parts of zone IV. Intrinsic nerve fibers of globuli cells contain synaptic vesicles, which stain with ZIO-impregnation (Akert and Sandri, 1968), and dense core vesicles. 4. Intrinsic and extrinsic nerve fibers make synaptic contacts. There is some evidence, that globuli cell fibers interact by chemical synapses too. 5. Special synaptic structures such as electron dense projections and accumulations of vesicles are situated predominantly in the angles of two neighbouring axons. The question of synaptic polarization can not always be resolved. 6. The different fiber types and their synaptic contacts are discussed with respect to the function of the corpora pedunculata. The results support the general view, that mushroom bodies represent an important brain center for association.
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    Cell & tissue research 103 (1970), S. 48-60 
    ISSN: 1432-0878
    Keywords: Synaptosomes ; Glutaraldehyde/PTA ; Synapses ; Octopus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Octopus synaptosomes have been examined after glutaraldehyde fixation and phosphotungstic acid (PTA) staining of non-osmicated tissue. The results concentrate on the appearance of the contact region between the presynaptic component of synaptosomes and their postsynaptic processes. Membranes have a triple-layered appearance, consisting of an electronopaque internal coat, an electrontranslucent band and an electronopaque external coat. Good examples of this are found in synaptosomal, dendritic and axonal membranes. At specialized synaptic contact regions the external coats of the pre- and postsynaptic membranes coalesce to form a prominent synaptic plate, which has a width of 18 nm and is subdivided into zones of varying electronopacity. It is suggested that this plate is formed from the specialized external coat of the postsynaptic membrane and the unspecialized external coat of the presynaptic membrane. Presynaptic spicules extend from the internal coat of the presynaptic membrane. They are closely associated with elements of the presynaptic network. It is suggested that the synaptic plate is probably composed of mucopolysaccharides, while the relation of the plate to acetylcholinesterase is discussed. It is proposed that functional localization at the synapse is less precise in octopus than vertebrates.
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    Cell & tissue research 105 (1970), S. 276-302 
    ISSN: 1432-0878
    Keywords: Pineal organ ; Passer domesticus ; Synapses ; Nervous pathway ; Sympathetic innervation ; Photo-neuro-endocrine organ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Im Parenchym der Epiphysis cerebri von Passer domesticus kommen Nervenzellen vor. Ihre Neuriten ziehen im langgestreckten Epiphysenstiel zur Commissura habenularum. Im proximalen Endabschnitt des Epiphysenstiels wird ein Teil dieser Fasern myelinisiert. Zwischen die Nervenfasern schieben sich zahlreiche Pinealocytenausläufer; synaptische Bänder helfen die letzteren eindeutig zu identifizieren. Im Bereich der synaptischen Bänder liegen: 1. 300 Å Vesikel, 2. 300 Å Vesikel und 800–1200 Å Granula, 3. nur 800–1200 Å große granulierte Vesikel. Die Tatsache, daß in Pinealocytenausläufern nebeneinander synaptische Bänder und Granula vorkommen, und daß apikal in zilientragenden Zellen ebenfalls Granula nachweisbar sind, spricht dafür, daß bei Passer domesticus ein Pinealzelltyp sensorische und sekretorische Strukturmerkmale besitzen kann. Außerdem werden Kontaktsynapsen beobachtet; ihre praesynaptischen Fasern enthalten die gleichen Strukturelemente wie die Fasern mit synaptischen Bändern. Die Zahl der Mikrofibrillen und Mikrotubuli variiert in den Pinealocytenausläufern, in den postsynaptischen Dendriten und in den Neuriten so stark, daß es mitunter schwierig ist, diese Fortsatztypen einwandfrei zu unterscheiden und die Zahl der zum Gehirn ziehenden Neuriten exakt zu ermitteln. Efferente sympathische Nervenfasern dringen in die Bindegewebssepten der Epiphyse ein. Sie enthalten Granula mit einem Durchmesser von 300–500 Å und 800–1200 Å. Nach Injektion von Nialamid zeigen beide Granulatypen einen elektronendichten Kern. Mikrospektrographisch ist Serotonin und Noradrenalin in diesen Nervenfasern nachweisbar. Das Material dieser Studie enthält keinen fluoreszenzmikroskopischen oder elektronenmikroskopischen Hinweis darauf, daß die sympathischen Nervenfasern durch die Basalmembran in den Zellverband des Epiphysenparenchyms eintreten. Im elektronenmikroskopischen Bild haben manche Pinealocytenausläufer eine Ähnlichkeit mit autonomen Nervenfasern. Die funktionelle Bedeutung der Vogelepiphyse als photo-neuro-endokrines Organ wird diskutiert.
    Notes: Summary The pineal organ of Passer domesticus contains nerve cells within its parenchyma. Axons of the nerve cells run within the elongated stalk of the pineal organ to the habenular commissure. At the proximal end of the stalk, some axons become myelinated. In the stalk, the axons intermingle with pinealocyte processes containing synaptic ribbons. The synaptic ribbons are in contact with (1) vesicles with a diameter of 300 Å; (2) 300 Å diameter vesicles and 800–1,200 Å diameter dense-core granules; or (3) the dense-core granules only. Dense-core granules are also present in pinealocytes with 9+0 type cilia. These results suggest that sensory and secretory structures are present in the same pineal cell type. Furthermore, “conventional” synapses are present between receptor and nerve cells: The presynaptic fibers have the same structure as the fibers containing synaptic ribbons. The numbers of microfibrils and microtubules vary among postsynaptic fibers (dendrites), the pinealocyte processes, and the neurites. Thus it is difficult to obtain an exact count of the number of axons running to the brain. Efferent sympathetic nerve fibers enter the pineal organ associated with the connective tissue surrounding blood vessels. The fibers show granules of 300–500 Å diameter or 800–1,200 Å diameter. After nialamide injection, both types of granules contain a dense core. Microspectrographically serotonin and noradrenaline are demonstrated in the sympathetic nerve fibers. There is no evidence found in the material of this study to suggest that sympathetic nerve fibers perforate the basement membrane and enter the parenchymal cell complexes of the pineal organ. Pinealocyte processes and sympathetic nerve fibers often show a very similar ultrastructural pattern. The role of the avian pineal organ in photo-neuro-endocrine regulation is discussed.
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