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  • Articles  (108)
  • Development  (60)
  • pharmacokinetics  (48)
  • Springer  (108)
  • 2020-2020
  • 1970-1974  (108)
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  • Articles  (108)
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  • Springer  (108)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 12 (1973), S. 259-279 
    ISSN: 1432-0827
    Keywords: Osteocyte ; Calvarium ; Histology ; Development ; Calcium ; Phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des cartes tissulaires ainsi que les caractéristiques et propriétés cellularires ont été relevées au cours d'une étude de microscopie optique du développement de la calotte cranienne de souris, avant la naissance, jusqu'au 26ème jour. Les population d'ostéocytes de moitiés droite et gauche de ces calottes sont semblables, mais décroissent avec le temps dans un volume donné. De petites plages limitées de matrice osseuse se colorent pour le phosphate (ou carbonate) de façon plus nette que la matrice environnante, qui se colore légèrement après coupe. Les divers types ostéocytaires se distinguent par les réactions histochimiques du calcium et du phosphate, qui sont associés dans les cellules osseuses de façon complexe, variant dans le temps et la localisation. Ces deux constituants ne sont pas toujours présent dans les cellules des diverses régions, ou dans la même localisation dans un type cellulaire donné. En tenant compte des changements visible dans les divers types cellulaires avec le temps, dans des régions données, une hypothèse de “charge” et “décharge” cellulaire est émise.
    Abstract: Zusammenfassung Anläßlich einer mikroskopischen Studie über die Entwicklung des Mäuse-Calvariums von der Pränatalperiode bis zu 26 Tagen nach der Geburt wurden auch die Gewebetopographie sowie die Charakteristica und Eigenschaften der Zellen aufgezeichnet. Die Osteocyten-populationen in der linken und rechten Hälfte des Calvariums waren sich gleich, nahmen jedoch bei einem gegebenen Volumen mit der Zeit ab. Kleine isolierte Stellen von Knochen-matrix konnten leichter auf Ph sphat (oder Carbonat) angefärbt werden, als die umgebende Matrix, welche sich wohl am Schnitt, nicht aber am ganzen Stück färben ließ. Die verschiedenen Typen von Osteocyten wurden aufgrund histochemischer Calcium- und Phosphat-reaktionen bestimmt. Calcium und Phosphat waren innerhalb der Knochenzellen auf komplexe Art miteinander verbunden, die je nach Zeit und Lagerung unterschiedlich war. Zellen in abgetrennten Bereichen enthielten nicht immer Calcium und Phosphat und beide waren bei einer bestimmten Zellenart auch nicht immer am gleichen Ort abgelagert. Aufgrund der an ausgewählten Stellen beobachteten, zeitlich bedingten Veränderungen innerhalb der verschiedenen Zelltypen wird vorgeschlagen, daß es sich dabei um eine Sequenz von “Ladung” und “Entladung” der Zellen handelt.
    Notes: Abstract Tissue maps, and cell characteristics and properties were recorded in a study under the optical microscope of the development of the mouse calvarium from pre-natal to 26 days. Osteocyte populations in left and right halves of the calvarium were similar, but decreased with time for a given volume. Small isolated areas of bone matrix stained for phosphate (or carbonate) in a more readily available form from that in the surrounding matrix, which could be stained after sectioning but failed to stain in bulk. Osteocyte types were defined on the basis of histochemical methods for calcium and phosphate, which were associated inside bone cells in a complex manner, varying with time and position. The calcium and phosphate were not always present within the cell in discrete regions and were not always present in the same place in a given cell type. On the basis of a study of changes in cell types with time in selected sites a sequence of “loading” and “unloading” is proposed.
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  • 2
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    Calcified tissue international 16 (1974), S. 209-217 
    ISSN: 1432-0827
    Keywords: Mucopolysaccharides ; Collagen ; Calvarium ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Mucopolysaccharides (MPS) and collagen have been analyzed in different types of cartilage and some other tissues at various stages of prenatal and postnatal human development. The concentration of the chondroitin sulfate-type MPS increased from the 38th embryonal day, the 6-sulfate exceeding in amount the 4-sulfate. The increase in collagen concentration was accompanied by a decrease in the proportion of neutral salt-soluble collagen. There was no accumulation of chondroitin sulfates in the calvaria. A maximal concentration of MPS of a low molecular weight occurred in the skin and in the ear pinna after the 10th prenatal week. Postnatally, the MPS-concentration in the iliac crest and in the tibial articular cartilages decreased gradually, the highest values being reached in the newborn; the collagen-concentration showed an approximately reciprocal course.
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  • 3
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    Journal of molecular evolution 3 (1974), S. 109-113 
    ISSN: 1432-1432
    Keywords: “Custom Fitting” ; Development ; Evolution ; Antibody response ; Genetic Redundancy ; Perturbation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary When the complexity of a developmental system evolves to a certain point, appreciable variation must occur in the process. The problem the biologist faces is whether this point constitutes a limit to the evolution of complexity in developmental systems. If not, what mechanisms are employed to cope with the problem ? The problem—essentially one in “custom fitting” of parts, — and the possible solution(s) to it that have evolved are discussed. The antibody producing system appears to be one that “solves” the custom-fitting problem.
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  • 4
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    Calcified tissue international 7 (1971), S. 267-276 
    ISSN: 1432-0827
    Keywords: Tech ; Development ; Enamel ; Enzyme ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'activité en naphtylamidase est étudiéc au niveau des incisives et molaires de rat, à divers stades de développement. Du L-leucyl-4-methoxy-2-naphtylamide, du L-alanyl-4-methoxy-2-naphtylamide, du L-leucyl-2-naphthylamide et du DL-alanyl-2-naphtylamide sont utilisés comme substrats: du bleu rapide B et du grenat rapide GBC sont employés comme sels de diazonium. Le naphtylamidase n'est pas visible au niveau de dents, en voie de dévelopment, au cours de la formation matricielle de l'émail. A la fin de ce stade, le naphtylamidase est présent au niveau de l'extrémité distale des améloblastes, près de la surface de l'émail. L'activité enzymatique reste identique jusqu'au moment de la fusion de l'épithélium dentaire et de l'épithélium buccal, au moment de l'éruption de la dent dans la cavité buccale. On ne rencontre pas de naphtylamidase au niveau d'autres tissues dentaires; cependant une activité marquée est observée dans les ostéoclastes au niveau des surfaces de résorption de l'os alvéolaire, entourant les dents, en voie de développement et d'éruption, et dans certaines régions du tissu conjonctif.
    Abstract: Zusammenfassung Die Aktivität der Naphthylamidase wurde in den Backen- und Schneidezähnen von Ratten in verschiedenen Entwicklungsstufen studiert. Als Substrate wurden L-leucyl-4-methoxy-2-naphthylamid, L-alanyl-4-methoxy-2-naphthylamid, L-leucyl-2-naphthylamid und DL-alanyl-2-naphthylamid verwendet; als Diazoniumsalze dienten Echtblau B und Echt-Granat GBC. Naphthylamidase konnte während der Schmelzmatrixbildung im Zahn nicht nachgewiesen werden. Nach Abschluß dieser Phase erschien Naphthylamidase in den distalen Enden der Ameloblasten, nahe bei der Schmelzoberfläche. Die Enzymtätigkeit blieb am selben Ort lokalisiert, bis das Zahnepithel, im Augenblick wo der Zahn in die Mundhöhle durchstößt, in das Mundepithel überging. Naphthylamidase wurde in anderen Zahngeweben nicht gefunden, aber eine deutliche Aktivität konnte in gewissen Bezirken des Bindegewebes sowie in den Osteoklasten der resorbierenden Oberflächen vom alveolären Knochen festgestellt werden, welcher die sich bildenden und die hervorstoßenden Zähne umgibt.
    Notes: Abstract Naphthylamidase activity was studied in rat molar and incisor teeth at different stages of development. L-leucyl-4-methoxy-2-naphthylamide, L-alanyl-4-methoxy-2-naphthylamide, L-leucyl-2-naphthylamide and DL-alanyl-2-naphthylamide were used as substrates and Fast blue B and Fast Garnet GBC as diazonium salts. Naphthylamidase was not demonstrable in the teeth during enamel matrix formation. After the termination of this stage, naphthylamidase was present in the ameloblasts in their distal ends close to the enamel surface. The enzyme activity retained this localization until the dental epithelium fused with the oral epithelium at the time of tooth eruption into the oral cavity. Naphthylamidase was not found in other dental tissues, but marked activity was found in osteoclasts at the resorbing surfaces of alveolar bone surrounding the developing and erupting teeth and in certain areas of the connective tissue.
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  • 5
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    Calcified tissue international 9 (1972), S. 122-130 
    ISSN: 1432-0827
    Keywords: Tetracycline ; Development ; Calcification ; Statolith ; Nematocysts ; Aurelia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'effet de la tétracycline HCl sur la synthèse de statolithes de sulfate de calcium chezAurelia a été étudié. La tétracycline inhibe la synthèse de statolithes et nématocystes à un stade précoce de strobilation. La tétracycline, cependant, n'est pas incorporée dans les statolithes ou nématocystes en formation. Comme la tétracycline ne se combine pas avec le calcium des statolithes de sulfate de calcium dihydraté d'Aurelia, l'explication des effets d'inhibition sur la différenciation de statolithes et nématocystes ne semble pas liée avec un facteur en rapport avec l'incorporation. Des étudesin vitro de quatre systèmes inorganiques de calcium et de tétracycline montrent que le sulfate de calcium dihydraté (gypse) n'incorpore pas la tétracycline: il en est de même de son équivalent isostructural, le phosphate de calcium hydrogéné dihydraté (brushite). Le carbonate de calcium et le phosphate de calcium (apatite) incorpore la tétracycline. L'explication des différences de comportement du calcium peut être liée à la structure cristalline des composés respectifs, et, en particulier, au fait que l'ion Ca est prêt ou non à réagir avec la tétracycline.
    Abstract: Zusammenfassung Es wird über die Wirkung von Tetracyclinchlorhydrat auf die Synthese von Calciumsulfat-Statolithen beiAurelia berichtet. Wird das Tetracyclin in einem Frühstadium der Strobilation verabreicht, so hemmt es die Synthese der Statolithen und der Nematocysten. Das Tetracyclin wird jedoch nicht in die sich bildenden Statolithen oder Nematocysten eingebaut. Da sich das Tetracyclin nicht mit dem Calcium der Calciumsulfatdihydrat-Statolithen derAurelia verbindet, so kann dessen Hemmwirkung auf die Statolithen und die sich differenzierenden Nematocysten offenbar nicht mit einem einbaubedingten Faktor erklärt werden. Untersuchunge, die in vitro mit vier verschiedenen anorganischen Calciumsalzen und Tetracyclin ausgeführt wurden, zeigten, daß weder Calciumsulfatdihydrat (Gips), noch dessen isotrukturelles Aequivalent Calciumhydrogenphosphatdihydrat (Bruschit) Tetracyclin einbauen. Dagegen inkorporieren Calciumcarbonat und Calciumphosphat (Apatit) das Tetracyclin. Die Erklärung für dieses unterschiedliche Verhalten der Calciumsalze findet sich in der Kristallstruktur der betreffenden Verbindungen, d.h. es hängt davon ab, ob das Calciumion ür die Reaktion mit Tetracyclin leicht verfügbar ist.
    Notes: Abstract The effect of tetracycline HCl on synthesis of calcium sulphate statoliths inAurelia is reported. Tetracycline inhibits synthesis of statoliths and nematocysts when administered at an early stage of strobilation. The tetracycline, however, is not incorporated into the developing statoliths or nematocysts. As the tetracycline does not combine with the calcium of the calcium sulfate dihydrate statoliths ofAurelia, an explanation for its inhibitory effects on statoliths and nematocyst differentiation apparently does not rest with an incorporation-related factor. In vitro studies of four inorganic calcium systems and tetracycline revealed that calcium sulfate dihydrate (gypsum) did not incorporate tetracycline nor did its isostructural equivalent, calcium hydrogen phosphate dihydrate (brushite). Calcium carbonate and calcium phosphate (apatite) did incorporate tetracycline. The explanation for these different behaviors of calcium can be found in the crystal structure of the respective compounds, namely, whether or not the Ca ion is readily available to react with tetracycline.
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  • 6
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    Calcified tissue international 9 (1972), S. 173-178 
    ISSN: 1432-0827
    Keywords: Phosphatase ; Development ; Bone ; Growth ; Rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une étude longitudinale, par séries, est effectuée pour déterminer les activités en phosphatases acide et alcaline dans les os longs et la mandibule. Le pH optimum des deux enzymes se situe respectivement à 10.2 et 5.4 pour les phosphatases alcaline et acide. Des portées synchronisées de rats sont sacrifiées, à raison d'une portée par jour, en commençant au premier jour jusqu'au 25ème jour post-partum. Les spécimens sont analysés en ce qui concerne leur concentration en protéine et leur activité en phosphatases. Une activité de types élevée et faible est observée au niveau du tissu osseux, ainsi qu'un type d'activité faible en phosphatase alcaline, au cours des pics d'activité en phosphatase acide, et vice-versa. Les pics observés suggèrent une concordance entre l'activité en phosphatase et les autres changements biochimiques de la croissance osseuse, au niveau de la matrice organique et la formation minérale. Une étude séparée, tenant compte de la possibilité d'une activité enzymatique rythmique, suggère l'existence d'un rythme diurne court chez les animaux jeunes.
    Abstract: Zusammenfassung Eine serienmäßige Longitudinaluntersuchung wurde unternommen, um die Aktivitäten der alkalischen und sauren Phosphatase in den Röhrenknochen und den Mandibulae von Ratten zu bestimmen. Das pH-Optimum der beiden Enzyme wurde für die alkalische Phosphatase bei 10,2 und für die saure Phosphatase bei 5,4 ermittelt. Synchronisierte und randomisierte Würfe wurden getötet, 1 Wurf pro Tag vom 1.–25. Tag post partum. Die Proben wurden auf ihren Proteingehalt und ihre Phosphatasenaktivität untersucht. Ein Muster niedriger und hoher Aktivität konnte in beiden Knochengeweben beobachtet werden, sowie ein Muster von niedriger Aktivität der alkalischen Phosphatase bei Spitzenwerten der sauren Phosphatase und umgekehrt. Die beobachteten Spitzenwerte lassen einen Zusammenhang vermuten zwischen der Phosphatasenaktivität und den anderen biochemischen Veränderungen, die im wachsenden Knochen auftreten, d. h. Bildung der organischen Matrix und des Minerals. Eine getrennte Untersuchung, welche sich mit der Möglichkeit rhythmischer Merkmale der Enzymaktivität befaßte, läßt vermuten, daß in den ersten Tagen ein schwacher Tagersrhythmus bestehen könnte.
    Notes: Abstract A serial longitudinal study was undertaken to determine the activities of the alkaline and acid phosphatases in the long bones and mandibles. The optimum pH of the two enzymes was recorded at 10.2 and 5.4 for alkaline and acid phosphatase, respectively. Synchronized and randomized litters of rats were killed, 1 litter daily, starting at day 1 to day 25 post partum. Samples were analyzed for protein concentration and activity of the phosphatases. A pattern of low and high activity was observed in both bony tissues, as well as a pattern of low alkaline phosphatase activity during acid phosphatase activity peaks, and vice versa. The observed peaks suggest a correspondence between phosphatase activity and the other biochemical changes occurring in the growing bone, i.e., organic matrix and mineral formation. A separate study, considering the possibility of rhythmic features of the enzyme activity suggests that there may be a small diurnal rhythm at an early age.
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  • 7
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 8
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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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  • 9
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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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  • 10
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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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  • 11
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    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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  • 12
    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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  • 13
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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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  • 14
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 15
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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 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 7 (1974), S. 375-380 
    ISSN: 1432-1041
    Keywords: Tranexamic acid ; pharmacokinetics ; man ; antifibrinolytic agents ; renal clearance ; two-compartment model
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    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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  • 18
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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
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    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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  • 19
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    European journal of clinical pharmacology 7 (1974), S. 25-29 
    ISSN: 1432-1041
    Keywords: Pindolol ; uraemia ; pharmacokinetics ; β-blockade
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    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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  • 20
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    European journal of clinical pharmacology 7 (1974), S. 59-60 
    ISSN: 1432-1041
    Keywords: Pizotifen ; isonicotinylhydrazine ; orexigen ; tuberculosis ; pharmacokinetics
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    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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  • 21
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    European journal of clinical pharmacology 7 (1974), S. 31-37 
    ISSN: 1432-1041
    Keywords: Diphenylhydantoin ; uraemia ; protein binding ; pharmacokinetics
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    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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  • 22
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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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  • 23
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    Archives of microbiology 96 (1974), S. 353-364 
    ISSN: 1432-072X
    Keywords: Coprinus ; Agaricaceae ; Mushroom ; Development ; Growth Regulator ; Stipe Growth
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    Topics: Biology
    Notes: Abstract Some of the morphological and physiological parameters of stipe growth or elongation inCoprinus radiatus were investigated. During the development of the fruit body the number of cells in a row in the growing portion of the stipe doubled during the development of the button, and again during the phase of rapid stipe elongation. Also during the stage of rapid elongation the cells in the upper 2/3 of the stipe increased 6–8 fold in length. The existence of a growth regulator synthesized in the cap and exerting control over the stipe was demonstrated through decapitation experiments. The cap appears to be required for normal stipe development until the stipe reaches about 1/4 of its final length. Through decapitation and cap-stipe exchanges it was found that the cap produced growth regulator up to the time of autodigestion; however, the stipe responded to the regulator only during a brief period at the onset of elongation.
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    Archives of microbiology 99 (1974), S. 331-344 
    ISSN: 1432-072X
    Keywords: Myxomycetes ; Ultrastructure ; Development ; Systematics ; Food Vacuoles ; Stalk Development
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    Topics: Biology
    Notes: Abstract Observations of sporophore development in fresh and glutaraldehydeosmium sequentially-fixed material ofProtophysarum phloiogenum show the following sequence. Small plasmodia cease streaming and round up. Food vacuoles collect in the lower center of the cytoplasmic mass. As the cytoplasm rises the food vacuolar contents are excluded from the plasmalemma and become the stalk core. A continuous, fibrous peridium and stalk tube enclose cytoplasm and stalk core respectively. Capillitial formation just precedes spore cleavage. Sporophore development is marked by autophagic activity and calcium deposition. Stalks of dried herbarium specimens of seven additional species have been examined. A mature stalk morphology very similar toProtophysarum with recognizable remnants of microorganismal food material is seen in all of them. It is thought that this marker is indicative of non-stemonitaceous stalk development.
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  • 25
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    Archives of microbiology 99 (1974), S. 155-166 
    ISSN: 1432-072X
    Keywords: cAMP ; Acanthamoeba ; Development
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    Topics: Biology
    Description / Table of Contents: Zusammenfassung Durch drei verschiedene Methoden wurde in Kulturen vonAcanthamoeba castellanii die stationäre Wachstumsphase, in deren Verlauf sich Trophozoiten zu Cysten entwickeln, induziert: Durch Nahrungsmangel, indem Amöben der logarithmischen Wachstumsphase in ein nährstofffreies Medium überführt wurden, durch Sauerstoffmangel, indem Kulturen zu großer Zelldichte heranwuchsen, und durch Hemmung der mitochondrialen DNS-Synthese, indem Kulturen der logarithmischen Phase mit Äthidiumbromid versetzt wurden. Unabhängig von den Encystierungsbedingungen nimmt die intracelluläre Konzentration von Adenosin-3′,5′-monophosphat (cAMP) bei Verminderung der Zellteilungsrate bis zu Beginn der stationären Wachstumsphase um das 2–3 fache zu. Die Ergebnisse deuten an, daß der Anstieg von intracellulärem cAMP auf eine Erhöhung der Adenylat-Cyclase- und nicht auf eine Verminderung der Phosphodiesterase-Aktivität zurückzuführen ist. Extracelluläres cAMP konnte weder in Kulturen der logarithmischen noch in Kulturen der stationären Phase nachgewiesen werden. Dies ist vermutlich auf die extracellulär vorhandene cAMP-Phosphodiesterase zurückzuführen. Die Tatsache, daß auch durch Theophyllin die stationäre Wachstumsphase und Encystierung induziert werden kann, läßt auf eine Beteiligung von cAMP an den Entwicklungsprozessen, speziell an dem Abbau von Glykogen, schließen.
    Notes: Abstract In cultures ofacanthamoeba castellanii the stationary growth phase in which trophozoites develop to cysts, was induced in three ways: by transferring cells from a logarithmic growing culture into a nutrient-free medium, by growth in nutrient medium to high cell density and by inhibition of the mitochondrial DNA synthesis with ethidium bromide. In all cases, the intracellular concentration of adenosine-3′,5′-monophosphate (cAMP) rises by a factor of two to three from the end of the logarithmic phase to the beginning of the stationary phase. The results show that this rise may be more a consequence of an increased adenylate cyclase activity than of a diminished cAMP phosphodiesterase activity. No extracellular cAMP could be measured in cultures of the logarithmic and stationary growth phase, perhaps because of the extracellular cAMP phosphodiesterase. Because theophylline also induces the stationary phase and encystation, cAMP seems to be of importance for the development ofAcanthamoeba castellanii, especially for the degradation of glycogen.
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  • 26
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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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  • 27
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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 7 (1974), S. 51-58 
    ISSN: 1432-1041
    Keywords: Rifampicin ; plasma level ; pleural fluid concentration ; microbiological assay ; pharmacokinetics
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    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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  • 29
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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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  • 33
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    European journal of clinical pharmacology 7 (1974), S. 17-24 
    ISSN: 1432-1041
    Keywords: Pindolol ; beta-blockade ; pharmacokinetics ; man
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    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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    European journal of clinical pharmacology 7 (1974), S. 119-124 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; phenytoin ; diphenylhydantoin ; bioavailability ; generic inequivalence ; pharmacokinetics
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    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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    European journal of clinical pharmacology 7 (1974), S. 217-225 
    ISSN: 1432-1041
    Keywords: Rifampicin ; p-aminosalicylic acid ; drug interaction ; isoniazid ; pharmacokinetics ; antituberculous therapy
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    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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    European journal of clinical pharmacology 7 (1974), S. 249-252 
    ISSN: 1432-1041
    Keywords: Practolol ; renal failure ; uraemia ; beta-blockade ; pharmacokinetics ; man
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    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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    European journal of clinical pharmacology 3 (1970), S. 3-11 
    ISSN: 1432-1041
    Keywords: Amphetamine ; drug dependence ; pharmacokinetics ; amphetamine psychosis
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    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 4 (1971), S. 32-37 
    ISSN: 1432-1041
    Keywords: Glibenclamide ; pharmacokinetics ; metabolism ; potentiation of hypoglycemic action ; phenylbutazone
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    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 (1970), S. 36-42 
    ISSN: 1432-1041
    Keywords: Sulphonamides ; sylfametopyrazine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    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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  • 40
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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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  • 41
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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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  • 42
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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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  • 43
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    Archives of microbiology 101 (1974), S. 391-399 
    ISSN: 1432-072X
    Keywords: Adenosinephosphate System ; Energy Charge ; Acanthamoeba ; Development
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    Topics: Biology
    Description / Table of Contents: Zusammenfassung Die Konzentration von Adenosintri-, Adenosindi- und Adenosinmonophosphat wurde in Acanthamoeba castellanii währed der logarithmischen Wachstumsphase und der stationären Wachstumsphase, in deren Verlauf sich Trophozoiten zu Cysten entwickeln, bestimmt. Der Entwicklungsprozess wurde durch drei verschiedene Methoden hervorgerufen: Durch Wachstum im Nährmedium zu großer Zelldichte, durch Überführen von Amöben der logarithmischen Wachstumsphase in ein nährstoffreies Salzmedium und durch Versetzen logarithmisch wachsender Amöben mit Äthidiumbromid. In allen Fällen wird der Adenosinphosphat-Gehalt in den Zellen im Laufe der Entwicklung um etwa 85% reduziert, wozu besonders die Abnahme des ATP-Gehaltes beiträgt. Die Adenosinphosphat-“energy charge” beträgt in logarithmisch wachsenden Amöben 0,83. Im Laufe der Entwicklung wird sie je nach Encystierungsbedingungen auf unterschiedlichen Werten stabilisiert (zwischen 0,58 und 0,81). Die Möglichkeit eines Zusammenhanges von Konzentrationsveränderungen der Adenosinphosphate und entwicklungsspezifischen Prozessen wird diskutiert.
    Notes: Abstract The concentration of adenosine tri-, adenosine di-, and adenosine monophosphate in cells of Acanthamoeba castellanii was measured during the logarithmic growth phase and the stationary growth phase in which trophozoites were transformed into cysts. This developmental process was induced in three ways: by growth in nutrient medium to high cell density, by transferring cells in the logarithmic phase into a nutrient-free medium, and by mixing logarithmically growing cells with ethidium bromide. In all cases, encystment is accompanied with a reduction of total adenosine phosphate content to about 85%, mainly because of a depletion of cellular ATP. The value of the adenosine phosphate energy charge in logarithmically growing amoebae is 0.83. During development the energy charge becomes stabilized at different values (between 0.58 and 0.81), characteristic to the mode of encystation. A possible functional relationship between changes of the adenosine phosphate concentration and developmental processes of the amoeba is discussed.
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  • 44
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    Cell & tissue research 108 (1970), S. 380-396 
    ISSN: 1432-0878
    Keywords: Epicuticle ; Insects ; Tenebrio molitor ; Development ; Structure
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    Topics: Biology , Medicine
    Description / Table of Contents: Résumé L'épicuticule de l'adulte de Tenebrio molitor est composée de deux couches distinctes dénommées épicuticule externe et épicuticule interne. L'épicuticule externe est la première couche cuticulaire sécrétée sous forme de petites plaques s'agrandissant par leurs bords pour recouvrir toute la surface cellulaire. Au moment de sa sécrétion, cette couche est formée de quatre lames denses A, B, C1 et C2. La lame B, très fine, disparaît par la suite et les lames C1 et C2 deviennent très nettes. L'épicuticule externe de l'adulte est donc formée de trois lames denses séparées par deux lames claires. L'épicuticule interne est formée de lames superposées denses et claires de structure complexe, qui sont masquées pendant la sécrétion des premières couches de cuticule lamellée (procuticule). Cette structure correspond à un arrangement moléculaire hautement organisé. La forme de la surface cuticulaire des sternites est déterminée par la forme de la surface cellulaire avant le dépôt de l'épicuticule.
    Notes: Summary The epicuticle of adult Tenebrio consists of two distinct layers named outer and inner epicuticle. The outer epicuticle is the first cuticular layer to be deposited in form of small patches on top of the microvilli. These initial patches are composed of four dense laminae (A, B, C1 and C2) separated by three light spaces. The outer epicuticle grows by densification of diffuse material at the edges of the patches until the entire area is covered. The thickness of outer epicuticle remains constant (175 Å) during the development of the pharate adult, lamina B however rapidly disappears. Thus, the adult outer epicuticle is fivelayered (three dense laminae: A, C1 and C2). After being deposited, the inner epicuticle shows a complex laminar structure interpreted to represent a highly organized molecular system. The laminae are masked during the formation of the first procuticle lamellae. During the deposition of the epicuticle, lamina A is covered by a component of the moulting fluid, forming an irregular dense layer which disappears after the resorption of this fluid. Perhaps this layer protects the new epicuticle from lytic enzymes of the moulting fluid. In adult animals, there is an additional superficial layer, the signification of which is not clear. The possibility of remains of cement or wax is discussed. The development of the surface patterns of the sternal and pleural cuticle is determined before the epicuticle formation by the shape of the epidermal surface. The rate of outer epicuticle deposition appears to depend on the size of the microvilli: epicuticle deposition seems to proceed faster over high microvilli.
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  • 45
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    Cell & tissue research 109 (1970), S. 1-14 
    ISSN: 1432-0878
    Keywords: Seminal vesicle ; Prostate ; Fetal rat ; Ultrastructure ; Development
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    Topics: Biology , Medicine
    Notes: Summary The development of the seminal vesicle from the Wolffian duct and of the prostate from the urogenital sinus has been studied in rat fetuses from day 14 of gestation to birth with the use of the electron microscope. Prior to the onset of androgen secretion, the cells of the urogenital sinus and the caudal part of the Wolffian duct have a simple undifferentiated appearance. After the onset of androgen secretion by the fetal testes at day 15, “intracytoplasmic confronting cisternae” of the granular reticulum appear in both urogenital sinus and Wolffian duct. Portions of the granular endoplasmic reticulum of the urogenital sinus become distended with a finely granular, moderately dense material. In the urogenital sinus, many hemidesmosomes are formed at the basal surface of the epithelium. Specializations of the extracellular materials are present opposite the hemidesmosomes. The formation of the seminal vesicles and the prostate begins at day 18–19 of gestation. The cells of the seminal vesicle are taller than the Wolffian duct cells from which they arise, the granular endoplasmic reticulum increases moderately in amount, and a patent lumen is formed. The cells of the fetal prostate do not differ greatly from those of the urogenital sinus from which they arise except that the prostatic cells initially lack hemidesmosomes. The fine structural changes are discussed in relation to the onset of fetal androgen secretion, the formation of the organs, and the functions of the cells in adult life.
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    Cell & tissue research 111 (1970), S. 346-363 
    ISSN: 1432-0878
    Keywords: Kidney ; Glomerulus ; Development ; Scanning electron microscopy
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    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Differenzierung der Podocyten wurde an Nieren 10 Tage alter Ratten raster-elektronenmikroskopisch untersucht und mit durchstrahlungs-elektronenmikroskopischen Befunden verglichen. Die Podocytenfortsätze können danach auf dreierlei Wegen gebildet werden: 1. Spalten innerhalb des Cytoplasmas lassen bandartige Cytoplasmabrücken entstehen. Diese gliedern sich weiter auf, bis zahlreiche miteinander verzahnte Fortsätze derselben Zelle entstanden sind. 2. Vom Zellrand her werden dicke Fortsätze weit vorgeschoben, die kleinere Fortsätze bilden. Durch sie können Verzahnungen mit entfernten Deckzellen entstehen. Die kleinen Fortsätze können sich jedoch auch mit anderen Fortsätzen der eigenen Zelle verzahnen. 3. Fingerförmige Fortsätze benachbarter Zellen verzahnen sich während ihrer Entstehung miteinander. Trotz zahlreicher desmosomenartiger Haftstellen zwischen benachbarten Podocyten entwickeln sich ihre Fortsätze und deren Verzahnungen anscheinend weitgehend autonom und nur selten nach den vermuteten Regeln epithelialer Nachbarschaft (Typ 3). Die Befunde sprechen vielmehr dafür, daß durchflutete und wachsende Glomerulumkapillaren die Podocytendifferenzierung induzieren und die Orientierung der Fortsätze beeinflussen.
    Notes: Summary The differentiation of the podocytes was studied by scanning electron microscopy on kidneys of 10 days old rats. The results were compared with transmission electron microscopic pictures from the same kidneys. There are three ways of forming processes by the podocytes: 1. Slits within the cytoplasm give rise to cytoplasmic bridges which further divide themselves and finally build up a meshwork of processes within a cell. 2. Thick and sometimes very long processes originate from the cell border. Their smaller branches may interdigitate with those of distant podocytes or with other processes out of the same cell. 3. Finger-like processes of neighbouring cells interdigitate as soon as they develop. In spite of numerous desmosomal structures between neighbouring podocytes the cell processes and their interdigitations develop mostly independently from each other and only seldom after the expected rules of epithelial vicinity (type 3). These findings are interpreted as indication that flooded and growing capillaries induce the differentiation of podocytes and that they influence the orientation of their processes.
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  • 47
    ISSN: 1432-0878
    Keywords: Chemoreceptor ; Locusta ; Fine structure ; Development ; Moulting
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    Topics: Biology , Medicine
    Notes: Summary The basic structure of the terminal sensilla of Locusta migratoria resembles that of Schistocerca gregaria. There are commonly six or ten neurons whose dendrites extend almost to the opening of the peg. Proximally the dendrites are clothed by a neurilemma cell which also encloses a basal cavity through which their ciliary region passes. The tormogen cell encloses the receptor-lymph cavity and actively secretes material into it. The receptor-lymph cavity and the basal cavity are quite separate. The development of new pegs at a moult is described. After apolysis the scolopale extends across the subcuticular space and protects the dendrites, which remain in a functional condition until shortly before ecdysis. As the trichogen cell grows out to form a new peg the tip is surrounded by a mass of electron-dense material, probably derived from the receptorlymph cavity. The function of this material is unknown. Regeneration of the dendrites is considered. The possible mechanism by which the tip of the peg opens and closes is considered and the general structure of the organule is discussed in relation to functioning.
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  • 48
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    Keywords: Nervous system ; Stick insect ; Blood-brain barrier ; Development ; Electron microscopy
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    Notes: Summary The fat body sheath which surrounds the ventral nerve cord of the adult stick insect, Carausius morosus, is absent in the hatchling. Since the haemolymph sodium ion compositions of the two stages are similar, it is suggested that the fat body sheath is not a site of a blood-brain barrier dealing with extra-axonal regulation of sodium. Similarities of ultrastructure in connectives of adults and hatchlings are demonstrated, and tight junctions are shown to occur in perineural cells of both stages. The possible significance of this to the blood-brain barrier of this insect is discussed.
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    Cell & tissue research 106 (1970), S. 348-370 
    ISSN: 1432-0878
    Keywords: Ovary ; Insect ; Chironomus ; Development ; Ultrastructure
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    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Im Ovar von Chironomus sind in Phase 1 des 4. Larvenstadiums polygonal abgeflachte „Innenzellen“ von kleineren „Außenzellen“ umgeben, die Bakteroide und Phagosomen enthalten; zwischen den Innenzellen liegen unregelmäßige Zelltrümmer („keimbahnbegleitende Substanzen“). Zu Beginn der Ovariolenbildung werden in Phase 3 durch Spalträume zwei Schichten der Außenzellen voneinander getrennt, von denen die innere (Follikel- und Eikanalepithel) regelmäßige Buchten bildet. In diese Buchten wandern von innen Zellpaare ein, die an „synaptischen Komplexen“ bzw. multiplen Chromatinstrukturen als Ei- und Nährzellen kenntlich sind. Zwischen beiden Zellen sind „Fusome“ häufig, die später in eigentümlicher Weise geschlossen werden. Zwischen den Eikanalzellen entsteht in Phase 5 durch Spaltbildung der Eikanal; in Phase 7 sind die Eikanalzellen auffallend glykogenreich. Kurz vor der Vitellogenese treten im Bereich der Oocyte Membransysteme und „annulated lamellae“ auf; akzessorische Kerne werden als Ausstülpungen des Oocytenkernes gebildet und später abgeschnürt. In Phase 9 sind an der Peripherie der Eizelle Mikrovillisäume und Pinocytosebläschen sichtbar. Die distalen Zellen der Ovariole haben Eioder Nährzellcharakter, sind aber bei Ch. melanotus nicht von Follikelzellen umgeben und werden beim weiteren Ovariolenwachstum reduziert. Trotz extrem geringer Nährzellzahl der Follikel scheint das Chironomus-Ovar funktionell nicht von anderen polytroph meroistischen Insektenovarien unterschieden.
    Notes: Summary In the ovary of Chironomus during phase 1 of the fourth larval instar, polygonally flattened “inner cells” are surrounded by smaller “outer cells” which contain bacteroids and phagosomes. Irregular cell remnants (“germ line accompanying substances”) lie among the inner cells. At the beginning of ovariole formation in phase 3, two layers of outer cells are separated by the formation of fissures. The inner layer of these cells (follicle- and egg-passage epithelium) forms regular invaginations. Cell pairs, identified as oocytes and nurse cells by “synaptic complexes” or multiple chromatin structures, wander from inside into the invaginations. Frequently between the two cells are fusomes, which later close in a characteristic manner. During phase 5, an egg passage is formed as a fissure among the egg-passage cells. During phase 7, the egg passage cells are conspicuously full of glycogen. Shortly before vitellogenesis membrane systems and annulated lamellae appear in the region of the oocyte. Accessory nuclei are formed by a “tieing-off” of projections of the the oocyte nucleus. During phase 9, microvilli and pinocytotic vesicles can be seen at the periphery of the oocyte. The distal cells of the ovariole are of oocyte or nurse cell nature, but in Ch. melanotus they are not surrounded by follicle cells and are reduced during further ovariole growth. In spite of the extremely small number of nurse cells in the follicle, the Chironomus ovary apparently does not differ functionally from other polytrophic meroistic insect ovaries.
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    Cell & tissue research 147 (1973), S. 75-85 
    ISSN: 1432-0878
    Keywords: Skeletal muscle ; Denervation ; Development ; Fiber types, myofibrils ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Ultrastructural diversification of muscle fibers, with regard particularly to myofibrillar changes, has been investigated in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus muscles of the rat during fetal and postnatal development in the presence and in the absence of motor innervation. The band pattern and the shape of the myofibrils were uniform in fetal and neonatal muscle fibers and underwent differential changes during the first weeks after birth, concomitantly with fiber type specialization. The most evident variations in myofibrillar structure arising in this period concern the thickness of the Z band and the arrangement of the myofibrils. Myofibril formation was at first not impaired by denervation of rat muscles performed in utero and, although focal disintegration of myofibrils and detachment and loss of orientation of filaments became apparent by one week, atrophic muscle fibers with well-organized myofibrils could be seen as late as 2 months after birth. However, denervated muscle fibers of EDL and soleus did not display any significant and consistent difference in myofibrillar band pattern and shape. No variation in mitochondrial content and sarcoplasmic reticulum development was likewise seen in muscle fibers of EDL and soleus after fetal denervation. The findings emphasize the importance of neuromuscular interactions in muscle differentiation.
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    Cell & tissue research 147 (1974), S. 325-334 
    ISSN: 1432-0878
    Keywords: Chordotonal (Tracheal) organ ; Teleogryllus commodus (Orthoptera) ; Hearing ; Development ; Structure
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    Topics: Biology , Medicine
    Notes: Summary The tracheal organ of the mesothoracic tibia of Teleogryllus is located in a corresponding position to the tympanal organ of the prothoracic tibia. The mesothoracic organ contains an average of only 12 scolopidia, the location of which corresponds to that of the proximal group A and proximal main group in the prothoracid tympanal organ. There are no scolopidia corresponding to the distal group of the tympanal organ. The variability in number of scolopidia is much greater in the mesothoracic organ than in the prothoracic organ. The adult tracheal system of the mesothoracic leg resembles the early nymphal tracheal system in both pro- and meso-thoracic legs. The development of the tracheal organ is usually complete by the sixth instar. The mesothoracic tracheal organ of the adult is broadly equivalent to the prothoracic tympanal organ of a fifth instar animal.
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  • 52
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    Cell & tissue research 148 (1974), S. 535-550 
    ISSN: 1432-0878
    Keywords: Synaptosomes ; Rat brain stem ; Synaptogenesis ; Development ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The ultrastructure and protein content of the five subfractions of the crude mitochondrial fraction from the brain stem of the 1-day old and adult rat was examined. The morphological composition of the subfractions after fixation in glutaraldehyde and osmiumtetroxide in the adult rat brain stem resembled that previously reported for the whole brain; synaptosomes sedimented in a sucrose gradient in subfractions C and D. In the 1-day old rat, mature synaptosomes were found in subfractions A, B, C and D; E contained mainly free mitochondria. 80–95% of the processes in the adult and 10–30% in the 1-day old rat contained synaptic vesicles which were of four types: (1) small agranular vesicles (2) large dense core vesicles (3) large agranular vesicles (4) coated vesicles. Pre- and postsynaptic membrane thickenings were demonstrated in many nerve-ending particles. In the subfractions of the 1-day old rat the protein content was one half and the distribution resembled that in the adult. Evidently nerve endings develop faster in the brain stem than in cortical areas; a serotoninor adrenergic origin of the early synaptosomes is suggested.
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    Cell & tissue research 144 (1973), S. 435-452 
    ISSN: 1432-0878
    Keywords: Muscle spindles ; Intrafusal fibre types ; Development ; Deefferentation ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary Muscle spindles of limb muscles were deefferented in neonatal rats by sectioning ventral roots or by removal of the lumbosacral spinal cord. Ten to 56 days after the operation, muscle spindles were examined in the medial gastrocnemius, extensor digitorum longus and soleus muscles. The differentiation of muscle spindles was not affected by deefferentation. The number of spindles in the investigated muscles was not reduced. Intrafusal fibres increased in number from two at birth to four per spindle on the average, as in normal muscles. The characteristic ultrastructural distinctions of nuclear bag and nuclear chain fibres developed as under normal conditions. However, intrafusal fibres atrophied slowly after fusimotor denervation, their polar zones becoming reduced in diameter by about 25% in comparison with control fibre diameters. Spindle capsules, on the other hand, increased in size and attained diameters comparable with normal spindles, appearing even somewhat distended. As intrafusal fibres degenerate after complete denervation at birth (Zelená, 1957), but differentiate in the absence of fusimotor innervation, it can be concluded that sensory nerve terminals induce and support their development. It is assumed that the morphogenetic influence of sensory terminals is mediated by release and uptake of a trophic substance at the synaptic junction. The occurrence of light and dense core vesicles in the sensory terminals and of coated invaginations and vesicles at both the axonal and plasma membrane speak in favour of such a possibility.
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  • 54
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    Cell & tissue research 150 (1974), S. 425-442 
    ISSN: 1432-0878
    Keywords: Glandula submandibularis (Mouse) ; Acinar ultrastructure ; Cell types ; Development ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of the submandibular gland of the mouse was studied by means of electron microscopy, from the 14th day of gestation up to birth. In the first two days the acini are solid and their cells contain polyribosomes and a few lamellae of endoplasmic reticulum. Beginning with the 16th day secretory granules appear and rapidly fill an increasing number of cells. The different electron density of the granules makes it possible to distinguish 1. two types of granules, dense and pale, and sometimes intermediate ones, 2. “polymorphic” granules. The latter consists of electron dense and electron pale parts combined in different configurations. The possible significance of the various types of granules is discussed.
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    Cell & tissue research 151 (1974), S. 433-456 
    ISSN: 1432-0878
    Keywords: Juxtaglomerular apparatus (Rat) ; Development ; Renin ; Pools ; Electron microscopy
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    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die perinatale Entwicklung des juxtaglomerulären Apparates, insbesondere das Verhalten der epitheloiden Zellen wurde an 18 trächtigen Ratten and 65 Embryonen bzw. Jungtieren elektronenmikroskopisch untersucht. Parallel dazu wurde die Reninkonzentration bzw. der Reningehalt bestimmt. Spezifische Sekretgranula finden sich erstmals am 18. Tag der Fetalzeit, und zwar in den epitheloiden Zellen des juxtaglomerulären Apparates juxtamedullärer Nephrone. Die Granula machen einen Struktur- und wahrscheinlich auch Funktionswandel durch, der eine Einteilung in drei verschiedene Granulatypen nahelegt. Diesen drei Typen spezifischer (reninhaltiger) Sekretgranula werden die Lysosomen als unspezifische Einschlüsse der epitheloiden Zellen gegenübergestellt. Im einzelnen kommt es während der perinatalen Phase in den fetalen Epitheloidzellen zuerst, d.h. pränatal, zu einer Hypertrophie des rauhwandigen endoplasmatischen Retikulums und des Golgi-Apparates. Hierin sehen die Autoren einen Hinweis auf eine erhöhte Proteinsynthese mit entsprechender Zunahme der Transport- und Konzentrationsvorgänge. Nach der Geburt findet sich dann auch eine deutliche Zunahme der Sekretgranula vom Typ III, die als reife Reningranula (mature granules) angesehen werden. Die bisher noch nicht beschriebenen kleinen Sekretgranula vom Typ I dagegen kommen in weniger entwickelten Epitheloidzellen häufiger vor. Bestimmungen der Reninverteilung zwischen Zytoplasma und den durch Differential-zentrifugation gewonnenen Granula-Fraktionen ergeben auffallende Parallelen zu den morphologischen Befunden. Diese sprechen im allgemeinen dafür, daß “freies Renin” im Ergasto-plasma und “gebundenes Renin” in den Sekretgranula vorliegt. Mit zunehmendem Alter scheint es außerdem — parallel zur relativen Abnahme des Ergastoplasmas und Zunahme der reifen Reningranula — zu einer Verminderung des extragranulären zugunsten des granulär gebundenen Renins zu kommen.
    Notes: Summary The perinatal development of the Juxtaglomerular apparatus (JGA), with particular reference to the epithelioid cells, was studied. Electron microscopic studies were carried out on 18 gravid rats and 65 embryos with corresponding determinations of renin concentration and the renin contents by bio-assay. Specific secretory granules of the epithelioid cells of the JGA of juxtamedullary nephrons are first observed on the 18th day of gestation. The classification into three types of secretory granules suggests that they undergo a structural and probably also a functional transformation. All three types of secretory granule may be regarded as specific, renin-containing, cytoplasmic organelles. During the last days of gestation, the rough-surfaced endoplasmic reticulum and the Golgi apparatus become hypertrophied in epithelioid cells, indicating an increased protein synthesis as well as transport and concentration processes. After birth, there is a definite increase in the number of Type III secretory granules-which may be regarded as mature granules. The small Type I secretory granulesnot previously described-are found more frequently in the immature epithelioid cells. Determinations of the renin distribution in the plasma and in fractions of cytoplasmic constituents (total homogenate, secretory granules) prepared by differential centrifugation showed striking congruence with the morphological findings. It is generally assumed that “soluble renin” occurs in the endoplasmic reticulum and “bound renin” in secretory granules. A shift from extragranular to granular (bound) renin, occurs with increasing age, having its morphological equivalent in the relative decrease of the endoplasmic reticulum and increase in mature secretory granules.
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    Cell & tissue research 153 (1974), S. 115-136 
    ISSN: 1432-0878
    Keywords: Muscle spindles ; Intrafusal fibre types ; Development ; De-efferentation ; Utrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Hind limb muscles were de-efferented in 19 new-born rats by removal of the lumbosacral spinal cord, with preservation of spinal ganglia and their peripheral branches. The juxtaequatorial and polar zones of muscle spindles were studied in different leg muscles 3 to 9 weeks after the operation in order to establish whether intrafusal fibre types would become differentiated after permanent motor denervation. De-efferented intrafusal fibres developed into distinct ultrastructural fibre types similar to those found in control muscles. The nuclear bag type had confluent myofibrils with ill-defined M lines and relatively few mitochondria. The nuclear chain type had discrete myofibrils with prominent M lines, numerous large mitochondria and a more developed sarcotubular system. The fibre type characteristics were sometimes blurred by disarranged cross striation, but they were clearly discernible in 59 out of 69 de-efferented fibres of 31 spindles investigated in the electron microscope. A sample of 220 de-efferented spindles from leg muscles of 6 rats was examined in the light microscope on transverse sections stained for ATPase activity. The difference in the ATPase activity among intrafusal fibre types was marked in about 70% spindles; in contrast to this, no distinct fibre types could be discerned in the population of extrafusal fibres which were stained rather uniformly. In de—efferented spindles-as in normal control spindlesnuclear chain fibres always exhibited high ATPase activity, whereas one of the nuclear bag fibres had low ATPase and the other either low or medium to high ATPase activity. However, the ATPase activity of de-efferented muscles was generally lower than that of normal muscles. It can be concluded that intrafusal fibres do acquire their fibre type characteristics after fusimotor denervation despite complete deprivation of nerve impulse activity during the postnatal period when intrafusal fibre types differentiate in normal spindles.
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  • 57
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    Keywords: Protonephridium ; Pomatoceros triqueter (Annelida, Polychaeta, Sedenta-ria) ; Terminal cell ; Channel cell ; Development
    Source: Springer Online Journal Archives 1860-2000
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    Notes: Summary During the development of the intermediate and late gastrula of Pomatoceros triqueter, the terminal and channel cells grow towards each other and form the protonephridium. They interdigitate through lateral microvilli. The junctions between the cells form filtration clefts, which are bridged by fibrils.
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    Cell & tissue research 137 (1973), S. 251-269 
    ISSN: 1432-0878
    Keywords: Synapse ; Development ; Spinal cord ; Amphibian
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An electron microscopical study has been made of the cervical spinal cord of Xenopus laevis embryos, from the time that the neural tube closes until the larvae were hatched and could swim. Sections of the whole cord were searched for intercellular junctions during this period. Two nonsynaptic types were found, the first were widely distributed puncta adherentia, the second were rare and similar to “gap” junctions. Membrane specializations with synaptic vesicles were first found when the neural folds had fused; “membrane-vesicle clusters” which looked like the presynaptic half of a synaptic junction were present, together with synaptic junctions lacking any postsynaptic membrane thickening or cytoplasm density. About four hours later, mature synaptic junctions with full thickening of the postsynaptic membrane, dense cytoplasm and striated or dense material in the synaptic cleft were present. Presynaptic mitochondria, dense-cored and flattened vesicles, fibre to fibre and fibre to cell body synapses were present from the first, as were synapses onto very fine dendrites which might be filopodia from dendritic growth cones. Synaptogenesis may start with the accumulation of vesicles in dense cytoplasm near a thickened cell membrane; the postsynaptic element becomes associated with this “membrane-vesicle cluster” and matures by increasing cleft and cytoplasmic density, and by membrane thickening.
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  • 59
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    Keywords: Hypothalamo-hypophysial system ; Development ; Monoamines ; Colour change ; Fluorescence microscopy
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    Notes: Summary In Xenopus laevis the development of hypothalamic monoaminergic cells was studied in relation to adaptation to background colour. The first melanophores appear at stage 33/34 (normal table of Nieuwkoop and Faber, 1956), gradually increasing in number. The melanine granules are dispersed throughout the cell, irrespective of the background colour. The dispersion apparently is caused by MSH released by the developing pars intermedia cells. Between stage 39 and stage 41, larvae placed on a white background changed colour from black to white due to aggregation of the melanine granules within the melanophores. With Falck's method for demonstrating monoamines, a small number of fluorescent cells was observed in the hypothalamus simultaneously with the first background-dependent colour change. These cells were arranged in a paired nucleus, bordering the third ventricle. Initially, the nucleus extends from 50 microns behind the optic chiasma to the lateral dilatations of the third ventricle; 8–10 hours later, similar cells were also found at the lateral dilatations and in the dorso-lateral part of the infundibular lobe. The cells have apical processes protruding in the ventricular lumen. Fluorescent axons, originating from the cells, were occasionally observed. Considering the above-mentioned results in combination with the electron microscopical data of Nyholm (1972), it is concluded that the MSH producing cells are under monoaminergic nervous control from the beginning of background colour adaptation.
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    Cell & tissue research 150 (1974), S. 481-492 
    ISSN: 1432-0878
    Keywords: Seminiferous tubule, ovine ; Lamina propria ; Development ; Endocrine factors ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the lamina propria in the ovine seminiferous tubule was studied from 54 days (postcoitum) fetuses up to sexual maturity. In young animals (aged about two months) the effect of hypophysectomy and/or hormones was also analyzed. Initially, large areas of the lamina propria already show signs of morphological differentiation. The non cellular component is a single or sometimes double lamella. Outwardly, the cellular component is represented by rounded connective tissue cells or by elongated cells, exhibiting 80 Å filaments in the cytoplasm and arranged in 3 to 4 layers. By the first week after birth, the non cellular component is formed by 8 to 10 lamellae and the cellular component shows typical contractile cells, the fibroblasts being now located only in the periphery. Basically, the same aspect is found in the adult ram, thus differing from the more extensively studied prototypes of lamina propria architecture of rodents or primates. In as much as the sheep lamina propria differentiates precociously, probably induced by fetal testicular hormones, it is relatively insensitive to hypophysectomy or hormonal substitution. Hypophysectomy and cyproterone acetate administration cause intracytoplasmic lipid deposition in the contractile cells, the other components being not changed. Some questions are raised concerning the role of this peculiar lamina propria in the function of the blood-testis barrier.
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    Cell & tissue research 151 (1974), S. 509-523 
    ISSN: 1432-0878
    Keywords: Gill ; Trout ; Secondary lamellae ; Development ; Light and electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A light and electron microscope study of secondary lamellae of trout developing at 10° C is described. Collagen is secreted by mesenchyme cells in the connective tissue of the developing gill filament. This becomes enclosed in infoldings around the peripheries of mesenchyme cells. These cells become aligned in a single plane within folds of basement membrane and epithelium. The basement membrane of opposite sides of the fold becomes connected by a thick layer of collagen. Blood spaces form around the margin of the fold, connecting afferent and efferent filament blood vessels. Endothelial granules form in cells lining the outer border of the marginal channel when blood flow begins. Rows of pillar cells separate from the proximal layer of mesenchyme cells as the secondary lamellae develops further. New secondary lamellae are added at the filament tips. At 28 days, the basement membrane consists of 2 layers, a fine fibrous layer and 5–15 orthogonally arranged layers of collagen fibres. By 31 days, the collagen is arranged at random and the layer is thinner. A clear layer is also present by 67 days. A multilayered epithelium containing mucous and chloride cells is present at 28 days. By 102 days, the secondary lamellae are covered by 2 layers of epithelial cells only. Chloride cells are present in much greater numbers in developing gills than in the adult.
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    Cell & tissue research 152 (1974), S. 13-30 
    ISSN: 1432-0878
    Keywords: Human fetal pineal gland ; Development ; Secretion ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the pineal gland of 18 human fetuses (crown-rump lengths 30–178 mm) was investigated. The pineal gland exhibits a pyramidal shape and consists of an anterior and posterior lobe. Only one parenchymal cell type, the pinealocyte, was observed. Few neuroblasts were seen between the pinealocytes and in the extended perivascular space. The pinealocytes possess all the organelles necessary for hormone synthesis. No specific secretory granule could be observed. The organ is abundantly vascularized and richly innervated. The morphology of the capillaries indicates the existence of a blood-brain barrier. The ultrastructure of the human fetal pineal gland suggests that the gland has a secretory function in early intrauterine life.
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    Cell & tissue research 109 (1970), S. 138-146 
    ISSN: 1432-0878
    Keywords: Insect muscles ; Development ; Microtubuli ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung In der indirekten Flugmuskulatur von Phormia terrae-novae kann die Entwicklung der Myofibrillen deutlich in eine Anlage- und eine Wachstums-Phase unterteilt werden. Zu Beginn der Wachstumsphase wurde Puppen eine Lösung von Colchicin in die rechte Metathoraxhälfte injiziert. Als Folge dieser Behandlung lösten sich zunächst die Mikrotubuli in der Flugmuskulatur auf. In späteren Entwicklungsstadien bildeten sich atypische Verzweigungen der Myofibrillen, die zu einer partiellen Desorientierung der kontraktilen Strukturen führten. Ein Mechanismus, der solche Störungen des Orientierungmusters in der Normalentwicklung möglicherweise verhindert, wird diskutiert.
    Notes: Summary In the blowfly Phormia terrae-novae the development of myofibrils of indirect flight muscles can be divided into periods of predisposition (anlage) and of growth. At the beginning of the growth period microtubules are disrupted by injection of colchicine. This disruption is followed by the formation of atypical ramifications of myofibrils at Z-discs leading to numerous disoriented myofibrils in late developmental stages. A possible mechanism preventing these alterations during normal development is discussed.
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    Cell & tissue research 110 (1970), S. 72-84 
    ISSN: 1432-0878
    Keywords: Lung cells ; Chick embryo ; Lamellar inclusions ; Ultrastructure ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Les pneumocytes granuleux, qui constituent l'un des principaux types cellulaires de l'épithélium pulmonaire, sont caractérisés par la présence de volumineuses inclusions osmiophiles lamellaires. Nous avons étudié l'apparition et l'origine de ces inclusions dans l'épithélium du poumon embryonnaire de Poulet, en l'examinant à différents stades du développement. Les premières inclusions lamellaires apparaissent dans le poumon de l'embryon de 16 jours. A ce stade, quelques lamelles concentriques entourent une zône centrale amorphe étendue; la périphérie des inclusions contient toujours de petites structures granulaires. Les jours suivants le nombre de cellules contenant des inclusions lamellaires augmente rapidement; en même temps, les lamelles deviennent plus nombreuses. A 19 jours, les inclusions lamellaires ont un aspect semblable à celui qu'elles ont dans les poumons d'animaux adultes. Dès l'apparition des ébauches pulmonaires, à 2 1/2 jours d'incubation, les cellules épithéliales contiennent des inclusions typiques: les inclusions granulaires. Ces organites sont caractérisés par un centre granulaire, qu'entouré un système membranaire. Ce système, simple chez le jeune embryon, évolue ensuite en se compliquant; chez l'embryon de 16 jours, il s'enroule en plusieurs couches autour de la masse centrale. Au moment où les premières inclusions lamellaires apparaissent, le nombre des inclusions granulaires augmente rapidement; on les trouve souvent étroitement associées à des vacuoles lipidiques. L'analyse des relations entre inclusions lamellaires, inclusions granulaires et vacuoles lipidiques suggère que l'inclusion lamellaire résulte de la collaboration entre une vacuole lipidique et plusieurs inclusions granulaires.
    Notes: Summary The granular pneumocytes, one of the main cellular types of the lung epithelium, are characterized by the presence of large osmiophilic lamellar inclusions. The appearance and origin of these inclusions has been studied in the epithelium of chick embryonic lung at different developmental stages. Lamellar inclusions are first seen in the lung of 16 day old embryos. At this stage, few concentric lamellae surround a large amorphous center; the periphery of the inclusions always contains small granular structures. In the following days, the number of cells containing these lamellar inclusions increases rapidly, while their lamellae progressively become more numerous. In 19 day old embryos, the lamellar inclusions are similar to those in the lungs of adult animals. From the earliest formation of the bronchial primordia, their epithelial cells contain a number of typical “granular” inclusions. These organelles are characterized by a granular center, enclosed in a membranous system. This structure becomes more complex as the embryo develops; in the 16 day old embryo, the multilayered membranous system coils around the granular center. At the time when lamellar inclusions first appear, granular inclusions increase rapidly in number and are often found in close association with lipidic vacuoles. The relationships between lamellar inclusions, granular inclusions and lipidic vacuoles are discussed. The evidence suggests that a lamellar inclusion arises from the cooperation of several granular inclusions and a lipidic vacuole.
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    Cell & tissue research 113 (1971), S. 558-563 
    ISSN: 1432-0878
    Keywords: Pterin layer ; Pigmentation ; Dermis ; Development ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of the pterin layer was investigated in both wild type Rana pipiens and Rana pipiens homozygous for the speckle mutant gene. No difference in morphology of the layer was noted between the wild type and mutant. The layer lines the outer surface of the stratum compactum of the dermis and separates this stratum from the stratum spongiosum. The pterin layer consists of extra-cellular material and contains membrane-bounded granules filled with fine spicules. Many of the spicules are somewhat similar in appearance to the initial calcification loci present in developing membrane bone. The layer first appears in the tadpole at approximately stage 14 (Taylor and Kollros, 1946); subsequent developmental stages are described.
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    Cell & tissue research 113 (1971), S. 157-173 
    ISSN: 1432-0878
    Keywords: Prostate ; Development ; Ultrastructure ; Rat
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    Topics: Biology , Medicine
    Notes: Summary The postnatal development of the rat prostate has been studied with the electron microscope. Major developmental changes begin during the second week after birth and involve organelles associated with the formation of secretions. The amount of granular endoplasmic reticulum and the size of the Golgi complex increase greatly. Large vacuoles that probably contain secretory material are formed, and the lumen of the prostatic acini appears to contain secreted material. Large lysosomes with polymorphic interiors are present as early as 10 days after birth, and they become numerous by the end of the third week. Differences in fine structure between the different lobes of the prostate are detectable in 10–14 day old rats. The subsequent differentiation of the granular endoplasmic reticulum into the forms characteristic of the different prostatic lobes is described. The initial changes in the prostate occur in advance of sexual maturity of the animal, and the adult appearance of the gland is attained by 4–5 weeks after birth.
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    Cell & tissue research 114 (1971), S. 546-556 
    ISSN: 1432-0878
    Keywords: Microvilli ; Small intestine ; Brush border ; Development ; Golgi apparatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Frage, auf welche Weise die Enterocyten des fetalen Rattendünndarms das für die Mikrovillibildung benötigte Membranmaterial liefern, wurde elektronenmikroskopisch untersucht. Es wird angenommen, daß hufeisenförmige Strukturen, die aus mit elektronendichtem Material bedeckten Elementarmembranen bestehen und möglicherweise Längsschnitten durch kappenförmige Gebilde entsprechen, in das apicale Plasmalemm eingebaut werden und für die Bildung der Mikrovillispitzen verantwortlich sind. Diese Annahme gründet sich in erster Linie auf die Feststellung eines nahezu identischen Durchmessers von „Hufeisen“ und Mikrovilli, auf die Lokalisation der „Hufeisen“ im Terminalgespinst und ihr zahlenmäßiges Verhalten während der Mikrovillibildung. Die „Hufeisen“ entstehen im Golgi-Apparat.
    Notes: Summary The origin of membranes required for the formation of microvilli has been investigated electronmicroscopically in enterocytes of fetal rat small intestine. It is assumed that horseshoe-like structures consisting of unit membranes covered with electron-dense material, which probably represent longitudinal sections through cap-like structures, are incorporated into the apical cell membrane and give rise to the tips of microvilli. This assumption is based chiefly on the almost identical diameters of “horseshoes” and microvilli, the localization of “horseshoes” in the terminal web, and the time of appearance and disappearance of “horseshoes” with regard to development of microvilli. There are indications that the “horseshoes” originate in the Golgi apparatus.
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    Cell & tissue research 115 (1971), S. 396-415 
    ISSN: 1432-0878
    Keywords: Human pineal organ ; Development ; Innervation ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This investigation is concerned with pineal organs of human embryos 60 to 150 days old. At every stage central nerve fibres enter the pineal organ by way of the habenular commissure, but are restricted to the pineal's proximal part. On about the 60th day of the development the sympathetic nervus conarii grows into the distal pole of the pineal organ from a dorso-caudal direction and plays the predominant part in the innervation of the pineal organ. After penetrating, it soon branches out and forms a network in the pineal tissue. Much later, not until the 5th embryonic month, sympathetic nerves appear accompanying the supplying vessels in the perivascular spaces. After a short time these nerves pierce the outer limiting basement membrane and penetrate the parenchyma. Towards the end of the 5th embryonic month the axons of the sympathetic nerves form varicosities containing clear and dense core vesicles. At this point large amounts of laminated granules appear primarily in cell processes, probably of pinealocytes. Isolated granules also occur in the varicosities of axons. The granules encountered here are most likely secretory granules.
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    Cell & tissue research 118 (1971), S. 579-592 
    ISSN: 1432-0878
    Keywords: Bye ; Innervation ; Adrenergic ; Development ; Manuals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of adrenergic nerves to the anterior eye segment was studied in human and guinea-pig embryos. Adrenergic terminals had already appeared in the earliest human embryos available (4–6 cm). They first appeared mainly in nerve trunks in the primitive chorioid, especially in the region of the developing ciliary body. Adrenergic nerves then grow into different structures of the eye as these develop, but typical terminals in contact with effector cells appeared late during the development, about the 25–30 cm stage. No adrenergic nerves were observed in the chamber angle. Corneal adrenergic nerves (also intraepithelial terminals) appeared much more frequently in embryos than in adults. No adrenergic neurons were observed in the retina. In the guinea-pig, the first adrenergic fibres were observed at about gestation day 35. The general principle of the development was very similar to that of the humans. At gestation day 45 to 50, the supply of adrenergic fibres was essentially that of the adult animal, except that the corneal adrenergic fibres were increasing until just before birth and that the adrenergic terminals of the chamber angle appeared shortly before term.
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    Cell & tissue research 119 (1971), S. 208-226 
    ISSN: 1432-0878
    Keywords: Median eminence ; Hypophysial portal vessels ; Pars distalis ; Ultrastructure ; Development
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    Notes: Summary Nerve fibres containing granular vesicles first appear in the median eminence of the rat on the 16th foetal day while secretory granules in the cells of the adenohypophysis are not present till the 17th foetal day. These observations suggest that the differentiation and early activity of pars distalis cells may depend on substances elaborated at nerve terminals in the median eminence. Although the loops of the primary plexus of portal vessels do not develop until the 4th postnatal day, substances released by nerve fibres in the neurohypophysis could reach the pars distalis through vessels already present at the 15th foetal day in the mesenchyme between the diencephalon and the adenohypophysis. This view is supported by the fact that the earliest cells to exhibit ultrastructural evidence of secretory activity are in the rostral pole of the pars distalis, the first region of the gland to become vascularized. The earliest granules to appear in the cells of the pars distalis correspond to those which are considered to contain mucoprotein hormones; somatotrophin type granules were seen only in postnatal tissues. The finding that, in the median eminence, the development of granular vesicles precedes that of agranular vesicles is discussed with reference to the times at which neurosecretory materials and monoamines become detectable in the region.
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  • 71
    ISSN: 1432-0878
    Keywords: SIF-cells ; Short adrenergic neurons ; Biogenic amines ; Osmiophilic granules ; Innervation of uterus ; Development
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    Notes: Summary A study was made of the ultrastructure of the paracervical (Frankenhäuser) ganglion of the newborn rat, using immersion fixation by glutaraldehyde (2.5%) followed by OsO4 (1%), or KMnO4 (3%) fixation. The cells containing dense—core vesicles were divided into three groups: (1) primitive sympathetic cells, (2) cells containing some dense-core vesicles 700–1100 Å in size and structurally resembling sympathetic neurons, called principal neurons, and (3) cells containing many dense-core vesicles with a larger, darker dense core, 800–2000 Å in diameter, called granule-containing cells. Using glutaraldehyde-osmium fixation, the principal neurons were further divided into dark and light cells on the basis of electron opacity of the cytoplasmic matrix. The granule-containing cells were believed to correspond to the small, intensely fluorescent cells (SIF-cells) previously described using the formaldehyde-induced fluorescence technique. On the basis of the amount of granules, the granulecontaining cells were classified as mature or maturing SIF-cells and as more primitive SIF-cells, and developing sympathicoblasts. The development of synapses in autonomic ganglia was discussed.
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    Cell & tissue research 127 (1972), S. 323-346 
    ISSN: 1432-0878
    Keywords: Thymus ; Frog ; Development ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary A study of the ultrastructure of the developing thymus of the leopard frog (Rana pipiens) revealed that the thymus had undergone all of the major changes which would persist through larval life and metamorphosis by the time that the animals had reached larval stage IV of Taylor and Kollros (1946). These changes included development of an outer, lymphoid cortical region and an inner, essentially nonlymphoid medulla; mitotic activity among lymphoid cell precursors and the formation of the first small lymphocytes; development of complex cysts containing PAS-positive material and the appearance of other signs of secretory activity among epithelial cells of the medulla; and differentiation of large myoid cells containing bundles of striated muscle fibrils. The changes are particularly noteworthy because they first appear during a period in which the animals are known to be developing the capacity to respond immunologically to allografts.
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    Cell & tissue research 128 (1972), S. 555-563 
    ISSN: 1432-0878
    Keywords: Astrocytes ; Capillaries ; Spinal cord ; Blood brain barrrier ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Glio-vascular relationships were studied in the developing rat cervical spinal cord with electron microscopy. Capillaries were first evident on the eleventh prenatal day and were surrounded by undifferentiated cells and neuroblasts separated from the capillary wall by a perivascular space. This space persisted until day thirteen, when basement membranes began to appear. Small cellular processes containing glycogen were visible adjacent to the capillary basement membrane beginning at day fifteen and became more prominent as development proceeded. The origin of these cellular processes was not apparent, but they were most likely collaterals of epithelial elements. In prenatal animals neuroblasts or neurons were in direct contact with the capillary basement membrane. Cells resembling adult astrocytes were first observed during the nineteenth day. Astrocytic processes completely invested the capillaries, separating them from neurons in the spinal cord of all postnatal animals.
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    Cell & tissue research 129 (1972), S. 278-289 
    ISSN: 1432-0878
    Keywords: Midgut epithelium ; Insects ; Development ; Metamorphosis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural alterations in the anterior midgut epithelium of the fly Calliphora were investigated by electron microscopy. Nine developmental stages, from late larval to late adult, were studied. During metamorphosis, a tube is formed by proliferation of undifferentiated cells residing in cell nests in the basal part of the larval epithelium. The process of microvillus formation is described and compared with that in the embryonic stage. Differences between larval and imaginal cells were found in the rate of microvillus formation and in the occurrence of dense vesicles. The formation of a basal labyrinth coincides roughly with microvillus formation. Glycogen deposits occur mainly in the pupal stage and are almost always absent after emergence. Epithelial crypts are formed in late pupae by modification of the existing layer of cells together with a localized development of muscle fibres. In the adult stage changes may take place in the form of the cell apex, which generally assumes a more pointed shape, and in the amount of osmiophilic material, aggregating almost exclusively in the supranuclear part of the cell.
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  • 75
    ISSN: 1432-0878
    Keywords: Hypophysis ; Rana temporaria ; Development ; Corticotropin cells, melanotropin cells ; Immunofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary During the embryonic and larval developmental stages of the frog, Rana temporaria L, anti-β 1–24, α 17–39 corticotropine, α and β MSH antibodies were used to define, with immunofluorescence technique, the appearence of corticotropic and melanotropic cells. A very small number of fluorescent corticotropic cells appears for the first time during the embryonic stage (10 mm), just before the differentiation of the pars intermedia. The cells are small, their large nucleus is surrounded by a fine rim of fluorescent cytoplasm. During premetamorphic stage, the anti-ACTH antibodies (anti-β 1–24 and anti-α 17–39 corticotropine) reveal more fluorescent cells in the whole pars distalis. The pars intermedia cells can also be visualized by both antisera. At the end of prometamorphosis and during climax the corticotropic cells show a more precise localization. As in adult frog pars distalis, they are concentrated in the rostral half of the lobe. With the same technique anti-α and β MSH antibodies reveal only the cells of the pars intermedia. No other cell type of the pars distalis reacts with these antibodies. This technique has the advantage to show that the ACTH and the MSH cells appear very early during the embryonic life.
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  • 76
    ISSN: 1432-0878
    Keywords: Sympathetic neurons ; Chromaffin cells ; SIP cells (Newborn rat) ; Development ; Administration of hydrocortisone ; Stretch preparations ; Fluorescence microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Air-dried stretch preparations were used to study adrenergic nerve fibres and catecholamine-containing cells with the formaldehyde-induced fluorescence method in the abdominal tissue block containing the para-aortic paraganglia, in the neurovascular structures of the cervical region including the carotid body, in the bladder, in the ileum, in the mesentery, in the vagus nerve and in the sympathetic ganglia of 5- or 15-day-old rats. The adrenergic nerves and the catecholamine-containing cells were well preserved and showed little or no diffusion of amines. While most intensely fluorescent cells of the main para-aortic body disappeared during the first two postnatal weeks, some such cells survived and they showed long, slender fluorescent processes. Administration of 20 mg/kg of hydrocortisone acetate daily for 5 days after birth caused a striking increase in the number and size of the clusters of the intensely fluorescent cells in the organ of Zuckerkandl, in the sympathetic ganglia and in the bladder, as well as an increase in the fluorescence intensity of the carotid body. In rats treated with hydrocortisone for 5 days and left to recover for 10 days an increased fluorescence was still observed. However, in the organ of Zuckerkandl the intensely fluorescent cells of hydrocortisone-treated 15-day-old rats showed less processes than those of the control rats of the same age.
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  • 77
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    Cell & tissue research 110 (1970), S. 173-184 
    ISSN: 1432-0878
    Keywords: Submandibular gland ; Secretory units ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of the secretory units of the mouse submandibular gland was studied according to the developmental sequence. The embryonic submandibular gland consists of terminal tubules and ducts. Myoepithelium is associated only with the terminal tubules, and the cells of the primary intercalated ducts show characteristics of the young striated duct cells. The major changes shortly after birth consist of: 1) opening of the secretory lumina, 2) increasing rough ER and its altered configuration, 3) dilatation of Golgi cisternae and 4) changes in the granular structure. These findings suggest that the salivary secretion first occurs after birth, and acinar differentiation or transformation of the secretory cells of the terminal tubules is induced and profoundly affected by the commencement of the secretory activity. In the intercalated ducts this process is somehow inhibited, and the granular cells found in the adult can be considered as the remnants of the secretory cells of the terminal tubules.
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  • 78
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    Cell & tissue research 110 (1970), S. 401-443 
    ISSN: 1432-0878
    Keywords: Integument ; Oenocytes ; Structure ; Development ; Culex pipiens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung 1. Struktur und Entwicklung des Integuments und der larvalen Oenocyten während des Puppen- und pharaten Imaginalstadiums von Culex pipiens L. (Dipt.) werden beschrieben. 2. Auf- und Abbau der pupalen und die Anlage der imaginalen Cuticula verlaufen innerhalb enger zeitlicher Grenzen. 3. Beim Abbau der pupalen Endocuticula erscheint immer die Lamina der jeweils innersten Lamelle als „Häutungsmembran“. 4. Die Oenocyten sind durch ihr agranuläres, tubuläres endoplasmatisches Retikulum (ATER) und dessen Veränderungen charakterisiert. Die Struktur der Oenocyten gleicht der steroidproduzierender Wirbeltierzellen. 5. Das Aussehen der Oenocyten ändert sich kurz nach der Puppenhäutung hauptsächlich durch die kontinuierliche Zunahme von sog. Lipidvesikeln. Diese Vesikel entstehen durch Erweiterungen tubulärer Elemente des agranulären endoplasmatischen Retikulums. 6. Im Lichtmikroskop erscheinen diese Veränderungen als Kanalstrukturen („Sekretionsphase“) kurz nach der Puppenhäutung; später nimmt das Cytoplasma eine mehr vakuoläre Struktur an („Degenerationsphase“). 7. Mit Sudanschwarz B und Sudan III/IV lassen sich Lipide in den Erweiterungen der Tubuli des agranulären endoplasmatischen Retikulums (= Lipidvesikel) nachweisen. Nach Osmiumsäure-Fixierung sind sie nicht darstellbar. 8. Kurz vor der Imaginalhäutung kommt es in den Oenocyten zu massiver Autophagie. Dieser folgt ein Abbau des ATER und anderer Teile des Cytoplasmas. 9. Es gibt keinen Hinweis, daß die Oenocyten direkt für die Bildung der epicuticularen Lipide verantwortlich sind.
    Notes: Summary 1. Structure and development of the integument and the larval oenocytes during the pupal and pharate imaginai stage of Culex pipiens L. (Dipt.) are described. 2. Formation and digestion of the pupal cuticle and the formation of the imaginai cuticle take place within temporarily fixed limits. 3. While the pupal endocuticle is digested the lamina of the at times innermost lamella appears as a “ecdysial membrane”. 4. The oenocytes are characterized by their agranular, tubular endoplasmic reticulum (ATER) and its changes. The structure of the oenocytes is comparable to that of vertebrate cells engaged in steroid hormone synthesis. 5. The morphology of the oenocytes shortly after pupal ecdysis changes mainly by the continual raising of so called lipid vesicles. These vesicles arise from dilatations of tubular elements of the agranular endoplasmic reticulum. 6. Studied under the light microscope these changes appear as channel structures (“secretory phase”) shortly after pupal ecdysis; later on the cytoplasma becomes vacuolar in structure (“degeneration phase”). 7. By staining with Sudan black B and Sudan III/IV lipids can be demonstrated in dilatations of the tubules of the agranular endoplasmic reticulum. However they do not stain after fixation with osmium tetroxide. 8. In the oenocytes massive autophagy takes place just before imaginai ecdysis. It is followed by breakdown of the ATER and other parts of the cytoplasma. 9. There is no evidence that the oenocytes are directly responsible for the formation of epicuticular lipids.
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  • 79
    ISSN: 1432-0878
    Keywords: Synaptic vesicles ; Development ; Golgi apparatus ; Smooth endoplasmic reticulum ; Zinc iodide-osmium technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Routine electron microscopy and a zinc iodide-osmium tetroxide technique (ZIO), recently found to be specific for synaptic vesicles, were used to study the origin of synaptic vesicles during postnatal development in the lumbosacral enlargement of the albino rat. In immature nervous tissue, a large number of vesicles, indistinguishable from synaptic vesicles (S vesicles), were found in the Golgi apparatus and in different portions of the axon where they were often intermingled with elements of the smooth endoplasmic reticulum (SER). Ten to twenty percent of these S vesicles within the Golgi apparatus as well as the majority of these vesicles in all parts of the axon were positive to ZIO. Much of the SER in axons was also positive. The number of vesicles and elements of the SER showed some decrease in the non-terminal portion of axons on day 21 and even more of a decrease in adult neurons. These data suggest that synaptic vesicles are produced in the Golgi apparatus and SER in immature neurons. The decrease in S vesicles and SER in adult neurons suggests a drop in synaptic vesicle production after synaptogenesis has ended. In addition, the material that has been studied shows that ZIO staining is not limited to synaptic vesicles during development since oligodendroglia and endothelial cells are also stained during this period.
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  • 80
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    Cell & tissue research 124 (1972), S. 433-444 
    ISSN: 1432-0878
    Keywords: Insect ; Fat body ; Development ; Protein body ; Electron microscopy ; Histochemistry ; Lipoprotein ; Cytology ; Lipid globule ; Silkworm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A developmental study at the electron microscopic level was conducted of the fat body cells of Hyalophora cecropia (L.). During the last larval instar the fat body increases in volume and the cells exhibit a well developed rough endoplasmic reticulum and protein bodies of diverse sizes. In the pupal fat body, the protein bodies appear to be enclosed by a double membrane and contain glycogen granules, ribosomes and mitochondrion-like structures. In addition, there are large lipid globules, cytolysomes and rough endoplasmic reticulum. The ultrastructure of the protein bodies suggests the development of large bodies by fusion of smaller protein bodies. Changes in fat body cell ultrastructure were followed during adult development and cytological evidence was obtained for the depletion of protein, glycogen and lipid in the female during this period. The female adult fat body cell contains free ribosomes, protein bodies, many mitochondria, a few lipid globules and glycogen granules. The male moth fat body cells have many mitochondria, a few glycogen granules, essentially no protein bodies, but an abundance of large lipid globules. Studies on the influence of egg maturation on the morphology of the fat body of Hyalophora gloveri (L.) revealed that ovariectomy of pupae yielded adults having more fat body than normal females, and that the fat body cells of the ovariectomized animals contained more glycogen, lipid and protein. Male pupae receiving ovarian implants developed into adults containing eggs and possessed more fat body than normal females but less than normal males. Very few glycogen granules were found in the fat body cells of normal males or males with implanted ovaries.
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  • 81
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    Cell & tissue research 129 (1972), S. 217-236 
    ISSN: 1432-0878
    Keywords: Olfactory sensilla ; Insects ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung 1. 1. Der cuticuläre Apparat der basiconischen Sensillen von Necrophorus wird von 4 Zellen gebildet. Hüllzelle 1 bildet die Dendritenscheide, die trichogene Zelle den von Poren durchsetzten Teil des Haares, die tormogene Zelle die porenfreie Haarbasis und Hüllzelle 4 Sockel und Ringwall des Sensillums. 2. 2. Die Entwicklung der Haaranlage wird durch einen Wachstumsschub des von einer Scheide umgebenen Dendriten eingeleitet. Dieser Wachstumsschub ist der Längenzunahme des Dendriten während der Häutung bei Hemimetabolen homolog. 3. 3. Die trichogene Zelle umschließt den Dendriten nur bis zu 2 μ oberhalb der Epitheloberfläche und wächst dann neben ihm zur vollen Länge des künftigen Haares aus. Mit Abscheidung der Cuticulinschicht degeneriert das freie Ende von Dendrit und Scheide. 4. 4. Die Anlage des Poren-Tubulus-Systems beginnt mit der Abscheidung der Cuticulinschicht. Bei Erreichen von ca. 30% der Haarwandstärke sind auch die Porentubuli ausgebildet. Der äußere Liquorraum entsteht durch Zurückweichen der trichogenen Zelle aus dem neu gebildeten Haar. Der Dendrit wächst innerhalb der sich zurückziehenden trichogenen Zelle in das Haar ein. Wenige Stunden nach dem Schlüpfen beginnt sich der Dendrit durch Vesikulierung und anschließende Vesikelfusion in ca. 50 Äste aufzuspalten.
    Notes: Summary 1. 1. The cuticular apparatus of the basiconic sensilla in Necrophorus is built up by four cells: the enveloping cell No. 1 secretes the dendritic sheath, the trichogen cell produces the part of the hair with pores, the tormogen cell the hairbase without pores, and the enveloping cell No. 4 produces the base and the ringwall of the sensillum. 2. 2. The development of the hair starts with the growth of the sheathed dendrite. This growth is homologue to the increase in length of the dendrite during moulting in hemimetabole insects. 3. 3. The trichogen cell surrounds the dendrite only up to 2 μ distal of the epithelial surface and then grows beside the dendrite to the full length of the future hair. After having secreted the cuticulin layer the free ends of sheath and dendrite degenerate. 4. 4. The development of the pore tubules system begins with the secretion of the cuticulin layer. When the hairwall has reached 30% of its thickness the pore tubules are fully developed. The outer liquor space is formed by withdrawal of the trichogen cell from the newly built hair. The dendrite grows into the hair inside the retreating trichogen cell. Few hours after emerging from the pupa the dendrite begins to split into about 50 branches: between the microtubules of the dendrite many vesicles arise which then fuse into continuous interspaces.
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  • 82
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    Cell & tissue research 136 (1973), S. 511-520 
    ISSN: 1432-0878
    Keywords: Muscle spindle ; Sensory ending ; Rat ; Development ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A fine structural study of sternothyroid muscle spindles of young adult rat demonstrates the rare occurrence of unique nerve endings. These endings are situated in the juxta-equatorial region of nuclear-bag fibers, adjacent to the annulo-spiral sensory endings. They consist of a bundle of terminal axons less than 0.3 μ in diameter and appear to be disposed nearly longitudinally to the axis of the intrafusal fibers. Whereas, the annulo-spiral endings consist of a single axon, coiling around the intrafusal fibers. Transverse sections of these muscle spindles reveal these unique endings scattered around the muscle fibers, fitting into depressions on their surface. The innermost axons directly face the muscle surface and are separated by a narrow gap less than 200 Å in width. No Schwann cell process appears to be associated with these endings. From their unique multi-axonal composition, these endings are termed “bundled endings”. Investigations of developing muscle spindles show the occasional presence of a similar multi-axonal composition of sensory endings in perinatal rats. It is suggested that “bundled endings” are sensory in nature, carrying an immature feature over to adult life.
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  • 83
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    Cell & tissue research 140 (1973), S. 145-167 
    ISSN: 1432-0878
    Keywords: Macroglia ; Microglia ; Spinal Cord ; Monkey ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An electron-microscopic study has been made of the glial cells in the developing lateral funiculus of the cervical spinal cord in fetal rhesus monkeys. The various macroglial cell types, their precursor cells, and microglia are discussed in detail. An astrocytic lineage is proposed in which glioblasts present in the lateral funiculus give rise to astroblasts that then develop into mature astrocytes. Oligoblasts apparently migrate into the lateral funiculus as such and develop into active oligocytes. The active oligocytes become most predominant during the initial stages of myelinogenesis and are in direct continuity with developing myelin. The active oligocytes develop into mature oligocytes after myelination is completed. Microglia cells are present throughout development as three forms; resting microglia, globose microglia, and active microglia. The globose and active microglia predominates at specific times early in development when degeneration of apparent neuronal processes is taking place. The microglia cells are characterized by dense nuclear chromatin clumps, lipid inclusion bodies, dense vesicles, and, often, intracellular debris.
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  • 84
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    Cell & tissue research 140 (1973), S. 203-216 
    ISSN: 1432-0878
    Keywords: Synapses ; Development ; Chick embryo ; Cell culture ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    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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  • 85
    ISSN: 1432-0878
    Keywords: Neuromuscular junction ; Development ; Cholinesterases ; Axonal transport, Neurotubules, Colchicine, Vinblastine ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Colchicine (0.1 M) or vinblastine (0.01 M) was locally applied on the sciatic nerves of newborn rats. Both colchicine and vinblastine caused reversible disappearance of axonal neurotubules and appearance of increased amounts of neurofilaments at the site of application. Subsequent morphogenesis of myoneural junctions in the tibialis anterior muscle was studied after histochemical demonstration of acetylcholinesterase (AChE; E.C. 3.1.1.7) and non-specific cholinesterase (Ns. ChE; E.C. 3.1.1.8) activity in the myoneural area. Development of the postsynaptic muscle plasma membrane of the myoneural junction was arrested in the ipsilateral, but not in the contralateral control side, for a period of about three weeks following treatment with the test substances. After this delay the myoneural morphogenesis continued normally and neurotubules were seen in the axoplasm. Since disruption of neurotubules is likely to cause blockage of the intratubular axoplasmic transport system, it seems possible that the neurotrophic influence responsible for the development of the postsynaptic muscle membrane is mediated through a secretory product transported along axons intratubularly to the nerve endings.
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  • 86
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    Keywords: Pars tuberalis ; Rat ; Development ; Secretion ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of the pars tuberalis was studied in the rat fetus from 13 days of gestation to 6 weeks after birth. After the closure of Rathke's pouch, the pars tuberalis anlage is clearly distinguishable from the anlagen of the partes intermedia and distalis. It comprises the entire basal portion of the adenohypophysial anlage; the limit between the anlagen of the pars tuberalis and the pars distalis is defined by Atwell's recess, i.e. the pathway taken by the hypophysial vessels coming from the vascular plexus of the median eminence. At 14 days the pars tuberalis cells are characterized by the presence of glycogen which persists in the adult. Their secretory differentiation (elaboration of granules with a diameter of 100–120 nm) is obvious at 15 days of gestation. It therefore, clearly precedes that of the other hypophysial cell types. Its functional differentiation takes place well before its adhesion to the primary vascular plexus of the portal system. Cystic formations appear just before birth in the pars tuberalis, much later than those of the pars distalis. These observations on the development of the pars tuberalis, together with previous observations on the adult PT in various species, showing that the specific glandular cells of the pars tuberalis are cytologically different from all known adenohypophysial cell types, seem to indicate a specific endocrine function of this lobe.
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    Cell & tissue research 147 (1974), S. 313-324 
    ISSN: 1432-0878
    Keywords: Chordotonal organ ; Teleogryllus commodus ; Hearing ; Structure ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The anatomical development of the tympanal organ, the tracheal system and the tympana of Teleogryllus commodus is described. The tympanal organ is undifferentiated until instar 3 when the first scolopales appear. The organ develops in a proximo-distal direction but the more distal groups begin to form before the proximal groups are complete. All groups of scolopidia are represented in instar 7 but numbers of scolopidia continue to increase until the adult stage. Scolopales and scolopale cells are first formed at less than adult size and increase in size during subsequent instars. The subgenual organ is present in instar 1 and is complete in instar 4. The posterior and anterior tympanal trachease develop respectively from the tracheal trunk and tracheal branch, which are present from instar 2. These remain as simple, unconnected tubes until instar 7 and begin to show the adult form during instars 8 and 9, finally enlarging in conjunction with the tympana at the last two moults. The tympana first appear as hairless areas of cuticle in the larval stages: the posterior tympanum in instar 8 and anterior tympanum in instar 10, but the translucent appearance of the adult tympana is not present before the final moult.
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    Cell & tissue research 105 (1970), S. 33-54 
    ISSN: 1432-0878
    Keywords: Microsporidian ; Development ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Vegetative growth of Nosema sp. occurs within the gut submucosal cells of Callinectes sapidus. Vegetative cell morphology is dominated by profiles of endoplasmic reticulum, numerous free ribosomes and aggregates of vesicles enclosed by a membranous sac. The dikaryotic vegetative cell is the earliest stage found in the target area for sporogenesis, the sarcoplasm of the striated muscle cell. The next obvious stage is the sporoblast mother cell; it undergoes karyokinesis without breakdown of the nuclear envelope. Intranuclear mitotic microtubules extend from the chromosomes to the intact nuclear envelope. After repeated nuclear divisions, the sporoblast mother cell undergoes delayed cytokinesis and a series of sporoblast progeny develops. The polar filament is the first visually apparent system to develop during sporogenesis. It appears to be of dual origin: (1) the central core component is condensed in Golgi-like saccules, and (2) the envelopes around the core originate from the endoplasmic reticulum. The polaroplast, which forms after early polar filament development, appears to originate as an elaboration of the endoplasmic reticulum.
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    Cell & tissue research 104 (1970), S. 19-28 
    ISSN: 1432-0878
    Keywords: Pineal complex ; Development ; Aves, Columbidae ; Accessory evaginations ; Pineal tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Study of the pineal complex of several Columbiformes demonstrates: a) the presence, in embryos, of numerous evaginations of the diencephalic roof; b) the presence, in adults, of a parenchymal accessory structure, probably a remnant of one or more secondary evaginations; c) the variability, among specimens, of the diencephalic course of the pineal tract fibers; d) the predominant asymmetry of the basal attachment of the pineal stalk to the left of the mid-line.
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  • 90
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    Cell & tissue research 104 (1970), S. 517-529 
    ISSN: 1432-0878
    Keywords: Hypothalamo-hypophysial system ; Neurosecretion ; Guinea pig ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The time and place of occurrence of the neurosecretory substance in the hypothalamo-neurohypophysial system of the guinea pig during embryogenesis have been investigated. Use is made of the luminiscence of neurosecretion stained with paraldehydefuchsin when observed in a dark field. It is established that the neurosecretory material occurs first in some cells of the supraoptic nucleus about the 39th–40th day of intrauterine development. In the paraventricular nucleus it is observed about the 44th–45th day. At that time it is seen also in Eminentia mediana and in the neurohypophysis. In the latter, however, it is in a smaller amount than in the areas situated above it. These results are discussed in connection with the transport theory of Bargmann and Scharrer.
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    Cell & tissue research 104 (1970), S. 405-418 
    ISSN: 1432-0878
    Keywords: Retina ; Intercellular junctions ; Development ; Histogenesis ; Neurogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of intercellular junctions in the neural retina of the chick embryo between the seventh and nineteenth day of incubation has been studied. The main findings are: 1. The zonulae adhaerentes, which make up the outer limiting membrane of the adult retina, are present throughout the period of development covered by this study. 2. Small intercellular junctions of the macula adhaerens diminuta type appear in large numbers in the plexiform layers of the retina of 10 days incubation and are retained throughout development. 3. Synapse-like structures appear in the inner plexiform layer of the retina after 14 days of incubation. The possible relevance of these intercellular junctions to retinal morphogenesis is discussed.
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    Cell & tissue research 104 (1970), S. 165-177 
    ISSN: 1432-0878
    Keywords: Development ; Neurons ; Retina ; Xenopus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary All cells in the optic vesicle of Xenopus embryos from stages 27 to 31 have the same ultrastructure. They are elongated and appear to extend from the internal to the external surfaces of the optic vesicle. They are bound together by terminal bars at the internal (lumen) margin, have microvilli and a cilium on the internal margin, and are covered with a basement membrane on the external margin. Their cytoplasm contains abundant free ribosomes, polysomes, mitochondria, yolk and lipid inclusions, and sparse endoplasmic reticulum. Although other studies have shown that retinal ganglion cells originate at stages 29–30 and have their central connections determined before stage 31, these events could not be correlated with any ultrastructural changes. The first sign of differentiation in retinal cells was an increase in endoplasmic reticulum and Golgi apparatus at stage 32. Microtubules and microfilaments appeared at stage 33 in association with the first axonal outgrowth from retinal ganglion cells. Cytodifferentiation proceeded gradually until large areas of Nissl substance had developed by stage 35. At larval stage 48 the ganglion cells resembled those in the adult.
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    Cell & tissue research 105 (1970), S. 515-525 
    ISSN: 1432-0878
    Keywords: Cuticle ; Rotifer ; Development ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructural studies of developing Asplanchna brightwelli embryos support the following hypothetical scheme of cuticle formation. First the external hypodermal membrane invaginates, and deposition of a dense intracellular layer commences next to this membrane. Then the rough endoplasmic reticulum synthesizes fibrous protein which is transferred to the Golgi complex. Here polysaccharide is synthesized and added to the protein, and the resulting filamentous complex is enclosed in large irregularly shaped vesicles which bud off from the Golgi elements. Maturation of the filamentous material to condensed cuticle material occurs as the vesicles move to the invaginations. Each vesicle fuses with an invagination, thus forming a hypodermal bulb; then the cuticle material is discharged through the neck of the bulb to its extracellular location. After the bulbs are formed, new, smaller, spherical vesicles begin to bud off from the Golgi elements. They too contain the filamentous complex which is refined to condensed cuticle material as the vesicles near the bulb. These vesicles fuse with the hypodermal bulbs contributing the cuticle and membrane necessary for the growth of the hypodermis of the embryo and newborn animal. Ruthenium red staining has confirmed that the cuticle consists of glycoprotein.
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 95
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 96
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 97
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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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  • 98
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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.
    Source: Springer Online Journal Archives 1860-2000
    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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  • 99
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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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  • 100
    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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