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  • Rat  (123)
  • pharmacokinetics  (48)
  • Inversion
  • Springer  (171)
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  • 1970-1974  (172)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 14 (1974), S. 283-289 
    ISSN: 1432-0827
    Keywords: Sodium fluoride ; Osteoporosis ; Bone ; Strength ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'utilisation thérapeutique de fluorure de sodium a été recommandée dans le traitement de diverses maladies osseuses ostéopéniques. Cet emploi est basé principalement sur les effects ostéosclérotiques bien connus du fluorure de sodium, mais on connait mal son effet sur la force de résistance osseuse. L'influence de diverses concentrations de fluorure de sodium sur la force de résistance osseuse de jeunes rats soumis à des régimes riches et pauvres en calcium a été étudiée. L'administration de fluorure de sodium augmente le diamètre osseux, indiquant une stimulation de la formation de l'os périosté, mais la force de résistance osseuse est réduite ou non modifiée par l'ingestion de fluor.
    Abstract: Zusammenfassung Die therapeutische Verwendung von Natriumfluorid ist für eine Anzahl von Knochenmangel-Krankheiten empfohlen worden. Die Empfehlungen basieren hauptsächlich auf den bekannten osteosklerotischen Wirkungen von Natriumfluorid; über dessen Effekt auf die Knochenstärke ist wenig bekannt. In dieser Arbeit wurde der Einfluß verschiedener Konzentrationen von Natriumfluorid auf die Knochenstärken von wachsenden Ratten mit hoher und niederer Calciumeinnahme untersucht. Die Verabreichung von Natriumfluorid erhöhte den Knochendurchmesser, was auf eine Stimulierung der Periostbildung hinwies, die Knochenstärke wurde jedoch durch Fluorideinnahme herabgesetzt oder nicht beeinflußt.
    Notes: Abstract The therapeutic use of sodium fluoride has been recommended in a variety of osteopenic bone diseases. The recommendations are based mainly on the known osteosclerotic effects of sodium fluoride and little information is available as to its effect on bone strength. The influence of various concentrations of sodium fluoride on bone strength in growing rats on high and low calcium diets was studied. The administration of sodium fluoride increased bone diameter, indicating stimulation of periosteal bone formation, but bone strength was reduced or not affected by fluoride ingestion.
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  • 2
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    Springer
    European journal of clinical pharmacology 7 (1974), S. 407-414 
    ISSN: 1432-1041
    Keywords: Diuretic ; indapamide ; human pharmacology ; toxicology ; pharmacokinetics ; TLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na+, K+ and Cl− and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca2+, Mg2+ and PO 4 3− rose in spite of a fall in urinary concentrations of these ions. The Ca2+ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.
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  • 3
    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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  • 4
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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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  • 5
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    European journal of clinical pharmacology 7 (1974), S. 375-380 
    ISSN: 1432-1041
    Keywords: Tranexamic acid ; pharmacokinetics ; man ; antifibrinolytic agents ; renal clearance ; two-compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tranexamic acid has been investigated in two healthy volunteers. The behaviour of the drug can be described in terms of a two compartment open model; the disposition (biological) half-life was 2.7 h and 1.9 h, respectively. In five normal volunteers the mean total recovery in urine 48 h after dosing was 94.8%. The renal clearance in the two subjects, adjusted to 1.73 m2 body surface area, was 135 and 132 ml/min/1.73 m2, respectively, indicating that tranexamic acid is eliminated by glomerular filtration and that neither tubular excretion nor absorption takes place.
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  • 6
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    European journal of clinical pharmacology 7 (1974), S. 381-385 
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; plasma half-life ; gas chromatographic analysis ; intra-individual variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intra-individual variability in the plasma half-life of phenazone has been studied in 16 healthy, young volunteers. Phenazone was analysed by a simple gas chromatographic method, which is specific in relation to known metabolites; 4′-methylphenazone was employed as the internal standard. Phenazone was given on two occasions, two or three months apart, in oral doses of 10 mg/kg. The plasma half-life determined from five time points was 10.9±1.5 h and 11.2±1.3 h respectively, on the two occasions. The mean intra-individual variability (0.86 h) was close to the methodological error of 4%.
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  • 7
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    European journal of clinical pharmacology 7 (1974), S. 25-29 
    ISSN: 1432-1041
    Keywords: Pindolol ; uraemia ; pharmacokinetics ; β-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of pindolol in 25 patients with various degrees of renal failure has been studied after an intravenous dose of 3 mg. A linear correlation was not found between the elimination rate of pindolol and the endogenous creatinine clearance, and the half-life of the unchanged drug was independent of the severity of the renal failure. This implies greater metabolism of pindolol in anuric patients and the extrarenal elimination rate constantk mwas increased. Three patients with severe renal failure were given 3 mg14C-pindolol. They showed almost constant plasma levels of radio-activity for 6 h and then slow excretion with a half-life of 48 h, because of accumulation of metabolites in the blood. Up to 90% of the metabolites are glucuronides and sulphates which have no beta-blocking or other clinical activity. Thus, to produce beta-adrenergic blockade the same dose of indolol is required in healthy patients as in those with uraemia.
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  • 8
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    European journal of clinical pharmacology 7 (1974), S. 59-60 
    ISSN: 1432-1041
    Keywords: Pizotifen ; isonicotinylhydrazine ; orexigen ; tuberculosis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pizotifen (BC 105) has an orexigenic effect in patients with pulmonary tuberculosis. As these cases are often treated with isonicotinylhydrazine (INH), any effect of one of these drugs on the absorption of the other has been examined in a cross-over study in 8 healthy male volunteers. No difference was found between the absorption of INH given alone or together with pizotifen. It should be safe, therefore, to employ the combination of the orexigenic drug and INH in the treatment of tuberculosis as there will be no change in the concentration of therapeutic drug achieved.
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  • 9
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    European journal of clinical pharmacology 7 (1974), S. 31-37 
    ISSN: 1432-1041
    Keywords: Diphenylhydantoin ; uraemia ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diphenylhydantoin (2 mg/kg) was infused intravenously in four uraemic patients and four healthy volunteers and its plasma concentration measured during and after the infusion. The plasma concentrations were considerably lower in the uraemic subjects and the apparent volume of distribution was higher. These observations could be explained by the lower plasma protein binding of diphenylhydantoin in the uraemics. The overall elimination rate constant β was greater (shorter half-life) in the uraemic patients. This difference could not be explained by reduced plasma protein binding, but it might be due to induction of diphenylhydantoin metabolism in the uraemic state. it is concluded that monitoring of the plasma levels of drugs in uraemic patients should be combined with determination of the extent to which the compounds are bound to plasma proteins.
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  • 10
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    European journal of clinical pharmacology 7 (1974), S. 51-58 
    ISSN: 1432-1041
    Keywords: Rifampicin ; plasma level ; pleural fluid concentration ; microbiological assay ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of rifampicin (RMP) were given to 31 patients with pleural effusions of various aetiologies. The concentrations of RMP and its active metabolites in pleural fluid and plasma were determined by an agar diffusion method using paper discs as diffusion centres. The plasma concentrations reached a peak within 3 h and then declined monoexponentially; in pleural fluid, RMP concentration rose slowly to reach a plateau that lasted for several hours. There were marked differences between subjects in the observed concentrations of RMP. During the first 12 h the plasma levels exceeded those in pleural fluid, but after 24 h the concentration of RMP in pleural fluid was higher than in plasma. If multiple oral doses of RMP 10 mg/kg b. w. are given every 24 h, as is common in the treatment of tuberculosis, therapeutic concentrations may be expected in pleural fluid for the major part of each day.
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  • 11
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    European journal of clinical pharmacology 7 (1974), S. 17-24 
    ISSN: 1432-1041
    Keywords: Pindolol ; beta-blockade ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of absorption, distribution and excretion of pindolol have been investigated in 17 volunteers after an oral dose or intravenous infusion of 5 mg. The calculated absorption was 92%. The time course of the plasma levels appeared to follow first order kinetics with an apparent half life of 3.6 (oral) and 3.1 (i.v.) hours. The cumulative urinary excretion att=∞ was 36.1% and 39.2% of the dose administered, respectively, indicating extensive metabolism of the drug. The distribution volume was 136 l. Peak plasma levels were found 80 min after oral administration and they showed up to 4-fold variation after identical doses. Renal clearance was 216 ml×min−1 and total clearance was 483 ml×min−1. In plasma 57% of pindolol was bound to protein.
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  • 12
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    European journal of clinical pharmacology 7 (1974), S. 119-124 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; phenytoin ; diphenylhydantoin ; bioavailability ; generic inequivalence ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels of phenytoin (diphenylhydantoin, DPH) in epileptic patients were significantly higher after treatment with either of two preparations containing the sodium salt of DPH, than after treatment with the same dose of the free acid. This was confirmed in both short and long term studies, and in the latter increased plasma levels of DPH were accompanied by better control of generalized seizures. The degree of acute side-effects in 6 out of 10 patients whose treatment was changed from DPH-acid to DPH-sodium was proportional to the plasma level of DPH; the latter varied from 22.8 to 34.9 µg/ml in affected patients. After a single oral dose in healthy volunteers, the sodium salt of DPH showed much better bioavailability than the free acid. The differences in bioavailability in patients and volunteers probably depended on differences in particle size in the preparations of the sodium salt of DPH and its free acid. The excipient, lactose or starch, did not seem to affect the bioavailability of the two formulations of sodium-DPH.
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  • 13
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    European journal of clinical pharmacology 7 (1974), S. 217-225 
    ISSN: 1432-1041
    Keywords: Rifampicin ; p-aminosalicylic acid ; drug interaction ; isoniazid ; pharmacokinetics ; antituberculous therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of rifampicin (10 mg/kg body weight), p-aminosalicylic acid (0.2 g/kg), isoniazid (10 mg/kg), or rifampicin and either p-aminosalicylic acid or isoniazid, were given to 69 tuberculous patients with normal renal and hepatic function. Ten-fold interindividual differences were observed in the peak serum concentrations and half-lives of rifampicin; its half-life was reduced from 4.3 h after the first dose to 3.1 h after the third dose, possibly due to self-induction of its own metabolism. No effect on its serum concentration or half-life, nor on those of isoniazid, were found after simultaneous oral administration of the two drugs. After treatment with rifampicin and p-aminosalicylic acid, the peak serum level of the former was delayed from 2 to 4 h, it was reduced from 8.0 to 3.8 µg/ml, and the mean area under the serum concentration curve throughout the entire 8 h study period was also lowered by about half. Individual patients did not attain therapeutically effective peak serum concentrations of rifampicin if also treated withp-aminosalicylic acid. The interaction observed between the two drugs is probably due to impaired gastrointestinal absorption of rifampicin, either by alteration of its physico-chemical properties or by a decrease in the gastric emptying rate combined with more rapid intestinal transit. The combination of these two drugs is unsuitable for the routine chemotherapy of tuberculosis.
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  • 14
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    European journal of clinical pharmacology 7 (1974), S. 249-252 
    ISSN: 1432-1041
    Keywords: Practolol ; renal failure ; uraemia ; beta-blockade ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of renal failure on the excretion of oral doses of practolol has been studied. The plasma half-life increased up to 6.6 times normal and the cumulative urinary excretion of the drug was reduced. There was a linear correlation between the overall elimination rate constant of practolol and inulin and creatinine clearances. A linear correlation was also found between the renal clearances of practolol and inulin. The dose of practolol required for maintenance therapy should be reduced in patients with impaired renal function.
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  • 15
    ISSN: 1432-0878
    Keywords: LRF ; Hypothalamic localization ; Rat ; Ependyma ; Glia ; Light and electron microscopic Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Light and electron microscopic autoradiographic analysis of the medial basal hypothalamus of rat brains incubated for 30 and 60 minutes in tritiated luteinizing releasing factor (3H-LRF) revealed selective uptake in the form of silver grains over specialized ependyma (tanycytes) and perivascular glial cells in the palisade-contact zone of the median eminence. The functional capacity of tanycytes and glia are discussed in light of these data.
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  • 16
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    Cell & tissue research 150 (1974), S. 493-496 
    ISSN: 1432-0878
    Keywords: Serotonin ; Neurotransmitter ; Myenteric plexus ; Rat ; Histofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Several recent studies suggested that serotonergic neuron-like elements are present in the guinea pig ileum. The present paper reports an extensive study of the digestive tract of the rat with the use of a histofluorescence technique. Administration of the serotonin precursor, tryptophan, associated with a monoamine oxidase inhibitor, did not allow histochemical demonstration of rapidly fading, yellow fluorescent, 6-hydroxydopamine-resistant neurons; conversely such neurons were readily detected in the brain. It is concluded that serotonergic neuron-like elements cannot be detected histochemically in the rat myenteric plexus area after chemical sympathectomy.
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  • 17
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    Cell & tissue research 151 (1974), S. 457-469 
    ISSN: 1432-0878
    Keywords: Juxtaglomerular apparatus ; Rat ; Adrenalectomy ; Renin and secretory granules ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Reaktion des juxtaglomerulären Apparates auf Adrenalektomie wurde untersucht. Im Stadium der Nebenniereninsuffizienz, sechs Tage nach der Operation, wurde quantitativ morphometrisch eine Abnahme der Volumendichte der Sekretgranula (von 32% auf 16%) festgestellt. Golgi-Apparat und Ergastoplasma proliferieren stark, wobei insbesondere die erweiterten Cisternen des Ergastoplasmas auffallen.
    Notes: Summary The response of the Juxtaglomerular apparatus to bilateral adrenalectomy was studied in rats. After the sixth postoperative day, symptoms of severe adrenal insufficiency had developed. In the Juxtaglomerular cells, the volume density of the secretory granules decreased from 32% to 16%. The Golgi apparatus and rough endoplasmic reticulum underwent considerable proliferation, the latter showing strikingly enlarged cisternae.
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  • 18
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    Cell & tissue research 151 (1974), S. 525-536 
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Rat ; Sex differences ; Gonadal hormones ; Karyometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Adrenal glands of adult female rats are heavier than the glands of corresponding male rats. Postpubertal orchiectomy increases the adrenal weight, an effect restored by testosterone replacement. Under the same conditions ovariectomy of 8 weeks duration does not change the adrenal weight while estradiol replacement enhances the relative adrenal weight. Karyometric studies have shown that nuclei in the female zona fasciculata cells are larger (app. 18%) than those of the male. Similar but only slight differences (2%) were observed in the zona reticularis. Orchiectomy results in enlargement of cell nuclei within all zones of the adrenal cortex; testosterone replacement has the opposite effect. Ovariectomy of 8 weeks duration slightly enhances the volume of nuclei of the zona glomerulosa cells, has no effect on the nuclei of the zona fasciculata and reduces the volume of nuclei in the zona reticularis. Estradiol replacement reduces the volume of nuclei of the zona glomerulosa cells but increases nuclear volume in the zona fasciculata and in the zona reticularis. Thus testosterone has an inhibitory effect on the adrenal cortex of the rat while the physiologic effect of estradiol on the morphology of this gland, particularly on the zona fasciculata cells is rather dubious. The author wishes to thank Mrs. B. Westerska and Miss K. Siejak for excellent technical assistance.
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  • 19
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    Cell & tissue research 151 (1974), S. 537-547 
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Rat ; Sex differences ; Gonadal hormone ; Stereologic studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Adult female rats have heavier adrenals than males. Orchiectomy increases the adrenal weight, an effect reversed by testosterone. Neither ovariectomy nor estradiol replacement has an effect on absolute adrenal weight. The stereologic analysis of the volume fractions of particular adrenocortical zones have shown that the volume fraction of the zona glomerulosa in females is smaller as compared with males. On the contrary, the volume fractions of the fasciculata and reticularis zones are higher in female than in male rats. In both sexes gonadectomy and gonadal hormone replacement has an effect on the volume fractions of particular adrenocortical zones, these changes being more pronounced due to orchiectomy or testosterone replacement. The adrenal cortex of all experimental groups contains a similar quantity of parenchymal cells. The cytoplasm volume of a single adrenocortical cell is higher in all zones of the female adrenals as compared with the male. Orchiectomy increases the volume of the cytoplasm in fasciculata and reticularis cells. This effect was reversed by testosterone. Neither ovariectomy nor estradiol replacement has an effect on the volume of the cytoplasm in the fasciculata and reticularis cells. These studies have shown that sex differences with regards to rat adrenal size and weight depend upon the “physiologic atrophy” of the male adrenal cortex, while neither ovariectomy (8 weeks after operation) nor estradiol replacement has a conspicuous effect on the morphologic changes of this gland.
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  • 20
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    Cell & tissue research 147 (1974), S. 259-269 
    ISSN: 1432-0878
    Keywords: Nerve endings ; Hair ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Palisade-shaped nerve endings of the small normal hairs of the rat snout were examined with the electron microscope (fixation by perfusion). The terminals are located inside the ‘glassy membrane’ in the area of the neck of the hair root. The 10–20 radially arranged terminal axons are in direct contact with the basement membrane of the epithelium of the external root sheath. The axons are surrounded on all sides by leaf-shaped processes of the Schwann cells. The surfaces of these cell processes are marked by numerous vesicle-like invaginations (approx. 1000 Å dia.). Transverse sections from several areas of the palisadeshaped nerve endings are compared with longitudinal sections. In the upper area ‘empty’ vesicles (approx. 500–600 Å in diameter) occur, along with electron-dense vesicles (approx. 800–1100 Å in diameter); in the middle area, the axons are distended and contain accumulations of mitochondria.
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  • 21
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    Cell & tissue research 147 (1974), S. 183-190 
    ISSN: 1432-0878
    Keywords: Kidney ; Rat ; Bowman's capsule ; Experimental hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The parietal layer of Bowman's capsule was examined in the rat in control animals and in animals made hypertensive by treatment with desoxycorticosterone acetatesaline and by clipping of the renal artery. At an early stage of elevation of blood pressure and, occasionally, prior to elevation of blood pressure, the epithelial cells of this layer showed basal cytoplasmic protrusion and reduplication accompanied by an increase in the thickness of the basement membrane. These changes preceded evidence of glomerular or renal arteriolar pathology. They presumably reflect either a response of this layer to increased blood pressure and modified glomerular function, or a direct effect of the factors that also induces blood pressure elevation. In either case, they imply a greater functional significance for the parietal layer than has usually been attributed to it.
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  • 22
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    Cell & tissue research 148 (1974), S. 57-67 
    ISSN: 1432-0878
    Keywords: Prostate ; Rat ; Cyproterone ; Alterations ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The dorsal lobe and the coagulating gland of the rat prostate were studied after administration of the anti-androgenic compound Cyp A for varying periods (7–20 days). There was a general involution of the organs with macroscopic atrophy and reduced amount of secretory material. Ultrastructurally the cells were pale, contained less organelles as compared with the controls, loss of cytoplasm and reduction both of cell height and width. The major changes also included reduction of the Golgi area, the rough endoplasmic reticulum and the number of free ribosomes. Within the dorsal lobe prominent nuclear changes were found, comprising different types of intranuclear inclusions of membranous configurations. The alterations observed in the present study are similar to the changes which were found in castrated animals and are consistent with atrophy. The results are discussed in relation to the available biochemical and autoradiographic data on the different lobes.
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  • 23
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    Cell & tissue research 150 (1974), S. 95-105 
    ISSN: 1432-0878
    Keywords: Mucosal mast cells ; Rat ; Compound 48/80 ; Degranulation, Release ; Light microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Mast cells in the tongue and lamina propria of the duodenal mucosa, representing two cell types with different morphological, histochemical and functional properties have been studied under the electron microscope. Both cell types were found to contain similar moderately electron dense and homogeneous granules surrounded by a tight membrane constituting the basic ultrastructural characteristics of mast cells. The mucosal mast cells, however, contained fewer granules per cell and the individual granules often exhibited considerable variation in size. In addition the mucosal mast cells, unlike those of the tongue, peritoneum and skin, had a smooth plasma membrane lacking microvilli and possessed irregularly shaped or lobulated nuclei. In the tongue mast cells, administration of Compound 48/80 caused the formation of vacuoles around the granules, expulsion of granules from the cells and disintegration of the granular matrix, but no changes that could be attributed to 48/80 could be found in the mucosal mast cells.
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  • 24
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    Cell & tissue research 154 (1974), S. 443-470 
    ISSN: 1432-0878
    Keywords: Oocytes and T-prospermatogonia ; Rat ; Quantitative analysis ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Bei der Ratte findet die sexuelle Differenzierung der Gonade zwischen dem 14. und 15. Tag post conceptionem (p.c.) statt. Während dieser Zeit teilen sich die Oogonien und deren Parallelpopulation—die M-prospermatogonien (multiplying prospermatogonia) oder I-Gonocyten—sehr häufig. Um den 17. Tag p.c. tritt die letzte Generation der Oogonien bzw. der M-prospermatogonien in die Mitose. Die Mitosen bilden häufig “synchronisierte Gruppen”. Die postmitotischen Kerne ihrer Tochterzellen—der Oocyten und der T 1 prospermatogonien (primary transitional prospermatogonia) oder II-Gonocyten—sind klein. Ihr Chromatin ist in Form gröberer Schollen der Kernmembran angelagert. Auf diese Weise kommt das typische “krustenförmige” Aussehen bzw. die Ähnlichkeit mit den Prophasen der Oogonien und M-prospermatogonien zustande. Die Oocyten durchlaufen zunächst die G1-phase (etwa 10 Std Dauer) und treten dann—am Ende des Präleptotänstadiums—in die S-phase. Dann passieren sie die verschiedenen Stadien der meiotischen Prophase und treten vom 3. Tag post partum (p.p.) ab in das Dictyotänstadium. Die T1-prospermatogonien hingegen befinden sich etwa 10 Tage lang in der G1-phase, ohne wesentliche morphologische Veränderungen aufzuweisen. Vom 4. Tag p.p. an durchlaufen sie die S-Phase. Die S-Phasen-Dauer (D-S) beider Zellarten beträgt 11.5 Std und wurde durch Doppelmarkierung mit 14C- und 3H-Thymidin bestimmt. Als am besten geeignete Termine für die Bestimmung der D-S erwiesen sich bei den Oocyten der 18. Tag p.c. und bei den T1-prospermatogonien der 5. Tag p.p. Zu diesen beiden Zeitpunkten war die Anzahl der in die S-phase ein-und austretenden Oocyten bzw. T1-prospermatogonien gleich, die Zellen in S-phase befanden sich im “steady state”. Das Kernvolumen der Oogonien und M-prospermatogonien ist etwa doppelt so groß wie das der postmitotischen Oocyten und T1-prospermatogonien. Bis zum 5. Tage p.p. nimmt das Kernvolumen der Oocyten und T1-prospermatogonien um etwa das Fünffache zu. Der Degenerationsindex der Oocyten liegt wesentlich höher als der der T1-prospermatogonien; er ist postnatal besonders hoch. Aus den T1-prospermatogonien gehen am 4. und 5. Tage p.p. durch Teilung die T 2-prospermatogonien (secondary transitional prospermatogonia) hervor. Die Kerne dieses Zelltyps sind etwas kleiner also die der T1-prospermatogonien. Die T2-prospermatogonien treten am 6. Tage p.p. in die Mitose; es entstehen die ersten A-spermatogonien.
    Notes: Summary In the rat (Wistar-WU) sexual differentiation of the gonads occurs between days 14 and 15 post conception (p.c.). At this time the oogonia and their parallel population — the M-prospermatogonia (I-gonocytes)—divide rapidly. On about day 17 p.c., the last generation of oogonia and M-prospermatogonia, frequently arranged in synchronized clusters, enters mitosis. The postmitotic nuclei of their daughter cells—oocytes and T 1-prospermatogonia (II-gonocytes)—are small; coarse flakes of chromatin are associated with the nuclear membrane causing the typical “crustlike” appearance and the similarity with the prophases of oogonia and M-prospermatogonia. After the oocytes have passed a G1-phase of approximately 10 hr, they enter the S-phase at the end of the preleptotene stage. Then they pass the different stages of the meiotic prophase until they enter the dictyate stage from 3 day post partum (p.p.) onwards. The T1-prospermatogonia, on the other hand, spend a long G1-phase of about 10 days without any conspicuous morphological change before entering the S-phase from day 4 p.p. onwards. The duration of the S-pbase (D-S) of both cell types—oocytes and T1-prospermatogonia—as determined by the double labeling method with 14C- and 3H-thymidine is found to be 11.5 hr. The most favourable time for determining the D-S was day 18 p.c. for the oocytes and day 5 p.p. for the T1-prospermatogonia. On these two days the balance was reached between the cells entering and leaving the S-phase. The nuclear volumes of the postmitotic oocytes and T1-prospermatogonia are approximately half the size of those of their precursors. Until day 5 p.p. the nuclear volumes of the oocytes and T1-prospermatogonia increase about fivefold. The degeneration index of the oocytes is considerably higher than that of the T1-prospermatogonia; postnatally it is especially high. T 2 prospermatogonia arise by mitosis of the T1-prospermatogonia on day 4 and 5 p.p. The nuclei of this cell type are smaller than those of T1-prospermatogonia. T2-prospermatogonia enter mitosis on day 6 p.p and give rise to A-spermatogonia.
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  • 25
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    Cell & tissue research 155 (1974), S. 231-243 
    ISSN: 1432-0878
    Keywords: Pinealocyte-resembling cells ; Habenular region ; Sympathetic nerve fibres ; Ontogenetic development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The cells of the pineal gland, the pineal stalk, and the lamina intercalaris contain 5-HT and are innervated by sympathetic nerve fibres. These peripheral nerve fibres continue rostrally from the lamina intercalaris and run into the central nervous tissue of stria medullaris and the habenular nuclei. Pharmacological treatment to increase the cellular 5-HT content revealed that the sympathetic fibres are in close relation to yellow fluorescent cells embedded in the brain tissue. These yellow fluorescent cells develop very late in the ontogenetic development (three weeks or more postnatally) and are preceded by ingrowth of sympathetic fibres into the brain tissue. The results support the hypothesis that the cells found in the habenular region are of pinealocyte rather than neuronal nature, but it is possible that they differ in certain aspects from the cells of the pineal gland proper.
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  • 26
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    Cell & tissue research 148 (1974), S. 203-211 
    ISSN: 1432-0878
    Keywords: Hypothalamus ; Rat ; Supraoptic nucleus ; Ultrastructure ; Somatic spines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Electron microscopic studies of ultrathin serial sections of the perikarya and adjacent neuropil of neurons of the supraoptic nucleus (SON) of the adult male rat revealed varying forms of two types of somatic spines. One type forms synapses with axons passing the cell, the other, without synapses, appears to serve as a buttress or clasp for adjacent neuronal and glial processes. The synapse-bearing spines lack the usual spine apparatus but contain the flocculent substance often seen in spines. The other spines do not exhibit either of these structures. These somatic spines were also seen in Golgi impregnated preparations but the types could not be distinguished. Certain axons synapse either on a somatic spine of the perikarya or penetrate the glial sheath of the neuron and synapse, usually repeatedly, on the soma in an en passant manner.
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  • 27
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    Cell & tissue research 148 (1974), S. 371-379 
    ISSN: 1432-0878
    Keywords: Pineal gland ; Rat ; Electric coupling areas ; Freeze-etching
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The pineal glands of Wistar rats were fixed in glutaraldehyde and prepared by the freeze-etching technique. With regard to the form and internal structure of pineal cells this technique has revealed nothing essentially new. Synaptic ribbons are very rarely found. A regular diagonal arrangement of membrane attached particles between the Schwann cell and the axon of an autonomic nerve terminal was observed. Three types of contact areas between pineal cells are described. In the first two types, which occur more frequently, the diameter of the area varied from 1000 to 2500 Å, with irregularly aggregated membrane associated particles. The third type, larger but less frequently found, has a surface area of 0.4 μm2 and much more regularly distributed membrane associated particles (ø 88 Å). These contact areas can be considered to be electric coupling areas between pineal cells.
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  • 28
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    Cell & tissue research 147 (1974), S. 285-292 
    ISSN: 1432-0878
    Keywords: Median eminence ; Rat ; Serotonin terminals ; 5,6- and 5,7-Dihydroxytryptamine ; Chemical degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Electron microscopical evidence for the existence of an important serotonergic input to the rat median eminence is presented. This evidence is based on the demonstration of degenerating nerve terminals in the external layer of the rat median eminence following the application of 5,6-dihydroxytryptamine or 5,7-dihydroxytryptamine, drugs known to exert more or less selective toxic effects on central serotonin neurons. The finding of a serotonergic innervation of the median eminence in mammals has important implications for 5-hydroxytryptamine as a modulator of synthesis and/or release of hypothalamic, hypophysiotropic hormones.
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  • 29
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    Cell & tissue research 149 (1974), S. 91-104 
    ISSN: 1432-0878
    Keywords: Anococcygeal muscle ; Smooth muscle ; Rat ; Innervation, adrenergic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rat anococcygeus muscle, which is known from previous functional and histochemical investigations to be a smooth muscle with a dense adrenergic innervation, was studied by electron microscopic methods. The muscle was found to be organized in small bundles of 2 to 8 muscle cells, which were interconnected by desmosome-like junctions and by gap junctions. Small Schwann cell-axon complexes with 1 to 5 axons appeared to represent the functional terminal nerve pathway. Such axon complexes were located at the periphery of the small smooth muscle bundles, they never penetrated into them. A ratio of approximately 6 small axon complexes per 100 muscle cells was found. After glutaraldehyde fixation axon varicosities contained mainly small empty vesicles. After treatment with 5-hydroxydopamine and permanganate fixation mainly small vesicles with a dense core were found. The neuromuscular distances ranged from 550 to 5000 Å, with a mean of about 2600 Å. True close neuromuscular contacts at a distance below 500 Å with a fusing of basal laminae were absent. The present observations provide a morphological base for the findings of previous electrophysiological and pharmacological studies on the anococcygeal muscle.
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    Cell & tissue research 149 (1974), S. 113-120 
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Rat ; Sex-hormones ; Ultramorphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Ultramorphometrisch wurde nach dem Verfahren von Rohr et al. (1971) die äußere Zona fasciculata von Sprague-Dawley-Ratten bei 5 Gruppen zu je 4 Tieren verglichen: Männchen, Weibchen im Diöstrus, Weibchen im Östrus, männliche und weibliche Kastraten (Kastration am 4. Lebenstag). Die Nebennierenrindenzellen der äu\eren Fasciculata sind bei Weibchen gegenüber denen normaler Männchen hypertroph: Weibchen im Diöstrus zeigen gegenüber Männchen größere Einzelzellen mit vermehrtem glattem endoplasmatischem Reticulum, erhöhten Einzel- und Gesamtvolumina der Mitochondrien sowie einem höheren Lipoidgehalt bei stärkerer Dispersion der Liposomen. Dieselben funktionsspezifischen Strukturen nehmen bei den Weibchen im Östrus noch weiter zu. Die Kastration der Weibchen am 4. Lebenstag führt zu einer Reduktion der funktionsspezifischen morphometrischen Parameter unter die Werte der Diöstrus-Tiere. Männliche Kastraten gleichen die Werte ihrer funktionsspezifischen Strukturen weitgehend denen der Weibchen im Diöstrus an. Nach Kastration am 4. Lebenstag zeigen weibliche Tiere somit etwas niedrigere morphonietrische Parameter in der äußeren Zona fasciculata als die männlichen Kastraten.
    Notes: Summary With the method of Rohr et al. (1971) the outer zona fasciculata of Sprague-Dawley-rats was compared ultramorphometrically in 5 groups of 4 animals each: males, females during diestrus, females during estrus, male and female castrates (castration on 4th day of life). Adrenal cortical cells of the outer fasciculata in females are hypertrophic in comparison with those of normal males: females during diestrus show in comparison with males larger individual cells with increased SER, increased volume of the individual mitochondrium and total volume of mitochondria as well as an increased lipoid content together with a more pronounced dispersion of liposomes. The same function-specific structures show a further increase in females during estrus. Castration of females on the 4th day of life leads to a reduction of the function-specific morphometric parameters below the values of the diestrus animals. Male castrates show adaption of the values of their function-specific structures towards those of females during diestrus. Following castration on the 4th day of life, female animals thus show somewhat lower morphometric parameters in the outer zona fasciculata than male castrates.
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    Cell & tissue research 149 (1974), S. 235-243 
    ISSN: 1432-0878
    Keywords: Adrenal zona glomerulosa ; Rat ; Normal ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This paper reports on an electron microscopic study of the adrenal zona glomerulosa in the normal rat, with special emphasis on the structural diversity of mitochondria in its parenchymatous cells. The mitochondria of cristae may be tubulo-vesicular, plate-like and/or straight tubular, any one mitochondrion containing one or more types of cristae. The mitochondrial features of the zona glomerulosa parenchymatous cells are attributed to the biochemical stages of aldosterone synthesis, taking place in different mitochondria of these cells.
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  • 32
    ISSN: 1432-0878
    Keywords: Hypothalamo-neurohypophysial system ; Rat ; Granule distribution ; Electron microscopy, morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Neurohypophyse und die neurosekretorischen hypothalamischen Kerngebiete von normalen männlichen und weiblichen Ratten, von trächtigen und durstenden Tieren wurden elektronenmikroskopisch und morphometrisch mit der Fragestellung untersucht, ob sich in den Häufigkeitsverteilungen der mittleren Granula-Durchmesser, bezogen auf die Anzahl der Axone, eine zweigipflige Verteilung ergibt. Bei Kontrolltieren zeigen die Perikarya des Nucleus supraopticus zahlreichere und größere Granula als die Zellen des Nucleus paraventricularis, wobei der Unterschied in den Durchmessern der Granula bei den weiblichen Tieren ausgeprägter ist als bei den männlichen. Beide Kontrollgruppen zeigen in der Neurohypophyse ein zweigipfliges Verteilungsmuster der Granula, wobei die beiden Gipfel bei den männlichen Kontrollen dichter beieinander liegen als bei den weiblichen. Bei den trächtigen Tieren weisen beide Kerngebiete Zeichen gesteigerter Aktivität auf und die Granula in den Zellen des Nucleus paraventricularis sind deutlich größer als bei Kontrolltieren. Zu Beginn der Tragzeit werden relativ große, wahrscheinlich vasopressinhaltige Granula in der Neurohypophyse gespeichert, während sich im letzten Drittel der Tragezeit die beiden Populationen dort nicht mehr unterscheiden lassen. Nach 48 Std. Wasserentzug erscheinen beide hypothalamischen Kerne aktiviert. Auffallend ist, daß die Granula im Nucleus supraopticus deutlich kleiner sind als bei Kontrolltieren. Entsprechend fehlen in der Neurohypophyse große Granula, während Axone mit kleinen Granula vermehrt sind. Nach zehntägiger Durstperiode lassen sich im Nucleus supraopticus, neben sehr typischen morphologischen Veränderungen, morphometrisch ebenfalls deutlich kleinere Granula nachweisen. Im Hypophysenhinterlappen dieser Versuchsgruppe sind die granulahaltigen Axone sehr stark vermindert, und in der Häufigkeitsverteilung fehlen die Granula mit großem Durchmesser während der dem Oxytocin zugeordnete Gipfel unverändert erscheint. In Verbindung mit den elektronenmikroskopischen Befunden lassen sich also aus den Verschiebungen der Verteilungsmuster zwischen den sechs Versuchsgruppen die Granula mit kleinerem Durchmesser oxytocinhaltigen Axonen zuordnen und Granula mit größerem Durchmesser zu den Endigungen, die Vasopressin enthalten. Die morphometrischen Befunde in den neurosekretorischen hypothalamischen Kerngebieten bestätigen diese Zuordnung. Die elektronenmikroskopischen und morphometrischen Befunde werden besonders im Hinblick auf die Hormonverschiebungen zwischen dem “reserve pool” und den “easily releasable pool” diskutiert.
    Notes: Summary A morphometric evaluation of electron micrographs has been carried out from neurosecretory terminals in the neurohypophysis and from the supraoptic and paraventricular nuclei in normal male and female rats as well as in pregnant and water deprived rats. The task of this investigation was to find out whether frequency distribution diagrams of the mean diameter of the neurosecretory granules, plotted versus the number of axons, reveal a grossly bimodal distribution. In normal rats the nerve cells of the nucleus supraopticus (S.O.N.) show more numerous and larger granules than the cells of the nucleus paraventricularis (P.V.N), this difference with respect to the diameter being more pronounced in female than in male animals. In the posterior pituitary lobes the neurosecretory granules exhibit a bimodal distribution, the second peak being situated more closely to the first one in male controls. In pregnant animals both nuclei appear to be activated, and the granules of P.V.N. are distinctly larger as compared to those of female control animals. In early pregnancy larger, i.e. presumably vasopressin-containing granules are stored in the neurohypophysis, while in the last phase before delivery oxytocin-containing neurons and vasopressin-containing ones cannot be differentiated any more. After 48 hrs of thirst both hypothalamic nuclei exhibit signs of increased activation, the diameters of the granules in the S.O.N. being distinctly smaller than in normals. In the neurohypophysis granules with large diameters are lacking, while axons with small granules are more frequent. In the S.O.N. of animals, water deprived for 10 days the diameters of the granules are smaller than normal and in the neurohypophysis the number of granule-containing fibres is strongly reduced. In the frequency distribution diagram granules with larger diameters are lacking whereas the peak, attributed to oxytocin, is not essentially altered. However, from the observed alteration on the distribution patterns of the six experimental groups and in connection with the electron microscopic results the granules with smaller diameters can be attributed to oxytocin-containing axons and the larger ones to vasopressin-containing terminals. Analogous morphometric data have been obtained from the neurosecretory nuclei as well. The electron-microscopic and morphometric observations are discussed with regard to hormone-shifts between the reserve pool and the easily-releasable pool.
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    Cell & tissue research 151 (1974), S. 471-480 
    ISSN: 1432-0878
    Keywords: Juxtaglomerular apparatus ; Rat ; Influence of deoxycorticosterone (DOC) ; Electron microscopy ; Morphometric analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die quantitativ-morphologische Analyse des juxtaglomerulären Apparates nach DOC-Behandlung zeigte, daß mit der Hemmung der Reninbildung eine Hypoplasie der epitheloiden Zellen des juxtaglomerulären Apparates einhergeht. Der Granulagehalt der juxtaglomerulären Zellen nahm ab; die Kern-Plasma-Relation änderte sich und die Leiomyofibrillen in den Epitheloidzellen nahmen zu. An den übrigen Anteilen des juxtaglomerulären Apparates, insbesondere der Macula densa, wurden keine morphologischen Veränderungen beobachtet. Die DOC-Behandlung führte darüber hinaus zu einer Bildung von Einschlüssen in den Podocyten, den Mesangiumzellen und den Zellen der Bowman-Membran. Die verschiedenen Möglichkeiten, über welche Faktoren die juxtaglomerulären Zellen nach DOC-Behandlung degranuliert werden, werden diskutiert. Das ultrastrukturelle Bild der Epitheloidzellen nach DOC-Behandlung entspricht deutlich einer gehemmten Sekretion, da das Ergastoplasma und der Golgi-Apparat ganz besonders stark zurückgebildet werden.
    Notes: Summary Quantitative morphological analysis of the Juxtaglomerular apparatus of rats treated with deoxycorticosterone (DOC) and salt revealed hypoplasia of the epithelioid cells as a concomitant of the inhibition of renin synthesis. The granular content of the Juxtaglomerular cells was significantly decreased, while the nucleus-to-cytoplasm ratio and the volume density of leiomyofilaments in the epithelioid cells increased. No morphological alterations were observed in the remaining constituents of the Juxtaglomerular apparatus, including the macula densa. DOC-treatment also induced the appearance of inclusions in the podocytes in the cells of the mesangium, and in the cells of Bowman's capsule. The possible mechanisms of degranulation of the Juxtaglomerular cells after treatment with DOC are discussed. The ultrastructural appearance of the epithelioid cells after treatment with DOC corresponds to an inhibition of secretion, since the rough endoplasmic reticulum and the Golgi apparatus undergo marked regressive changes.
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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
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    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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    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
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    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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  • 36
    ISSN: 1573-8744
    Keywords: digoxin ; pharmacokinetics ; two-compartment model ; three-compartment model ; radioimmunoassay
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    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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    Journal of pharmacokinetics and pharmacodynamics 2 (1974), S. 347-364 
    ISSN: 1573-8744
    Keywords: metoprolol ; β-receptor antagonist ; pharmacokinetics ; disposition
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of 3H-metoprolol, a new selective β 1-receptor antagonist, have been studied in healthy volunteers by following the plasma concentrations and the urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. The compound was rapidly and completely absorbed after oral administration, and about 40% of the dose reached the systemic circulation. The estimated half-life of the absorption process was 10 min. Metoprolol was extensively distributed to extravascular tissues, with the half-life of the distribution phase close to 12 min. About 95% of the dose was excreted in the urine within 72 hr, mainly in metabolized form. The elimination halflife of the compound was close to 3 hr as was also the half-life of the total metabolites after oral administration. After intravenous administration, the elimination half-life of the metabolites was raised to 5 hr, indicating that the route of administra tion might influence the metabolic pathways of the parent compound.
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    Bulletin of experimental biology and medicine 78 (1974), S. 1150-1152 
    ISSN: 1573-8221
    Keywords: methindione ; pharmacokinetics
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    Topics: Biology , Medicine
    Notes: Abstract The pharmacokinetics of the new anticonvulsant, methindione, carbon-labeled in the carbonyl and N-methyl groups, was studied in experiments on rats. Methindione is quickly absorbed from the gastro-intestinal tract and passes easily through tissue barriers. The highest concentration of methindione in the brain is observed 15–30 min after administration. The metabolism of methindione and its elimination from the tissues take place rapidly. In most tissues only 6–23% of its maximal concentration still remains after administration of the drug. Metabolites of methindione, labeled in the carbonyl group, are excreted mainly through the kidneys, but metabolites labeled in the N-methyl group are excreted chiefly through the lungs.
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    Bulletin of experimental biology and medicine 78 (1974), S. 1379-1381 
    ISSN: 1573-8221
    Keywords: fluorouracil ; pharmacokinetics ; radiometry
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    Topics: Biology , Medicine
    Notes: Abstract The dynamics of the concentration of radioactivity in the blood serum, organs, and urine was investigated after intravenous injection of 5-fluorouracil-2-C14 into rats. The preparation is rapidly absorbed from the blood into the tissues in which it accumulates rapidly in high concentrations and it is excreted quickly from the body. The half-elimination period of 5-fluorouracil in the blood is 15 min. It is excreted chiefly by extrarenal routes.
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    Calcified tissue international 13 (1973), S. 113-129 
    ISSN: 1432-0827
    Keywords: Kinetics ; Growth ; Epiphyses ; Hypophysectomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La largeur de la métaphyse tibiale, la zone indifférenciée, la zone sériée et les cellules en dégénerescence ont été observées chez des rats Sprague-Dawley normaux et hypophysectomisés. La production cellulaire de la métaphyse est déterminée sur la base de la croissance osseuse longitudinale déterminée par l'oxytétracycline et la taille des cellules en dégénérescence. La diminution de la croissance osseuse longitudinale, en fonction de l'augmentation de l'âge et après hypophysectomie, est due partiellement, à la diminution de production cellulaire et partiellement à une décroissance de la taille des cellules en dégénérescence dans la métaphyse. L'influence de la production cellulaire et de l'activité mitotique prédomine.
    Abstract: Zusammenfassung Die Breite der proximalen Wachstumsplatte der Tibia, deren undifferenzierter und säulenförmiger Zone und die Größe der nahe bei der Metaphyse auftretenden degenerativen Zellen wurden in normalen und hypophysektomierten Sprague-Dawley-Ratten bestimmt. Die Zellproduktion in der Wachstumsplatte wurde aus dem longitudinalen Knochenwachstum berechnet, welches mittels Oxytetracyclin und der Größe der degenerativen Zellen bestimmt wurde. Es wurde festgestellt, daß die Abnahme des longitudinalen Knochenwachstums bei zunehmendem Alter und nach Hypophysektomie zum Teil einem Rückgang in der Zellproduktion, zum Teil einer Verminderung der Größe der degenerativen Zellen in der Wachstumsplatte zuzuschreiben ist. Der Einfluß der Zellproduktion, und somit der mitotischen Aktivität, herrscht vor.
    Notes: Abstract The width of the proximal growth plate of the tibia, its undifferentiated and columnar zone and the size of the degenerative cell close to the metaphysis, were determined in normal and hypophysectomized Sprague-Dawley rats. The cell production in the growth plate was calculated from the longitudinal bone growth determined with oxytetracycline and the degenerative cell size. It was found that the decrease in longitudinal bone growth with increasing age and after hypophysectomy, is due partly to a decrease in cell production, and partly to a decrease in degenerative cell size in the growth plate. The influence of cell production and thus the mitotic activity predominates.
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  • 41
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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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  • 42
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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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  • 43
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    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
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    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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  • 44
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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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  • 45
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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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  • 46
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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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  • 47
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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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  • 48
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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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  • 49
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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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  • 50
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    Cell & tissue research 139 (1973), S. 101-148 
    ISSN: 1432-0878
    Keywords: Infundibulum ; Rat ; Neuro-glial synapses ; Neuro-Vascular contacts ; Corticotropin-Releasing Factor ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung 1. Die Gefäßfortsätze von ependymalen und subependymalen Zellen bilden in der subependymalen Zone und in der Zona interna des Ratteninfundibulum mit Nervenfasern kompakte neuro-gliöse Faserbündel, die sich in der Zona externa aufzweigen. 2. In allen Zonen des Infundibulum kommen zwischen den Nervenfasern und den Gefäßfortsätzen zahlreiche neuro-gliöse Synapsen vor. In den Gefäßfortsätzen fällt die hohe Zahl an Mikrotubuli sowie die zahlreichen, vielgestaltigen Einschlüsse auf. 3. In der subependymalen Zone sind die Interzellularspalten an bestimmten Stellen außerordentlich weit. Sie haben eine kanalartige Beschaffenheit und enthalten feine Bündel von Nervenfasern. 4. Von den lateralen Anteilen des Infundibulum her erreichen Dendriten von Ganglienzellen des Nucleus infundibularis die Mitte des Infundibulum. In dieser Region sind axodendritische Synapsen anzutreffen. 5. Morphometrische Analysen der Nervenfaserendigungen der Zona externa von Normaltieren zeigen, daß die prozentuale Verteilung der nach Granulagröße differenzierten Nervenfaserklassen für Mitte und Seite der Zona externa etwa gleich ist. Zwischen der Größe der Elementargranula und der Anschnittfläche der zugehörigen Nervenfasern besteht eine direkte Beziehung. 6. Die Nervenfaserendigungen erreichen die Basalmembran des perikapillären Raumes fast ausschließlich im Bereich von gefäßwärts gerichteten Vorwölbungen der Zona externa. Das Ausmaß, in dem Nervenfasern im Vergleich zu den Gefäßfortsätzen von Ependymund Gliazellen den perivaskulären Raum erreichen, ist medial weitaus größer als lateral. 7. Bei bilateral adrenalektomierten Ratten nimmt in bestimmten, vorwiegend lateral gelegenen Nervenfasern die Zahl und Größe der Elementargranula in Abhängigkeit von der Überlebensdauer zu. Dies dürfte auf eine verstärkte Synthese und Speicherung von Corticotropin-Releasing Factor in diesen Nervenfasern zurückzuführen sein. Gegenüber dem Normalbefund ist die neurohämale Kontaktfläche erheblich vergrößert. Der perivaskuläre Raum enthält zerfallene Nervenfaserteile, die durch Bindegewebszellen phagocytiert werden. Diese Veränderungen dürften durch eine unter Versuchsbedingungen verstärkte Wachstumstendenz der Nervenfasern in Richtung auf die Blutgefäße und durch eine Abschnürung der Nerven-faserendigungen ausgelöst werden.
    Notes: Summary 1. In the subependymal and internal zones of the rat median eminence nerve fibres and vascular processes of ependymal and subependymal cells form neuro-glial bundles. They branch in the external zone. 2. In all these three zones of the infundibulum numerous neuro-glial synapses are found between nerve fibres and vascular processes of glial cells. The vascular processes contain a high number of microtubules as well as polymorphous granular inclusions. 3. In certain regions of the subependymal layer the intercellular spaces are enlarged. They form channel-like spaces containing small bundles of delicate nerve fibres. 4. Nerve cells of the infundibular nucleus located in the lateral parts of the infundibulum send dendrites to the medial parts of the infundibulum. In this area axo-dendritic synapses are found. 5. For morphometric analysis, the nerve fibres of the external zone were classified according to the diameter of their granules. It is shown that in the different regions of the external zone the distribution of the various types of nerve fibre is similar. Moreover it can be seen that a direct correlation exists between the size of the sectional plane of a given nerve fibre and the size of the granules it comprises. 6. Nerve fibre endings abutting on the basement membrane of the pericapillary space are mostly found in bulb-like protrusions of the external zone. The extent to which nerve fibres reach the perivascular space—as compared with the vascular processes of ependymal and glial cells—is higher in the medial than in the lateral parts of the infundibulum. 7. In bilaterally adrenalectomized rats the number and diameter of elementary granules increases in nerve fibres located laterally. This increase is directly related to the survival time and may be due to an enhanced synthesis and storage of Corticotropin-Releasing Factor in these nerve fibres. Compared with the findings in untreated animals the neurohemal contact area is significantly enlarged. The perivascular space contains degenerating nerve fibres which are undergoing phagocytosis by connective tissue cells. It is assumed that these alterations are due to the increased growth of nerve fibres towards the vessels of the “Mantelplexus”, and that, following adrenalectomy, this excessive growth leads to a pinching off of nerve fibres.
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    Cell & tissue research 138 (1973), S. 261-272 
    ISSN: 1432-0878
    Keywords: Extrarenal blood vessels ; Rat ; Adrenergic nerves ; Fluorescence microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The adrenergic innervation of the extrarenal blood vessels of the rat left kidney was investigated by fluorescence histochemistry and by electron microscopy. The trunk of the renal artery proximal to the aorta is elastic and appears to be very sparsely innervated. In contrast, near the kidney the renal artery—which divides into 3 to 4 large branches of the muscular type possesses a dense adrenergic innervation. The adrenergic terminal axons are situated in the adventitia close to the external elastic lamella, but only rarely in close contact with smooth muscle cells. In most instances several terminal axons are grouped and enclosed by a Schwann cell, single axons being rare. All terminal axons are able to take up and to store 5-hydroxydopamine which strongly suggests that they are adrenergic. The innervation of the renal vein is more sparse than that of the muscular arteries but somewhat denser than that of the elastic artery. In addition, close to the origin of the renal artery the presence of “small intensively fluorescent” (SIF) cells as well as of some adrenergic ganglion cells is noted. The latter are situated in the adrenergic nonterminal axon bundles, which run parallel to the blood vessels. It is concluded that the uneven adrenergic innervation along the artery as well as individual variations in the branching of the artery are the main causes of the unusually high individual variations of the NA content of this organ such as used in pharmacological experiments.
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  • 52
    ISSN: 1432-0878
    Keywords: Adenohypophysis ; Rat ; Gonadotrophic cells ; Cycle, influence of testosterone ; Light microscopy
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    Notes: Summary 4-day cyclic adult female Wistar rats were injected subcutaneously with testosterone propionate on diestrus 1 at 16:00 and on diestrus 2 at 10:00 respectively. Non-injected females served as controls. Autopsy was performed on diestrus 2 at 23:00, and on proestrus at 14:00 and 17:00 respectively. The blue Alcian-PAS staining was used to evidence FSH (β) and LH (γ) pituitary cells. In control animals and in diestrus 2 injected females only a small number of FSH cells could be detected on diestrus 2 at 23:00. This number increased markedly on proestrus at 14:00 and decreased on proestrus at 17:00. A similar evolution was observed in diestrus 1 testosterone injected females, but the number of FSH cells appeared higher at any stage of autopsy in these females than in diestrus 2 injected females and in control rats. In control females, numerous LH cells were observed on diestrus 2 at 23:00. The number of these cells was diminished on proestrus at 14:00 and still more at 17:00. On the contrary few LH cells were detected in testosterone injected females on the evening of diestrus 2. An increase of these cells occurred on proestrus at 14:00, followed at 17:00 by only a weak diminution as established by comparison with control animals. An inhibition of FSH release and a suppression of the proestrus surge of LH were therefore supposed to cause, on one hand, the slowing up of follicular growth observed in diestrus 1 injected females and, on the other hand, the blockage of ovulation noted in both diestrus 1 and diestrus 2 treated animals.
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    Cell & tissue research 143 (1973), S. 107-116 
    ISSN: 1432-0878
    Keywords: Neurohypophysis ; Rat ; Pituicytes ; Organotypic culture ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary Neural lobes of adult rats have been explanted and organ-cultured for 5–10 days. While perivascular cells and neurosecretory fibers undergo a progressive degeneration, scattered pituicyte-like cells are observed mostly associated with each other in number of two or three cells for group. Cultured pituicytes are quite similar to in vivo pituicytes except for some particular features as the shape of the nucleus and the number of dense bodies. Furthermore they share with the in vivo pituicytes the phagocytic capacity which appears even increased as far as neurosecretory fibers are concerned. Finally, degenerating pituicytes and free lipid droplets are observed in the intercellular spaces: the significance of these facts is discussed and tentatively interpreted. The organotypic culture of the neural lobe seems to represent an experimental model useful to obtain a relatively pure population of pituicytes.
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    Cell & tissue research 143 (1973), S. 505-515 
    ISSN: 1432-0878
    Keywords: Endoplasmic reticulum ; Paracervical ganglion (Rat) ; Neurosecretion ; Electron microscopy ; Rat
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    Notes: Summary Two new types of structure of the cytoplasm of an autonomic neuron were described: (1) Inclusions of the rough ergastoplasmic reticulum, which were named “ergastosomes”, contain finely granular material with moderately electron opaque staining with both glutaraldehyde-OsO4 and KMnO4 fixations. A short comment was made on the nature of the contents of the ergastosomes. (2) Tubular formations of endoplasmic reticulum were found in the axons and/or dendrites of the paracervical ganglion.
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  • 55
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    Cell & tissue research 146 (1973), S. 453-461 
    ISSN: 1432-0878
    Keywords: Hypophysis ; Primordium ; Rat ; Organ culture ; Electron microscopy
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    Notes: Summary To see whether adenohypophysial tissue has the capacity of self-differentiation, Rathke's pouch together with part of the neurohypophysial primordium was isolated from 12-(Group A), 14- (Group B) and 15-day-old (Group C) rat fetuses and cultivated for 9, 6 and 5 days, respectively. Electron microscopic examination of these explants showed many adenohypophysial cells containing electron dense granules, indicative of cytodifferentiation in all groups. Three cell types were distinguishable on the basis of the size of their granules. Variable amounts of neurohypophysial tissue were seen in some explants of Groups B and C, but not A. This “pars nervosa” contained pituicytes with lipid-like inclusions in their cytoplasm but no neurosecretory axons. The adenohypophysial cells abutting on the pars nervosa were arranged rather regularly like cells of the pars intermedia which contained a few granules of about 200 mμ diameter. From these data it is concluded that in rats granule formation in the adenohypophysial primordial cells starts in the absence of hypothalamic neurosecretory substances. It is uncertain from this study whether these cells actually contain hypophysial hormones.
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    Cell & tissue research 144 (1973), S. 453-466 
    ISSN: 1432-0878
    Keywords: Lacrimal gland ; Rat ; Duct system ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary The duct system of the rat exorbital lacrimal gland consists of intercalated ducts, interlobular ducts and excretory ducts. The morphological changes from one type of duct to the next are gradual. At the light microscopical level this consists of a change from a bilaminar epithelium in the intercalated ducts to an epithelium, consisting of approximately three layers — which may be pseudostratified — in the excretory ducts. The basal layer of the intercalated ducts consists of myoepithelial cells, whereas the inner epithelial cells may have both a secretory and an electrolyte transporting function. The interlobular duct epithelium contains many cells with deep infoldings of the basolateral plasma membranes and associated mitochondria, suggesting a similar function to the striated duct epithelium in salivary glands. Numerous basal cells in this epithelium have tentatively been interpreted as unusual myoepithelial cells. Nerve terminals have been observed in the ductal epithelium.
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    Cell & tissue research 136 (1973), S. 111-120 
    ISSN: 1432-0878
    Keywords: Median eminence ; Rat ; Granular vesicles ; Ultrastructure ; Quantitative evaluation
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    Notes: Summary In order to characterize different sub-zones in the palisade zone of the rat median eminence, quantitative ultrastructural parameters were applied to brains fixed in aldehyde-osmium tetroxide. The palisade zone has been subdivided in 4 successive sub-zones. Increasing numbers of granular vesicles (GV), especially those smaller than 110 nm, are observed from dorsal to ventral sub-zones. There also are more GV per unit area of nervous tissue in the perivascular than in the more dorsal sub-zones. The individual nerve profiles exhibit a larger size in the perivascular layer than in the more dorsal areas, whereas the number and size of nerve profiles devoid of vesicles diminish from dorsal to ventral. As a consequence more GV occur in the perivascular nerve profiles. In the GV containing nerve profiles the concentration of GV is, however, constant in the different sub-zones. A fluctuating size of the preterminal and terminal parts of the nerve fibres is suggested.
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    Cell & tissue research 136 (1973), S. 177-182 
    ISSN: 1432-0878
    Keywords: Rat ; Epididymis ; Effect of vasectomy ; Spermatozoa ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Epididymal biopsies from rats that had undergone unilateral or bilateral vasectomies from one to eight months previously were compared with biopsies from their contralateral side or from normal controls to ascertain what ultrastructural changes had occurred. After vasectomy, spermatozoa appeared to dissolve in the lumen of the caput epididymidis and to be absorbed by the principal cells. About 5 weeks after vasectomy, numerous lamellar accumulations became apparent in the supernuclear region. Their resemblance to lysosomes or residual bodies was confirmed by an acid phosphatase reaction. After 10 weeks, similar lamellar and polymorphic accumulations on the contralateral side of animals with unilateral vasectomies indicated that resorption had also increased on the unligated side.
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    Cell & tissue research 138 (1973), S. 223-237 
    ISSN: 1432-0878
    Keywords: Aorta, endothelium ; Rat ; Transport of serum lipoproteins ; Radioautography ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The transport of 125I-labeled serum lipoproteins through the aortic endothelium was studied by radioautography. Rat aorta and heart was perfused in vitro with a medium containing human very low density (VLDL), low density (LDL), high density lipoprotein (HDL), delipidated HDL apolipoprotein or rat HDL. In all lipoproteins more than 95% of the radioactivity was TCA precipitable and lipid radioactivity was from 2–4% in HDL, 4–6% in LDL, 7–15% in VLDL. After 18–60 min of perfusion and wash with unlabeled medium, most of the aortic radioactivity was TCA precipitable and the percent of lipid counts was similar to that in the original lipoprotein. Following perfusion with VLDL, LDL, or HDL the radioautographic reaction was seen over the endothelium, the subendothelial space and the inner media, and was separated by an unlabeled zone from the reaction present over the adventitia. Uniform labeling of the entire wall was found after perfusion with HDL apolipoprotein. The presence of silver grains over endothelial cells in regions rich in plasmalemmal vesicles suggested that these organelles participate in the transport of the labeled lipoprotein, as was shown for lactoperoxidase (Stein and Stein, 1972). The present data indicate that cholesterol may enter the aortic wall as a constituent of lipoprotein particles. Since an HDL particle carries less than 1/20 of the cholesterol present in a LDL particle, it seems that the lower susceptibility of the female to atheromatosis might be related to the higher ratio of HDL to LDL particles in the female serum.
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    Cell & tissue research 137 (1973), S. 141-143 
    ISSN: 1432-0878
    Keywords: Juxtaglomerular cells ; Rat ; Granulation index ; Diurnal rhythm ; Statistical evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Das Granulations-Index der juxtaglomerulären epitheloiden Zellen der Rattenniere unterliegt tagesrhythmischen Schwankungen, wobei die berechneten Werte in den Nachtstunden significant höher sind als in den Tagesstunden.
    Notes: Summary Marked diurnal changes occur in the granulation index of the juxtaglomerular cells in the rat kidney. According to the results the night values are significantly higher than those obtained in daytime.
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    Cell & tissue research 140 (1973), S. 309-314 
    ISSN: 1432-0878
    Keywords: Pituitary Gland ; Rat ; Somatotropin ; Cellular Response ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The response of somatotrophs to large doses of purified bovine growth hormone was examined in uninephrectomized rats drinking 1% sodium chloride in an attempt to prolong the action of the hormone. Growth hormone produced a triphasic response in the ultrastructure of somatotrophs. Uninephrectomy and salt alone induced no changes in somatotrophs as compared to unoperated animals consuming tap water. In the first phase (3 days) the cross sectional area of the cell increased, the size of the largest granule per cell as well as the number of granules per cell increased significantly. All these parameters then reached control level after 7 days of injections during a second phase. Suppression of somatotrophs by exogenous growth hormone was evident by 16 days (third phase) when the area of the cell, the size of the largest secretory granule as well as the number of granules per cell all decreased significantly. Somatotrophs apparently did not react to suppression by a lysosomal mechanism inasmuch as no increase in the number of lysosome-derived structures was seen even at 16 days.
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    Cell & tissue research 143 (1973), S. 143-147 
    ISSN: 1432-0878
    Keywords: Rat ; Suprachiasmatic nucleus ; Blinding ; Retinohypothalamic connections ; Karyometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Radioaktiv markierte Aminosäuren werden bei Säugetieren nach intraokulärer Injektion nicht nur zu den primären optischen Kerngebieten, sondern auch in den Nucleus suprachiasmaticus des Hypothalamus transportiert (Moore und Lenn, 1972; Hendrickson, Wagoner und Cowan, 1972; Moore, 1973). Dieser Befund macht eine direkte Verknüpfung zwischen der Netzhaut und dem sekretorisch aktiven Nucleus suprachiasmaticus wahrscheinlich, obwohl mit Silbertechniken eine solche Verbindung nicht sicher nachgewiesen werden konnte. Karyometrische Studien am Nucleus suprachiasmaticus männlicher Wistar-Ratten zeigen 6 Tage nach beidseitiger Blendung eine signifikante Abnahme der Zellkerndurchmesser. Dieses Ergebnis spricht für eine Aktivitätsänderung der Neurone im Nucleus suprachiasmaticus geblendeter Ratten.
    Notes: Summary Intraocular injection of labeled amino acids results, in different mammals, in an accumulation of radioactive material not only in the primary optic centers but also within the hypothalamic suprachiasmatic nucleus (Moore et al., 1972; Hendrickson et al., 1972; Moore, 1973). This finding argues in favour of a direct connection between the retina and the secretory suprachiasmatic nucleus although silver techniques do not show such a pathway. In male Wistar rats the nuclear diameter of the suprachiasmatic neurons decreases significantly 6 days after bilateral experimental ablation of the retina. These results indicate an alteration in activity of the suprachiasmatic neurons in blinded rats.
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    Cell & tissue research 143 (1973), S. 535-547 
    ISSN: 1432-0878
    Keywords: Adenohypophysis ; Rat ; Mitoses, topographic distribution ; Influence of fixation ; Light microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Les mitoses de l'adénohypophyse du rat mâle ont été examinées comparativement après fixation par perfusion et après fixation par immersion. Après fixation par perfusion la répartition topographique des mitoses dans le parenchyme est homogène, et l'index mitotique est de 1,85 pour 1 000 cellules. Après fixation par immersion, la densité des mitoses décroit de la périphérie vers le centre, et l'index mitotique n'est que de 0,80 mitoses pour 1 000 cellules. La lenteur de pénétration du fixateur pendant l'immersion est tenue pour principal responsable des différences observées. Elle entraîne une modification de l'aspect des mitoses, telle que plus de la moitié d'entre elles ne sont pas identifiables et échappent aux comptages.
    Notes: Summary The mitoses of the adenohypophysis in male rats have been observed comparatively after fixation by perfusion and fixation by immersion. After fixation by perfusion, the topographic distribution of mitoses throughout the parenchyma is homogenous and the mitotic index is 1.85 for 1 000 cells. After fixation by immersion, the density of the mitoses is decreasing from the periphery towards the center and the mitotic index is only 0.80 for 1 000 cells. The slow penetration of the fixative during fixation by immersion is considered to be the main cause in the differences observed. This slow action causes a modification in the aspect of the mitoses, and more than fifty percent of them cannot be identified and escape to the counts.
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    Cell & tissue research 144 (1973), S. 167-178 
    ISSN: 1432-0878
    Keywords: Prostate ; Rat ; Castration ; Alterations ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ventral, lateral and dorsal lobes of the rat prostate were studied 2, 3, 5, 7 and 21 days after castration. The major changes were a general reduction of the Golgi area and the RER. The cells became pale and contained less organelles compared with the normals. One of the most conspicuous changes were enormous autophagic vacuoles which were present already after 2 days, seemed to reach a numerical peak 3 days after castration and were seldom encountered after 7 days. Increased number of dense bodies were found within the same period. Lipid droplets were observed in the basal cytoplasm of the epithelial cells, especially in the ventral lobe. The basal cells showed the same involution as in the ordinary epithelium. In addition, macrophages were relatively numerous, and between the epithelial cells also lymphocytes were found. The results are discussed in relation to biochemical data on the different lobes.
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    Cell & tissue research 144 (1973), S. 179-189 
    ISSN: 1432-0878
    Keywords: Seminal vesicles ; Coagulating Gland ; Rat ; Castration ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The seminal vesicles and the coagulating gland of the rat were studied 2, 3, 5, 7 and 21 days after castration. The major changes within the seminal vesicles were primarily formation of whorls of the rough endoplasmic reticulum (RER), followed by a general atrophy with a numerical reduction of the RER-profiles, and with general simplification of the cytoplasm due to loss of the organelles. It was a gradually reduction of secretion granules, diminution of the Golgi apparatus, formation of pigment bodies and autophagic vacuoles. Lipid droplets were observed in the basal cytoplasm of the epithelial cells. In the coagulating gland, similar changes occurred within the Golgi area and the lysosome complex. On the other hand, cisternae of the basal endoplasmic reticulum tended to persist in many cells. The similarity in response strongly suggests that the pathogenetic mechanisms are similar in both organs, i.e. atrophy due to deprivation of the androgenic stimulus. The deprivation of androgen gave rise to an inflammatory-like process with infiltration of lymphocytes and macrophages. The increased number of macrophages may indicate that they contribute in some way to the involution of the prostate by removing the material in the autophagic vacuoles.
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    Cell & tissue research 140 (1973), S. 473-479 
    ISSN: 1432-0878
    Keywords: Testicular feminization ; Rat ; Leydig cells ; Sterility ; Androgens, Steroids ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The interstitial cells of the pseudohermaphrodite rat testis are both hypertrophic and hyperplastic. The cytoplasm is characterized by smooth endoplasmic reticulum which is abundant and variable in form. Mitochondria are numerous and large with tubular cristae and occasional inclusions. Structural features of the Leydig cells indicate potential for increased steroid synthesis. The presence of large numbers of mast cells in the intertubular area is confirmed. Small seminiferous tubules lack advanced germinal elements. Additional connective tissue and myoepithelial layers produce a thickening of the limiting membrane. Some myoepithelial cells are atypical with an electron translucent cytoplasm and nuclei with dense peripheral chromatin. No spermatogenic cells beyond the cap phase of the spermatid are observed. The cytoplasm of Sertoli cells contains large lipid droplets and degenerating germ cells.
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    Cell & tissue research 146 (1973), S. 463-471 
    ISSN: 1432-0878
    Keywords: Neurosecretory granule ; Pars nervosa ; Rat ; Morphometry
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    Topics: Biology , Medicine
    Notes: Summary The distribution of the diameters of the neurosecretory granules in the rat pars nervosa (measured from electron micrographs taken at 40 000 × ) was compared among axons by nonparametric statistical methods and the axons were classified into five groups with median granule diameters of 143, 155, 167, 180 and 193 nm. We suggested that these five axon types carried different secretory substances contained in the pars nervosa.
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    Cell & tissue research 137 (1973), S. 361-374 
    ISSN: 1432-0878
    Keywords: Neurohypophysis ; Rat ; Saline-treatment ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary Neural lobes from rats which had been allowed to drink hypertonic saline for five days were examined electron microscopically and by bioassay of oxytocin levels. The profound changes in the ultrastructure were examined and the reversal of these changes in morphology was followed until the hormone levels returned to normal. The recovery of the gland as measured by the two parameters of structure and hormone content indicated that the morphological recovery apparently preceded the hormone level recovery, a factor which might be explained by continued release of hormone during the period of recovery.
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    Cell & tissue research 136 (1973), S. 511-520 
    ISSN: 1432-0878
    Keywords: Muscle spindle ; Sensory ending ; Rat ; Development ; Electron microscopy
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    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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    Cell & tissue research 137 (1973), S. 271-280 
    ISSN: 1432-0878
    Keywords: Dental enamel ; Rat ; Ultrastructure ; Crystallography
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    Topics: Biology , Medicine
    Notes: Summary Thin sections of rat incisor enamel were studied with the electron microscope. Fringe patterns having repeat periods in the range 3.1–8.2 Å were seen in individual enamel crystals. These images were interpreted as representing the resolution of corresponding planes in the hydroxyapatite crystal lattice. The lattice spacings and interplanar angles were identified by comparing the observations with available data derived from X-ray diffraction analysis.
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  • 71
    ISSN: 1432-0878
    Keywords: Pars tuberalis ; Rat ; Development ; Secretion ; Ultrastructure
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    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 146 (1973), S. 207-221 
    ISSN: 1432-0878
    Keywords: Substantia nigra ; Rat ; Six bouton types ; Strio-nigral projection ; Bouton degeneration ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Summary The normal ultrastructure of rat substantia nigra was investigated. Special attention was paid to the different types of boutons, and the mode of termination of the striatonigral connection was examined. Two different types of nigra neurons with deep nuclear membrane indentations were observed. The synaptic organization of rat substantia nigra is very complex. Six types of boutons, with many characteristics, could be differentiated: pleomorphicvesicle boutons (40%), elongated-vesicle boutons (10%), small-round-vesicle boutons (10%), large-round-vesicle boutons (20%), “clear-terminal” (15%) and dense-core-vesicle boutons (about 5%). Vesicle-containing dendrites were observed entering dendro-dendritic synapses. One to four days after large unilateral striatal lesions were made, a great number of degenerating boutons were seen in the ipsilateral substantia nigra, while the contra-lateral substantia nigra was entirely free of degeneration. The newly defined pleomorphic-vesicle boutons were found almost exclusively in the process of degeneration. The neuronal origin of the other bouton types is discussed.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 51-68 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; cell kinetics ; mathematical model ; cell cycle specific drugs
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Predictive models have been developed to simulate cancer cell populations under treatment with cytotoxic drugs, with both direct-acting and cell cycle specific drugs being considered. Models of cell growth kinetics have been combined with simple pharmacokinetic models to complete the cell-drug interaction system. The models depend on knowing the distribution of generation time in the cell population, the cell-drug interaction, and the local concentration of the drug at the effective site. All of the quantities can be obtained, in principle, from separate experiments and combined to form a model describing several aspects of the cell-drug response system.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 497-520 
    ISSN: 1573-8744
    Keywords: tissue distribution ; plasma protein binding ; tissue protein binding ; fat/water partition coefficient ; volumes of distribution ; corticosterone ; pharmacokinetics
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The concentration of a drug at its site of action will be affected by the ability of the drug to distribute to and pass through various membranes and tissues. Mechanisms of drug distribution are summarized in this paper and include the differences between intracellular and extracellular pH,active transport systems for drugs, distribution of drugs between fat and water in adipose tissues, the reversible binding of drugs to phospholipids and to various macromolecules including proteins, nucleic acid, and melanin. These mechanisms usually tend to decrease the concentration of unbound drugs at their sites of action, but usually not to the extent one would predict on the basis of in vitrobinding studies. The effects of drug distribution in altering the biological half-lives of drugs in the body are discussed as well as the interrelationship between the kinetic volumes of distribution for drugs and blood flow rates through the organs that eliminate these drugs. These concepts are illustrated for corticosterone levels following intravenous bolus injections and infusions into rats.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 341-361 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacokinetic models ; bioavailability ; clinical metabolic profile ; chronic dosing regimens
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The present status of pharmacokinetics is reviewed. Pharmacokinetic models and the basic concepts involved in applying models to blood, urine, bile, and tissue levels of drugs and metabolites are discussed. An outline of methods for pharmacokinetic analyses is proposed. Special emphasis is given to the determination of bioavailability of a drug from various dosage forms. Uses of pharmaco-kinetics in determining sites of drug action and in determining a clinical metabolic profile are suggested. The perturbations of magnitudes of pharmacokinetic parameters among individuals challenged with the drug can be used as a diagnostic tool in evaluating the state of dynamic processes, the presence of metabolic diseases and genetic abnormalities, and the failure of physiological functions. The use of pharmacokinetics and the prediction of chronic dosing regimens are reviewed. Typical curves depicting predicted blood levels on repetitive dosing are presented.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 521-540 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; polygenically controlled disease states ; pharmacokinetic twin studies ; pharmacokinetic heritability ; ethanol ; antipyrine ; phenylbutazone ; bishydroxycoumarin.
    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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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 137-163 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; nonlinear regression ; drug distribution ; compartmental models ; computer program ; BASIC ; time sharing ; spectinomycin ; naloxone
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    Topics: Chemistry and Pharmacology
    Notes: Abstract COMPT, a computer program for optimizing the solution of integral compartmental models of drug distribution by nonlinear regression analysis, is written in extended BASIC for use in time-sharing computer systems. It is based on Hartley's modification of the Gauss-Newton gradient method. The characteristics and features of the program are indicated, and the program source listing is presented. This version of COMPT is designed to solve the two-compartment open model of intravenous drug administration. Examples of the results of the operational program are presented. The program is modifiable to permit analytical solutions for other types of systems described by nonlinear equations.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 175-200 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; cancer chemotherapy ; pharmacodynamics ; cell kinetics ; vincristine ; vinblastine ; arabinosylcytosine ; cyclophosphamide
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacodynamic model is proposed and equations are developed for the quantitative analysis of dose-time-cell-survival curves produced by the administration of cell-cycle-specific chemo-therapeutic agents. The essential feature of the model is an irreversible, bimolecular mechanism of drug-receptor interaction which serves as the interface between the pharmacokinetics of the drug and the cell-cycle-cell-proliferation kinetics of the normal and neoplastic cells. A preliminary cell system which allows adequate characterization of the experimental data is a two-compartment model where cells are assumed to exist in their proliferative and nonproliferative phases. The chemotherapeutic model was used to analyze dose-time-cell-survival curves found in the literature for the effects of vincristine, vinblastine, arabinosylcytosine, and cyclophosphamide on lymphoma and hematopoietic cells in the mouse femur. Similarity in the values of the “cell-kill” constants for these drugs on the two cell types indicates that, in the cell systems studied, the proliferative state of the cells is the primary in vivodeterminant of selective chemotherapy.
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    Keywords: absorption ; amphetamine ; bioavailability ; elimination ; pharmacokinetics ; phentermine ; resin-bound drugs
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma levels of amphetamine and phentermine have been measured in man in a crossover study of the pharmacokinetics of these agents following oral administration of resin-bound and soluble salt formulations. The one-compartment open model with first-order drug absorption was fitted to the data from each subject by nonlinear regression methods and provided an excellent fit. Relative bioavailability of the two salts did not differ for either drug. In both cases the rate constant for absorption was significantly lower and less variable for the resinated compound.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 295-305 
    ISSN: 1573-8744
    Keywords: diazoxide ; pharmacokinetics ; stable-isotope dilution ; GC-mass fragmentography ; solubility ; excretion
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A specific, sensitive, and accurate assay for diazoxide in human plasma and urine samples was developed utilizing stable-isotope dilution-GC-mass fragmentography. 3-Trideuterodiazoxide (d 3-diazoxide) served as internal standard, and diazoxide was N-methylated with diazomethane prior to GC. Plasma elimination half-lives of diazoxide ranged within 20–53 hr in four severely hypertensive patients, which did not correlate with endogenous plasma creatinine levels. A rapid infusion over 10–15 sec of an antihypertensive dose presumably resulted in a very transient precipitation of diazoxide due to its limited solubility of approximately 380 Μg/ml plasma. Urinary excretion accounted for 4–6% of the dose within 24 hr after administration in the four patients studied and totalled 19% and 22% in two patients. Renal clearance of diazoxide was below 1 ml/min on the first day following administration and increased to 2–3 ml/min on consecutive days. It was concluded that renal excretion of diazoxide is self-limited by antihypertensive doses in severely hypertensive patients. The major route of elimination in these patients may be due to metabolism.
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    Journal of pharmacokinetics and pharmacodynamics 1 (1973), S. 89-98 
    ISSN: 1573-8744
    Keywords: clindamycin ; clindamycin-2-palmitate ; clindamycin-2-hexadecylcarbonate ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology
    Notes: Abstract To determine the bioavailability of clindamycin from the microbiologically inactive clindamycin-2-palmitate and clindamycin-2-hexadecylcarbonate in man, a three-way crossover study was conducted with oral administration of the two esters and clindamycin hydrochloride. In each case, serum clindamycin bioactivity concentrations were fitted to a one-compartment open model with an initial lag time. Analysis of variance of measured quantities (serum concentrations and urinary excretion) and of derived pharmacokinetic parameters showed that for every comparison except maximum serum concentrations clindamycin-2-palmitate was not significantly different (at p=0.05) from clindamycin hydrochloride. Clindamycin-2-hexadecylcarbonate gave significantly different values from those for the hydrochloride in all cases except the rate constant and half-life for elimination from the serum. The palmitate was the superior ester and was bioequivalent to the hydrochloride in man.
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    Calcified tissue international 10 (1972), S. 238-251 
    ISSN: 1432-0827
    Keywords: Growth ; Bone ; Rat ; Tetracycline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La vitesse de croissance normale en longueur de la métaphyse proximale du tibia est déterminée chez le rat Sprague-Dawley entre les âges de 20 et 100 jours, en utilisant la méthode à la tétracycline. Le taux de croissance ne varie que légèrement dans les groupes d'âges différents. Il est plus élevé chez les animaux jeunes et décroit considérablement en fonction de l'augmentation de l'âge. Les rats mâles présentent une croissance plus élevée que les femelles. Cette étude a pour but de mettre au point une méthode permettant de déterminer les facteurs expérimentaux, liés à la croissance en longueur du rat.
    Abstract: Zusammenfassung Die normale Längenwachstums-Geschwindigkeit der proximalen Wachstumsplatte der Tibia wurde bei Sprague-Dawley-Ratten in einem Alter zwischen 20 und 100 Tagen mittels der Tetracyclinmethode gemessen. Die Wachstumsgeschwindigkeit variierte nur wenig innerhalb der einzelnen Altersgruppen. Die Geschwindigkeit war bei jungen Tieren am höchsten und nahm mit zunehmendem Alter beträchtlich ab. Männliche Ratten wuchsen schneller als weibliche. Diese Arbeit dient als Grundlage, um die experimentelle Beeinflussung des Längenwachstums der Ratte abschätzen zu können.
    Notes: Abstract The rate of normal growth in length from the proximal growth plate of the tibia in the Sprague-Dawley rat was measured between 20 and 100 days of age using the tetracycline method. The growth rate varied only slightly within different age groups. The rate was highest in young animals and decreased considerably with increasing age. Male rats grew faster than female. This study is intended to provide a base for an evaluation of experimental influence on the growth in length of the rat.
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    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Keywords: alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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    European journal of clinical pharmacology 5 (1972), S. 58-61 
    ISSN: 1432-1041
    Keywords: Pralidoxime chloride ; pharmacokinetics ; anti-cholinesterase poisoning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose of 1.0 g (10.0–14.0 mg/kg body weight) of pralidoxime mixed with various cholinolytics was given by i.m. injection to 29 healthy male subjects. A concentration of pralidoxime in blood of 4 µg/ml was reached after 5 to 10 min with all the mixtures and was maintained for about 1 to 2 h. The calculated half lives of pralidoxime in three groups of subjects were 62.2, 60.0 and 61.8 min., respectively. — The urinary excretions of pralidoxime during the first 4 h after the injections averaged 75.0, 79.6 and 69.6 per cent, respectively, of the total amount given. — The results are compared with published information about similar oximes.
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    European journal of clinical pharmacology 4 (1972), S. 233-240 
    ISSN: 1432-1041
    Keywords: Sulphamethoxazole ; trimethoprim ; pharmacokinetics ; uraemia ; sulphonamides
    Source: Springer Online Journal Archives 1860-2000
    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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  • 86
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    European journal of clinical pharmacology 4 (1972), S. 191-195 
    ISSN: 1432-1041
    Keywords: Amobarbital ; pentobarbital ; barbiturates ; gas chromatography ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    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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  • 87
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    European journal of clinical pharmacology 4 (1972), S. 137-141 
    ISSN: 1432-1041
    Keywords: Fentanyl ; pharmacokinetics ; neuroleptanalgesia ; analogue computer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and urinary excretion of3H-fentanyl were studied in 5 human subjects after intravenous injection of this drug. After an initial rapid decline, the plasma level of fentanyl decreased slowly and approximately exponentially. The plasma concentration of metabolites remained almost steady from 1–3 h after injection. More than 60% of the administered radioactivity was excreted through the kidneys within 4 days. Only a small proportion of it was unchanged fentanyl. The rates of fall of plasma concentration and of urinary excretion were slower in man than in rabbits. — The time courses of plasma concentrations and of urinary excretion were simulated on an analogue computer. The results support the assumption that the different time courses of concentrations in man and rabbits are caused by slower metabolism in man. It seems likely that redistribution plays a dominant part in the short duration of action of fentanyl in man.
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    European journal of clinical pharmacology 4 (1972), S. 150-157 
    ISSN: 1432-1041
    Keywords: Antibiotics ; pharmacokinetics ; microbiological assay ; drug control ; neonatal septicaemia
    Source: Springer Online Journal Archives 1860-2000
    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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  • 89
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    Cell & tissue research 126 (1972), S. 261-277 
    ISSN: 1432-0878
    Keywords: Adrenal medulla ; Rat ; Cell types ; Secretion ; Influence of fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Das Nebennierenmark der Ratte wurde nach Anwendung verschiedener Fixationsmethoden untersucht. Nach Immersionsfixation mit Glutaraldehyd oder Osmiumtetroxyd finden sich in der Nebenniere sog. Mischzellen, helle Zellen, syncytiale oder plasmodiale Zellen, die von den Untersuchern als Artefaktbildungen angesehen werden. In allen Proben nach Perfusionsfixation wurden solche Artefaktbildungen niemals beobachtet. Bei Immersionsfixation wurde eine enge Beziehung zwischen Sekretgranula und Cytoplasmamembran beobachtet, was bei Perfusionsfixation selten der Fall war. Die heutigen Theorien über den Sekretionsmechanismus bei Nebennierenmarkzellen werden aufgrund der vorgelegten Ergebnisse diskutiert. Die Arbeit zeigt die wesentlichen Vorteile der Anwendung der Perfusionsfixation für die Untersuchung der Nebenniere.
    Notes: Summary The adrenal medulla of the rat was studied utilizing various methods of fixation. In adrenal medulla specimens after immersion fixation either with glutaraldehyde or osmium tetroxide, elements such as mixed, clear, syncytial, or plasmodial cells, believed to be of artifactual origin, are observed in all of this material examined. These elements are absent in the specimens prepared by perfusion fixation. In specimens prepared by immersion fixation, secretory granules are found in close proximity to the plasma membrane; this localization is infrequent after perfusion fixation. Current theories of the mechanism of secretion of adrenal medullary hormones are discussed on the basis of our results. This investigation demonstrates the advantage and necessity of perfusion fixation in the study of the adrenal medulla.
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    Cell & tissue research 126 (1972), S. 466-482 
    ISSN: 1432-0878
    Keywords: Macrophages ; Microtubules ; Enamel organ ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the enamel organ of rat incisors macrophages are present in the zone of matrix formation, the transitional zone, the enamel maturation and pigmentation zone. The macrophages accumulate adjacent to redifferentiating amelocytes in the transitional zone. The macrophages phagocytize fragments of disintegrating amelocytes. In addition to the well known complement of organelles the macrophages present an elaborated microtubular system, scattered, thick filaments, a cortical feltwork of thin filaments, and spherical nuclear bodies. The microtubules emanate from “attached” and free pericentriolar satellites and radiate aster-like towards the cell surface or into pseudopods or curve along the nuclear surface for long distances, often related to nuclear constrictions. It is suggested that the microtubular system plays a prominent role in directional movement of the macrophages. The cortical filaments, if contractile, may create the cytoplasmic flow necessary for the cell motility.
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  • 91
    ISSN: 1432-0878
    Keywords: Olfactory tubercle ; Rat ; Degeneration ; Synapse
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    Topics: Biology , Medicine
    Notes: Summary The olfactory tubercle of the rat was studied by electron microscopy both in the normal and after ipsilateral olfactory bulb ablation at survival times of from 14 hours to seven days. Particular emphasis was placed on synaptic structures and their changes following the lesion. Normal synapses are similar to those described in previous studies and presynaptic profiles are of at least three types. Types-A and -B contain round vesicles and form asymmetrical contacts and type-C profiles contain flattened vesicles and form symmetrical contacts. There appear to be two major types of degenerative changes. The electron-lucent type predominates at early survival times and is seen first at 14 hours. These profiles show an early reduction in numbers of vesicles with mitochondrial swelling followed by shrinkage of the profile. These profiles become increasingly electron-dense at later survival times. The second major type of degenerating profile is initially electron-dense. The earliest changes in these profiles are an increased axoplasmic density and increased microtubular density and clumping without apparent loss of vesicles. These profiles also become progressively more electron-dense at longer survival times. The observations are discussed in relation to previous reports.
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  • 92
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    Cell & tissue research 127 (1972), S. 201-208 
    ISSN: 1432-0878
    Keywords: Spermatogenesis ; Rat ; Mitosis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The pattern of intercellular cytoplasmic bridges between rat spermatogonia and between spermatocytes is illustrated from electron microscopy of serial sections. Clones, or syncytia, containing as many as 22 connected spermatogonia and as many as 74 connected spermatocytes were observed. The absence of closed rings of cells agrees with the observation that intercellular bridges are the result of incomplete cell division, rather than cell fusion. The bridges thus are a record of spermatogonial divisions within a clone. In early spermatogonial generations there is a predominantly linear arrangement. The groups of spermatocytes have more side branches. From the presence of synaptonemal complexes it is concluded that the connected spermatocytes of a given clone are in about the same developmental stage. The pattern of intercellular bridges indicates, however, that not all nuclei in a clone undergo mitosis in the same cycle. The connected cells of a clone are therefore not all of the same generation. From unconnected bridges it is assumed that new clones originate from single cells or groups of spermatogonia which separate from an existing clone.
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  • 93
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    Cell & tissue research 130 (1972), S. 171-179 
    ISSN: 1432-0878
    Keywords: Tubuli seminiferi ; Rat ; Structure ; Contractility ; Organ culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Isolated pieces of seminiferous tubules of adult rats were grown in organ culture for up to 8 weeks in Petri dishes on the surface of nutrient agar. The medium consisted of newborn calf serum, Eagle's minimum essential medium, glutamate and antibiotics. This method allowed observation of the contractions of the seminiferous tubules in the culture. Contractility, light and electron microscopic structure and histochemically demonstrable activities of alkaline phosphatase and ATPase of the tubule walls were studied at 1-week intervals. The contractility and alkaline phosphatase activity were maintained in the tubule wall for 3 weeks, and the activity of ATPase was maintained for 5 weeks. The thin filaments of the myoid cells, which are responsible for the contractility, were seen with the electron microscope in tubules cultured for 5 weeks. The organ culture method described in the present paper seems to be valuable for studies concerning the functioning of the myoid cells of the seminiferous tubules and the possibility that this is regulated by hormones.
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    Cell & tissue research 131 (1972), S. 99-107 
    ISSN: 1432-0878
    Keywords: Median eminence ; Rat ; Exocytosis ; Micro-pinocytosis ; Releasing factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Exocytosis has been demonstrated by electron microscopy in the external zone of the median eminence of the rat. Exocytotic profiles have been observed in nerve fibres characterized by the presence of granular vesicles with median diameters of 90–103 nm and agranular vesicles of about 50 nm. In addition to the small agranular vesicles, coated vesicles of the same size have been found in many nerve fibres, suggesting that at least part of the agranular vesicles in the median eminence originate by micro-pinocytosis. The nature of the fibres showing exocytosis is discussed. Attention is drawn to the possibility of identifying types of fibres in the median eminence by the occurrence of exocytosis.
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    Cell & tissue research 132 (1972), S. 553-562 
    ISSN: 1432-0878
    Keywords: Basement membrane ; Brain ventricles ; Rat ; Subependymal labyrinths ; Light- and electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Mit der Perjodsäure-Bisulfit-Aldehydthionin-Färbung (Specht) lassen sich am ganzen Ventrikelsystem des Rattengehirns sub- und interependymale Strukturen lichtmikroskopisch nachweisen, die elektronenmikroskopisch als Basalmembranlabyrinthe (BML) identifiziert werden können. Verschiedene Formen dieser BML lassen sich unterscheiden. Sie stehen in Verbindung mit subependymalen Kapillaren. Die Verteilung der BML wird in Ventrikelkarten dokumentiert.
    Notes: Summary Sub- und interependymal structures, being demonstrable by a period-acid-bisulfit-aldehydthionine-method (Specht), occur in the whole ventricular system by light microscopy. They can be identified electron microscopically as basement membrane labyrinths (BML). Different shapes of these BML can be distinguished. They are in communication with the basement membrane of subependymal capillaries. The distribution of BML is documented in “ventricular maps”.
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    Cell & tissue research 134 (1972), S. 205-225 
    ISSN: 1432-0878
    Keywords: Diabetes insipidus ; Rat ; Hypothalamo-neurohypophysial system ; Synthesis of hormones ; Light- and Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The general ultrastructural features of the hypothalamo-neurohypophysial system in rats with hereditary hypothalamic diabetes insipidus (DI-rats, Brattleboro strain) are described. There is no decisively distinguishing difference between the neurons of the supraoptic and paraventricular nuclei. The neurons of both nuclei show signs of active protein synthesis. The perikarya of the neurons are markedly hypertrophic, the nuclei are large and the nucleoli prominent. In the cytoplasm there are numerous ribosomes, abundant rough-surfaced endoplasmic reticulum and extensive Golgi complexes. However, very few neurosecretory granules are to be seen. The axons of the hypothalamo-neurohypophysial tract are likewise enlarged and the paucity of neurosecretory granules is a striking feature also in the area of the tract. The majority of nerve endings in the posterior pituitary of DI-rats are devoid of neurosecretory granules. Microvesicles are abundant in the nerve endings and there are findings which suggest that microvesicles are involved either in endoor exocytosis. The signs of active protein synthesis and the concomitant paucity of neurosecretory granules are interpreted to imply transportation of the secretory proteins in an extragranular phase. The possible mode of release of the secretory proteins from the nerve endings and the role of microvesicles therein are discussed.
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    Cell & tissue research 132 (1972), S. 25-34 
    ISSN: 1432-0878
    Keywords: Neurohypophysis ; Rat ; Perivascular cells ; Neurosecretion ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The purpose of this study is to investigate the ultrastructural features of perivascular cells as found in the neural lobe of the hypophysis. In particular, an inquiry was made into the nature of the relationship of such cells to neurosecretory fibers and endings. The latter, in fact, are often invaginated within the perivascular cells and enveloped by their processes; furthermore, they often reveal a certain number of empty granules as well as characteristics of degenerative nature. In the course of this study the localization of the perivascular cells has been investigated as well as that of their processes within the extensive interlobular network typical of the hypophysial neural lobe of rodents. Based on the data gathered, the hypothesis is put forward that the perivascular cells play an important role in the turnover of neurosecretory endings, both under physiological and experimental conditions, contributing thereby to the release of post-hypophysial hormones.
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    Cell & tissue research 125 (1972), S. 277-288 
    ISSN: 1432-0878
    Keywords: Neurohypophysis ; Rat ; Exocytosis ; Freeze-etching ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Neural lobes of rats subjected to severe acute haemorrhage under sodium pentobarbitone anaesthesia were examined electron microscopically and the ultrastructure compared with that in anaesthetised and unanaesthetised controls. Changes in the localisation and numerical distribution of elementary granules and small vesicles in the neurohypophysial nerve endings of bled rats were consistent with the occurrence of exocytosis. The occurrence of “exocytotic profiles” was observed more frequently in freeze-etched tissue samples as compared with the material fixed for conventional electron microscopy. The ratio of small vesicles: elementary granules was shown to be significantly increased (P〈0.005) in the nerve endings of neural lobes from bled rats. Equally, the numbers of exocytotic profiles related to 1000 μm2 of neurohypophysial tissue area were significantly greater (P〈0.005) in bled rats.
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    Cell & tissue research 125 (1972), S. 289-294 
    ISSN: 1432-0878
    Keywords: Accessory optic system ; Rat ; Blood vessels ; Extracellular space ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two types of capillaries were found in the medial terminal nucleus of the rat accessory optic system. Type one capillaries are surrounded by glial processes and lack a perivascular space, whereas the type two capillaries and arterioles show a distinct extracellular perivascular space often filled with collagen fibrils. An internal as well as an external basal lamina lines these spaces. No fenestration of the endothelium was observed.
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    Cell & tissue research 125 (1972), S. 415-431 
    ISSN: 1432-0878
    Keywords: Synapses ; Rat ; Cerebral cortex ; Glutaraldehyde/E-PTA ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Synaptic junctions in intact rat cerebral cortex have been examined following glutaraldehyde fixation and phosphotungstic acid (PTA) staining. In the presynaptic ending the network has a hexagonal arrangement, while the dense projections are regularly placed along the presynaptic membrane. Cleft densities occupy the intracleft region. The postsynaptic thickening extends uninterrupted along the length of the junction. Qualitatively, the majority of junctions fall into the ‘discontinuous-continuous’ category, in which the internal coat of the presynaptic membrane together with its associated dense projections is discontinuous along the length of the junction, whereas the postsynaptic thickening is continuous. By contrast, a small number of junctions are ‘continuous-continuous’. In an attempt to analyze the junctions quantitatively, nine indices were measured. Histograms of the size distributions of seven of these appear to be bimodal, and from this it is concluded that two junction populations may be distinguishable on quantitative grounds. It is also shown that the distance separating dense projections at the presynaptic membrane is of the order of 10–15 nm. This surprisingly low value has consequences for current ideas on the relationship between synaptic vesicles and dense projections, and these are discussed at length.
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