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  • Articles  (119)
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  • Histochemistry  (71)
  • pharmacokinetics  (48)
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  • 1970-1974  (119)
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  • Articles  (119)
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  • Springer  (119)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 16 (1974), S. 169-182 
    ISSN: 1432-0827
    Keywords: Histochemistry ; Alkaline phosphatases ; Calcification ; Bone ; Teeth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Activity of alkaline phosphatases in unfixed cold microtome setions from the lower first molar area of newborn mice was recorded by histochemical methods. A substrate specificity test included the following phosphate compounds: ATP, CTP, GTP, UTP, ADP, AMP, GP, PPi, MDP and naphthol AS-TR phosphate. Intense staining was obtained in osteoblasts, stratum intermedium of the enamel organ and odontoblasts with all the substrates, except PPi and MDP. Staining of skeletal muscle fibres was obtained only with triphosphates as substrates. Addition of-SH groups decreased the hydrolysis of triphosphate compounds in cells involved in mineralization while the hydrolysis of monophosphate was inhibited. In contrast triphosphatase activity in striated muscle was enhanced when-SH compounds were added. Demineralization with EDTA diminished the cytoplasmic staining but induced a nuclear staining in hard tissue forming cells when triphosphates were used as substrates. No cytoplasmic and only slight nuclear staining was seen with GP or AMP as substrates. The triphosphate hydrolyzing capacity of tongue muscle fibres was, however, increased after the decalcification treatment. Addition of Mg2+ ions to the incubation media distinctly lowered the hydrolysis of triphosphates in the investigated tissues whereas the hydrolysis of ADP, AMP, GP and naphthol AS-TR phosphate remained unchanged. In view of the findings the triphosphatase activities at alkaline pH of muscle fibres and of cells related to hard tissue formation are considered to be due to activity of separate enzymes. The orthophosphate liberating enzyme activities at alkaline pH in osteoblasts, stratum intermedium and odontoblasts may be expressions of the catalytic functions of one common enzyme. Furthermore, the results indicate that CaATP might be the substrate used by the alkaline ATPase in mineralizing areas.
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  • 2
    ISSN: 1432-0827
    Keywords: Cartilage ; Mineralization ; Histochemistry ; Matrix vesicles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les expériences portent sur la minéralisation de la plaque épiphysaire tibiale du rat de souche Long-Evans, étudiée après traitement à la cortisone, propylthiouracile ou après jeûn prolongé. Dans des conditions normales, le calcium et le phosphate augmentent au niveau de la matrice extracellulaire, alors que les mucopolysaccharides sulfonés diminuent. Par contre, les vésicules de la matrice au niveau desquels se forment les cristaux d'hydroxyapatite, augmentent. Dans les rats ayant subi un traitement à la propylthiouracile, les cristaux d'hydroxyapatite sont très apparents. Ceci est du à une augmentation du dépôt en calcium, et à une diminution des granules des mitochondries qui contiennent probablement du calcium et du phosphate. En outre, une augmentation du nombre des vésicules de la matrice est visible ainsi qu'une décroissance de la quantité des mucopolysaccharides sulfonés. Dans les rats traités à la cortisone, les cristaux d'hydroxyapatite sont présents, mais dans une quantité moindre que dans les rats ayant subi l'effet du propylthiouracile. Le dépôt en calcium est légèrement réduit; les granules des mitochondries sont plus nombreuses que dans les groupes précédents, le nombre des vesicules de la matrice est plus faible, et les mucopolysaccharides sulfonés sont plus apparents que dans les rats traités à la propylthiouracile. Dans les rats ayant subi l'effet du jeûn, les cristaux d'hydroxyapatite sont fortement réduits ou entièrement absents. Ceci est du à une réduction de dépôt du calcium, une augmentation du nombre des granules des mitochondries (ce qui semble indiquer que les phénomènes de transport vers la matrice extracellulaire sont ralentis), alors que les vésicules de la matrice sont présentes dans des quantités réduites. Les mucopolysaccharides sont plus apparents que dans les animaux traités à la cortisone ou à la propylthiouracile.
    Abstract: Zusammenfassung Die Untersuchung beruht auf einem Vergleich der Mineralisation in der hypertrophischen Zone in der Epiphysealplatte von Long Evans Ratten die mit Kortison, Propylthiourazil oder einfachem Fasten behandelt wurden. Unter Normalbedingungen lassen sich in der extrazellulären Matrix der Calcifikationszone die folgenden Veränderungen beobachten: der Gehalt an Calcium und Phosphat nimmt zu, derjenige an Mukopolysacchariden nimmt ab, während die Matrixvesiclen, in denen sich die Bildung des Hydroxylapatits vollzieht, zunehmen. In Ratten die mit Propylthiourazil behandelt wurden, treten die Hydroxylapatitskristalle besonders hervor. Dies hängt mit einer Zunahme der Calciumablagerung zusamen sowie einer Abnahme der Mitochondriengranulation (in denen vermutlich Calcium und Phosphat enthalten sind). Ferner hängt damit zusammen eine numerische Zunahme der Matrixvesiceln sowie ein starke Abnahme des Gehalts an sulfonierten Mucopolysacchariden. In den mit Kortison behandelten Ratten sind Hydroxylapatikristalle nachweisbar, wenn auch weniger zahlreich als in den mit Propylthiourazil behandelten. Dem entspricht auch eine leicht reduzierte Calciumablagerung sowie eine Mitochondrialgranulation die derjenigen der anderen Ratten überlegen ist; Matrixvesiceln sind weniger zahlreich und sulfonierte Mucopolysaccharide sind deutlicher nachweisbar als in den Tieren, die Propylthiourazil erhielten. Fasten führt zu einem auffallenden Verlust an Hydroxylapatitkristallen. Diese können sogar nicht mehr zu erkennen sein. Dies hängt mit verminderter Calciumablagerung zusammen sowie einer Zunahme der Mitochondrialgranulation. Dies ist vermutlich Ausdruck einer Transportverzögerung zur extrazellularen Matrix. Nach Fasten ist auch die Anzahl der Matrixvesiceln auffallend herabgesetzt, und der Gehalt an sulfonierten Mucopolysacchariden ist größer als in den mit Kortison bzw. Propylthiourazil behandelten Tieren.
    Notes: Abstract Comparison of mineralization in the hypertrophic zone of the tibial epiphyseal plate in immature rats was carried out after treatment with cortisone, propylthiouracil, or after fasting. Under normal conditions, in the extracellular matrix at the calcification front, calcium and phosphate increased, sulfated mucopolysaccharides decreased, and matrix vesicles, which serve as the locus for the formation of hydroxyapatite crystals, increased. In propylthiouracil-treated rats, hydroxyapatite crystals were prominent, related to an increase in calcium deposition, a decrease of mitochondrial granules (thought to contain calcium and phosphate), an increase in the number of matrix vesicles, and to a marked decrease in the amount of sulfated mucopolysaccharide. In cortisone-treated rats, hydroxyapatite crystals were present but they were not as numerous as in the propylthiouracil-treated rats. Correspondingly, calcium deposition was slightly reduced, mitochondrial granules were more numerous than in the previous groups of rats, matrix vesicles were less numerous, and sulfated mucopolysaccharide were more prominent than in the propylthiouracil-treated rats. In fasted rats, hydroxyapatite crystals were markedly reduced or absent, and related to a decrease in calcium deposition, an increase in the number of mitochondrial granules (suggesting a delay in transport to the extracellular matrix). Matrix vesicles were markedly reduced in number, and sulfated mucopolysaccharide much more prominent than in either the cortisone or the propylthiouracil-treated rats.
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  • 3
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    European journal of clinical pharmacology 7 (1974), S. 407-414 
    ISSN: 1432-1041
    Keywords: Diuretic ; indapamide ; human pharmacology ; toxicology ; pharmacokinetics ; TLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na+, K+ and Cl− and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca2+, Mg2+ and PO 4 3− rose in spite of a fall in urinary concentrations of these ions. The Ca2+ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.
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  • 4
    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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  • 5
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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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  • 6
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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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  • 7
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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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  • 8
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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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  • 9
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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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  • 10
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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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  • 11
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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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  • 12
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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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  • 13
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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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  • 14
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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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  • 15
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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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  • 16
    ISSN: 1432-0878
    Keywords: Autonomic nerves ; Pteropus giganteus (Chiroptera) ; Wing vessels ; Denervation ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The neuro-vascular complex was investigated at the brachial and digital levels in the wings of the flying-fox, Pteropus giganteus (Megachiroptera). Fluorescence histochemistry of the adrenergic transmitter (formaldehyde method) revealed a dense plexus of adrenergic nerve terminals in the adventitia of the main arteries. No fibres penetrated into the muscular media. The pulsating veins received a less well-developed fluorescent plexus which, however, was distributed throughout the muscular wall. Cholinesterase activity was observed in plexuses having the same density and distribution as the catecholamine-storing fibres. The identity of these cholinesterase-containing nerves has been discussed. Transection of the brachial nerve resulted in a pronounced, though not complete, denervation of the vessels examined at the metacarpal level 14 hrs to 6 weeks postoperatively. The results of the denervation experiments are probably related to the finding that the autonomic vascular nerves enter the wing not only via the brachial nerve trunk but also together with the blood vessels.
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  • 17
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    Cell & tissue research 150 (1974), S. 497-503 
    ISSN: 1432-0878
    Keywords: Testis ; Human foetus ; Leydig cells ; Steroid hormone synthesis ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Human foetal testis, 17 and 18 weeks of age, was studied with histochemical techniques for lipids in relation to steroid hormone synthesis. The vascularized interstitium consists of undifferentiated mesenchymal cells and differentiated or “luteinized” Leydig cells; the latter develop the histochemical features of well-established, actively secreting steroid gland cells of mature gonads, i.e., abundant, diffuse, sudanophilic lipoproteins and some phospholipid granules. The functional significance of these histochemical features, which are lacking in the undifferentiated stromal elements, is discussed in relation to steroid hormone biosynthesis in light of recent research in mature gonads of mammals and non-mammalian vertebrates. These comparisons suggest that the Leydig cells of human foetal testis are the active steroid secretors as a result of strong HCG stimulation. This also correlates well with previous electron microscopic and biochemical data on the human foetal testis. Besides actively secreting Leydig cells, there are also some degenerating ones which have become refractory to gonadotrophic stimulation as they have accumulated coarse lipid droplets consisting mainly of triglycerides, cholesterol and/or its esters, and very little phospholipid.
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  • 18
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    Cell & tissue research 152 (1974), S. 239-252 
    ISSN: 1432-0878
    Keywords: Ultrastructure ; Xenopus laevis ; Histochemistry ; Subcommissural organ (SCO)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructural features of the subcommissural organ (SCO) cells in larvae (stages 56–58, according to Nieuwkoop and Faber, 1956), toadlets (3 months after metamorphosis) and older toads (2-year old) of Xenopus laevis are described. Several age-related morphological differences in the endoplasmic reticulum (ER) of the SCO cells have been found. In old toads the rough ER assumes a special “ladder-like” membrane configuration in its cisternal lumen. By means of the periodic acid-chromic acid-silver methenamine (PA-CrA-SM) method, complex carbohydrates are detected electron microscopically in the SCO cells. Positive reactions take place in the cell adhesive apparatus, the secretory granules, part of the Golgi complex, and the intracisternal “ladder-like” structure. Passing through the Golgi complex, the secretory products mature into the secretory granules by association of their proteinaceous component with polysaccharides. The majority of the secretory granules are released from the apical cell surface by means of reverse pinocytosis, while the rest are released through the basal process into the blood circulation.
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  • 19
    ISSN: 1432-0878
    Keywords: Salivary glands ; Drosophila ; larval and prepupal ; Electron microscopy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A major function of the larval salivary glands of Drosophila melanogaster is known to be the production of a mucopolysaccharide that serves as an adhesive during puparium formation. In order to localize the mucosubstances during development substrate histochemical methods were used, and the site of acid phosphatase was demonstrated by the ultrahistochemical lead-salt method. It could be shown that the “glue”-granules in the corpus cells of larval salivary glands as well as the large secretion vacuoles in the prepupal corpus cells give a positive β-amylase-resistent PAS-reaction, which indicates neutral mucosubstances. Granular PAS-positive deposits in the larval and prepupal collum cells were reduced after preincubation with β-amylase and may represent glycogen, which has also been seen in electron micrographs of these cells. The Hale-reaction gave a weak indication that acid mucosubstances are present in the larval “glue” granules and in the large prepupal secretory vacuoles. After digestion of sialic acid with α-neuraminidase the weak indication was absent showing that the acid mucosubstances had been sialomucines. Ultrahistochemical demonstration of acid phosphatase indicated the presence of this enzyme in Golgi fields and lysosomal structures. Acid phosphatase seems to be missing in the large secretion vacuoles of the prepupal salivary gland. It is concluded, that the large vacuoles in the corpus cells of prepupal salivary glands represent a secretion product, obviously a mucosubstance. The lysosomal structures, containing acid phosphatase, may be accumulated in preparation for the autolysis of the gland which begins about two hours after the pupal moult, i.e. 15 hours after puparium formation.
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    Cell & tissue research 148 (1974), S. 417-429 
    ISSN: 1432-0878
    Keywords: Kidney ; Sexual segment ; Natrix natrix ; Histochemistry ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary The sexual segment of the kidney of Natrix natrix has been investigated cytochemically, light microscopically and ultrastructurally. The sexual segment, which seems to be an important accessory sexual organ, has a single layer of a columnar epithelium. The epithelial cells are filled with large secretion granules of a wide range of electron densities. Cytochemical reactions for neutral and acid mucosubstances are negative, but the cells show a strong positive staining for phospholipids. Within the cells of the sexual segment we have localised by histochemical means several hydrolases and oxydoreductases, which reflect enzyme activities of the glycolytic pathway, the citrate cycle, and related metabolic pathways. The activities of the hydrolytic enzymes acid phosphatase, acetylcholinesterase and indoxylacetate esterase are remarkably high within the epithelial cells. Furthermore it was found that the sexual segment tubules possess contractile elements which extends over the basal surface of the epithelial cells. These contractile cells exhibit a very high activity of alkaline phosphatase. Single unmyelinated axons are located between the contractile elements and the basal lamina of the sexual segment cells. The functional significance of the sexual segment structures is briefly discussed.
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    Cell & tissue research 147 (1974), S. 505-527 
    ISSN: 1432-0878
    Keywords: Cartilage ; Ageing ; Chondrocyte and matrix ; Light microscopy ; Histochemistry ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Histological, histochemical, and ultrastructural investigations have been carried out on ageing costal and tracheal cartilage of rats. The following age groups of animals have been studied: 1, 7, 14, 20, 30, 45, 75 days, 6 months, and 2 years. Ageing induces cellular changes which are represented by a reduction in the number of chondrocytes, a progressive increase in glycogen deposition, and processes of degeneration, the most frequent of which is the accumulation of lipidic material within large cytoplasmic vacuoles. Changes in the intercellular matrix become evident after 20 days in costal cartilage and after 30 days in tracheal cartilage. Chondroitin sulphate decreases while keratan sulphate, whose presence is limited to the territorial matrix, increases. Glycoproteins increase slightly in young animals and then remain constant; they decrease in the subperichondrial areas in old animals. Ultrastructurally, the matrix of cartilage of young animals contains thin collagen fibrils, most of which have no periodic banding. Roundish electron dense granules are associated with these fibrils. Irregular filaments associated with small electron-dense circular bodies are present around chondrocytes as well as within cytoplasmic vacuoles. With increasing age, and coincident with the reduction of chondroitin sulphate, the thickness of collagen fibrils increases, their period becomes evident, and the associated matrix granules decrease in number and size. Areas containing these fibrils undergo calcification, which frequently starts within roundish bodies of cellular origin. Collagen fibrils with a period of 640 Å but a highly variable thickness are often present in cartilage of adult and old rats. These fibrils seem to be due to an abnormal synthetic activity of chondrocytes.
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  • 22
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    Cell & tissue research 151 (1974), S. 347-368 
    ISSN: 1432-0878
    Keywords: Human thymus ; Hassall's corpuscles ; Histochemistry ; Electron microscopy
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    Topics: Biology , Medicine
    Notes: Summary Substrate-histochemical, enzyme-hystochemical and ultrastructural investigations were performed on thymic tissue from children, obtained in heart operations. β-Amylaseresistant, PAS-positive and Hale-positive substrates presumably neutral and acid mucosubstances, can be demonstrated in the central concentric lamellae of Hassall's corpuscles (HC). These lamellae also give positive reactions for sulphydryl groups and disulphide groups. Some flattened cell elements gave strong reactions for phospholipids, and small sudanophilic droplets, presumably neutral fats, are scattered throughout the HC. All investigated hydrolases and dehydrogenases either give no or only very weak reactions in the central part of progressive HC, but react strongly positive in their peripheral hypertrophic epithelial cells. In the central part of regressive HC, positive reactions for acid phosphatase and β-D-glucuronidase were recognized. These lysosomal enzymes may indicate degenerative processes. By electron microscopy progressive HC show central concentric lamellae with an amorphous matrix tightly filled with tonofilaments. They are surrounded by a thickened plasma membrane (200 Å), and do not contain nuclei. These central lamellae resemble the horny cells of the epidermis. The peripheral hypertrophic epithelial cells have pale nuclei with one or two nucleoli. Their cytoplasm contains numerous tonofibrils. These cells resemble stratum spinosum cells of the epidermis. In regressive HC the central concentric lamellae loose their intercellular contacts. The widened intercellular spaces are filled with cellular debris, and are invaded by macrophages. Similarities between the ultrastructure and the patterns of the histochemically investigated substrates and enzymes in human HC and epidermis are discussed.
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    Cell & tissue research 154 (1974), S. 121-129 
    ISSN: 1432-0878
    Keywords: Skeletal muscle ; Transplantation ; Androgen sensitivity ; Muscle regeneration ; Histochemistry
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    Topics: Biology , Medicine
    Notes: Summary The slow soleus muscle grafted into the bed of the fast, highly androgen sensitive levator ani (LA) muscle and innervated by the pudendal nerve, originally innervating the LA muscle acquires contraction and histochemical properties of the fast LA muscle. However, the “cross-transplanted” soleus muscle shows no changes in weight, contraction and histochemical properties after castration and testosterone application of 2 months duration. Thus the grafted soleus muscle is transformed into a fast muscle by foreign innervation, it does, however, not acquire androgen sensitivity, the latter being apparently primarily of myogenic origin.
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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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  • 26
    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 12 (1973), S. 169-173 
    ISSN: 1432-0827
    Keywords: Calcification ; Histochemistry ; Autoradiography ; Fetal ; Mandible
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des rats femelles reçoivent du45Ca ou du32P au 13ème et 18ème jour de la grossesse. Les coupes sériées des têtes de foetus sont étudiées par autoradiographie et par diverses méthodes histologiques pour déterminer la calcification. La détection la plus précoce de45Ca s'observe simultanément comme une réaction positive pour le calcium avec une des méthodes histologiques utilisées.32P est en évidence par les méthodes autoradiographiques un peu plus tard que le45Ca et sa présence coincide avec la réaction positive la plus précoce observée avec les autres méthodes histologiques utilisées. Les os de ces têtes foetales commencent à se calcifier selon un mode particulier commençant par la mandibule, puis l'os frontal et le maxillaire supérieur, suivis par les os nasaux, pariétaux et interpariétaux.
    Abstract: Zusammenfassung Weibliche Ratten erhielten45Ca und32P zwischen dem 13.–18. Tag der Schwangerschaft. Zur Ermittlung der Verkalkung wurden Serienschnitte der Köpfe ihrer Feten mittels Autoradiographie sowie durch verschiedene histologische Methoden untersucht. Das erste Auftreten von45Ca war ebenfalls von einer positiven Calciumreaktion mittels einer der verwendeten histologischen Methoden begleitet.32P wurde in der Autoradiographie erst etwas später als45Ca festgestellt und dessen Nachweis deckte sich mit den ersten positiven Reaktonen aller anderen verwendeten histologischen Methoden. Die Knochen in diesen Fetusköpfen begannen in einer bestimmten Sequenz zu verkalken: zuerst der Unterkiefer, dann das Stirnbein und der Oberkiefer, dann das Nasenbein, die Parietal- und Interparietalknochen.
    Notes: Abstract Female rats were given45Ca or32P from 13 to 18 days of pegnancy. Serial sections from the heads of their fetuses were studied by autoradiography, as well as by several histological methods for assessing calcification. The earliest detection of45calcium occured at the same time as a positive reaction for calcium with one of the histological methods used.32P was not detectable by autoradiographic methods until somewhat later than45Ca, and its presence coincided with the earliest positive reaction with all of the other histological methods employed. The bones in these fetal heads began to calcify in a partcular sequence, the mandible first, then the frontal bone and maxilla, followed by the nasal, parietal and interparietal bones.
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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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    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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  • 33
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    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of phenobarbital were measured in 18 newborn infants for one to two weeks after birth. The drug had been administered prenatally to the mothers as part of treatment for maternal hypertension or toxaemia. The plasma half-life of the drug in the infants (77–404 h) was inversely correlated with the extent of prenatal exposure to it. In three infants a bi-phasic plasma curve was found as there was a sudden change from slow to fast disappearance on the 5th to 7th day of life.
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  • 34
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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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    European journal of clinical pharmacology 6 (1973), S. 181-186 
    ISSN: 1432-1041
    Keywords: Phenothiazines ; thioridazine ; serum levels ; pharmacokinetics ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The rate of absorption of thioridazine varied greatly in ten healthy volunteers who took 100 mg in the morning after an overnight fast. The peak level in blood was also variable and it was reached 1 1/4 to 4 h after dosing. Maximal concentrations in the blood varied widely from 0.13 µg/ml to 0.52 µg/ml. No relation was found between the weight or sex of the subjects and the pharmacokinetics of the drug. The serum half life of thioridazine in three healthy volunteers was 9, 10 and 10 h respectively. In a group of 22 patients receiving less than 5 mg/kg body weight a day, there was a strong correlation between the dose and the morning or evening concentration of thioridazine in the blood. A positive correlation was also observed between the age of the patient and the serum level in those who received doses of less than 5 mg/kg body weight.
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    European journal of clinical pharmacology 6 (1973), S. 88-92 
    ISSN: 1432-1041
    Keywords: Noradrenaline pools ; 7-3H-noradrenaline ; neuro-effector junction kinetics ; pharmacokinetics ; sympathoadrenergic activity
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A two-compartment model of 73HNA distribution has been developed for studying sympatho-adrenergic activity in intact man. After infusion of 73HNA at constant speed in resting normal subjects, the decay curves of the plasma concentration and urinary excretion of 73HNA were plotted against time. Analysis of the curves yielded constants and indirect indications about noradrenaline exchange processes in the extracellular environment. Complete evaluation of the neuronal pools and of the pathways of biosynthesis and metabolism was impossible, but it seemed likely that 73HNA entered small neuronal pools that underwent rapid exchange with the extracellular environment, a point of some interest in clinical and pharmacologic investigations.
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    European journal of clinical pharmacology 6 (1973), S. 137-140 
    ISSN: 1432-1041
    Keywords: Urography ; Hypaque® ; Urovist® ; pharmacokinetics ; renal failure
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Comparative tests were carried out, using a radioactive tracer method, on the pharmacokinetics of sodium and methylglucamine diatrizoate. A biological model was simulated using an analogue computer; and the rate and elimination constants, the elimination half life, and the ratio of tissue entry to tissue elimination constants were calculated. Over the period of time required for X-ray diagnosis, the two salts of the contrast medium acid which were tested did not alter the pharmacokinetics of the contrast medium itself.
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    European journal of clinical pharmacology 6 (1973), S. 245-250 
    ISSN: 1432-1041
    Keywords: Procaine amide ; N-acetylprocaine amide ; sustained-release ; pharmacokinetics ; ventricular arrhythmia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with acute myocardial infarction were studied during treatment with either a conventional or a new sustained-release preparation of procaine amide in order to compare fluctuations in plasma concentration and urinary excretion of the drug during “steady state” conditions. Procaine amide in plasma was measured by spectrofluorimetry and the urine concentration of it and its major metabolite, N-acetylprocaine amide, by gas chromatography. The average fluctuation of plasma concentrations was 3.5±0.1 µg/ml during treatment with sustained-release tablets (dosage interval 8 h) and 4.2±0.4 µg/ml during treatment with ordinary tablets (dosage interval 4 h), i. e. it was 20% greater during treatment with the conventional preparation. There was no difference between the two preparations in recovery of the drug from urine (sustained-release tablets 85.4±3.0%; and conventional tablets 90.3±5.4%). Thus, the new sustained-release preparation of procaine amide administered 3 times daily produced the same range of plasma levels as the identical dose of conventional tablets given 6 times a day.
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    European journal of clinical pharmacology 6 (1973), S. 261-267 
    ISSN: 1432-1041
    Keywords: Alclofenac ; antiphlogistic ; man ; pharmacokinetics ; dosage regimes ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    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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    Cell & tissue research 136 (1973), S. 85-96 
    ISSN: 1432-0878
    Keywords: Liver ; Lampetra ; Physiological biliary atresia ; Electron microscopy ; Histochemistry
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    Topics: Biology , Medicine
    Notes: Summary A morphologic and histochemical study was carried out on the liver of larval and adult lampreys at the optical and electron microscopic level. In the larva the liver is composed of blind ending single cell thick tubules of hepatocytes. The tubular lumina provided with microvilli are morphologically comparable with the canalicular lumens of the higher species of animals. The cytoplasm of the hepatocytes contains numerous inclusions with heterogeneous appearance and crystalline material. The biliary system is composed of numerous bile ductules and ducts. In the adult lamprey, the biliary system has disappeared. The hepatocytes loose their tubular arrangement and the characteristic differentiation of their biliary pole. In contrast to previous reports in the literature the presence of bile pigment in the adult lamprey liver could not be demonstrated with any histochemical technique.
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  • 41
    ISSN: 1432-0878
    Keywords: Locus coeruleus (Rat) ; Neurons ; Golgi apparatus ; Catecholamine biosynthesis ; Histochemistry
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    Topics: Biology , Medicine
    Notes: Summary Detailed histochemical studies have been performed on the morphology of the Golgi apparatus (GA) by application of the thiamine pyrophosphatase (TPPase) method (Novikoff and Goldfischer, 1961) to the neurons of the locus coeruleus (LC) of normal and catecholamine biosynthesis inhibitors (fusaric acid and D, L-α-methyl-p-tyrosine methylester HCl) given adult healthy male Wistar strain rats. The neurons were classified into five categories on the basis of the morphology of the Golgi apparatus. The number of cells in individual categories was counted to evaluate the percentage of each category in the whole nucleus. The majority of cells belongs to Types II, III, and IV whose GA goes through cyclic activity, but the remaining neurons belong to Types I and V which may have a strong tendency to be different from the former in character. The latter neurons correspond formally with Types I and V of the rabbit LC, but they do not respond to the drugs administered. The rat LC is very similar to the dorsal vagal nucleus of the rabbit in regard to the dominant category. The present results indicate that the majority of the rat LC neurons may work vigorously and they may be motor neurons. Administration of the drugs caused reduction of TPPase activity, augmentation of disintegration and the budding-off process of the GA of Type IV, a decrease in the percentage of Type IV and an increase in that of Type II. Administration of 100 mg/kg fusaric acid caused maximal morphological change of the GA at the 90th minute; however, administration of 200 mg/kg fusaric acid showed more marked change of the GA, having two peaks and two valleys. The GA revealed much more intense reaction to D,L-α-methyl-p-tyrosine methylester HCl than to fusaric acid. The present results indicate that tyrosine hydroxylase may be the rate-limiting enzyme in the catecholamine biosynthesis. These noticeable changes of GA caused by administration of the drugs were completely restricted to the neurons of LC and the neurons of the mesencephalic nucleus of the trigeminal nerve did not show any morphological changes of the GA. These results strongly suggest that the GA of the rat LC neurons may have ability to synthesize catecholamine whereas the GA of the rat mesencephalic nucleus of the trigeminal nerve may be completely devoid of this ability and that the role of the GA may be different depending on the anatomical regions.
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    Cell & tissue research 139 (1973), S. 463-471 
    ISSN: 1432-0878
    Keywords: Gallbladder (Human) ; Mucus secretion ; Reverse pinocytosis ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Mucous secretory activity of the human gallbladder epithelium was investigated by light and electron microscopy and with histochemical techniques. There are two types of granules in the supranuclear region of the epithelial cells. The one low in density contains a fine filamentous material and gives a strongly positive silver methenamine reaction. The other is dense and only faintly positive. The granules of the former are considered to be mucous secretory granules and the granules of the latter may be lysosomes. PAS positive granules correspond presumably to both types of granules mentioned above. The mucous secretory granules are considered to be synthesized by the Golgi apparatus and the granular endoplasmic reticulum as has been confirmed in other mucous secretory cells. Their content is released from the cell by reverse pinocytosis. Typical goblet cells occur frequently in the fetal epithelium, but cannot be observed in the adult specimens.
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  • 43
    ISSN: 1432-0878
    Keywords: Hippocampal region (rat) ; Distribution of dehydrogenases ; Postnatal development ; Histochemistry ; Light microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Succinate-, α-glycerophosphate-, NADH-, and NADPH dehydrogenases (tetrazolium reductases) were studied histochemically in brain sections. The distribution of these enzymes in the hippocampal region was mapped in different postnatal stages. In addition to the hippocampus and the dentate area which have also been dealt with by other authors, the description includes the entorhinal area, parasubiculum, presubiculum, and subiculum. In all the areas of the hippocampal region the enzyme activity is first localized mainly in cell bodies. Activity in the neuropil shows a tendency to increase with age throughout the stages studied. Examples of particularly early or late differentiation of the histochemical pattern exist. Thus already after 4–6 days the differentiated staining pattern in the hippocampal layers as seen in the adult, begins to appear. In the entorhinal area the early enzyme distribution agrees with that in the adult and facilitates identification of its layers. After 22 days the fundamental enzyme chemoarchitectonics of the adult rat brain has been obtained. Histochemical characteristics of the different areas, support the view that the hippocampal region constitutes an entity.
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  • 44
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    Cell & tissue research 141 (1973), S. 375-400 
    ISSN: 1432-0878
    Keywords: Hippocampal region (rat) ; AChE distribution ; Postnatal development ; Histochemistry ; Light microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Acetylcholinesterase (AChE) in the hippocampal region was studied histochemically in different postnatal stages. Enzyme changes are described for the hippocampus proper, the dentate area, the entorhinal area, parasubiculum, area retrosplenialis e, presubiculum, and subiculum. In 1 day old animals there are only traces of AChE in solitary perikarya of the hippocampal stratum radiatum, while there is no activity in the neuropil. This is in contrast to other regions of the brain, e.g. the corpus striatum and the medial septum. Enzyme activity in the neuropil, although very weak, is seen clearly on the 2nd day. While the enzyme reaction in some cell soma seems to be permanent and also present in adult rats, other cell bodies, e.g. in the entorhinal area lose AChE activity during the last part of the 2nd week and in the 3rd week. Similar observations have been made on other parts of the central nervous system. The main features of chemodifferentiation in the hippocampal region seem to be completed by the end of the third week, although most layers and areas have not yet achieved the same high staining intensity as seen in the adult rats.
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  • 45
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    Cell & tissue research 141 (1973), S. 529-544 
    ISSN: 1432-0878
    Keywords: Osteoclast ; Parathyroid hormone ; Lysosomes ; Bone resorption ; Electron microscopy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Young rats were treated with high doses of parathyroid hormone (PTH). Osteoclasts from these animals revealed characteristic alterations in comparison to control cells: a) The cytoplasm contained large vacuoles with phagocytosed cells, some of which resembled osteoblasts or osteocytes. The vacuoles were interpreted as lysosomes because the engulfed cells often appeared partly digested and the vacuoles contained acid phosphatase as demonstrated histochemically, b) lipid droplets were present in the cytoplasm and usually located close to the endoplasmic reticulum and/or in regions with many free ribosomes, c) the Golgi complex was more frequently separated from the nuclei than in control cells, d) small coated cytoplasmic bodies were numerous in the peripheral cytoplasm, e) the membranes of the endoplasmic reticulum were fused in some places, f) cytoplasmic regions with numerous free ribosomes were frequent, g) large ring-shaped granules occurred in some mitochondria. Energy dispersive X-ray analysis of these granules provided evidence that they contained calcium and probably phosphorus, h) in some osteoclasts the mitochondria were enlarged. — The findings are consistent with an increased activity of osteoclasts and in particular a stimulation of the lysosomal system in these cells.
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  • 46
    ISSN: 1432-0878
    Keywords: Ovary (mouse) ; Granulosa cells ; Steroidogenesis ; Electron microscopy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A systematic study of Δ5-3β-hydroxysteroid dehydrogenase in the granulosa cells of immature and mature mice was made. The histochemical results were compared with the ultrastructural findings on the same cells in an attempt to determine whether the granulosa cells are capable of a steroidogenic role. In newborn and immature mice the granulosa cells of a great amount of follicles demonstrated a moderate or strong histochemical activity. In mature mice the granulosa cells demonstrated a weak or moderate activity normally only in preovulatory follicles and in some other atretic follicles. The granulosa cells of the normal developing follicles did not show such activity. In addition the histological control of numerous parallel sections demonstrated particularly in immature ovaries the presence of a great amount of atretic follicles. In the cytoplasm of the granulosa cells of the follicles in immature ovaries only clusters of lipid droplets with ribosomes were noted; while in the preovulatory follicles of mature animals there started to appear mitochondria with tubular cristae, smooth membranes of the endoplasmic reticulum and irregular lipid droplets. In the obviously atretic follicles several granulosa cells as well as theca interna cells showed numerous lipid droplets and ribosomes together with different degenerating organelles. The granulosa cells of the normal developing follicles showed a well developed Golgi complex, granular endoplasmic reticulum and free ribosomes. The histochemical and ultrastructural findings suggest a steroidogenic role of the granulosa cells only in the larger preovulatory follicles (probably related to an early luteinization of this layer) but this role was not demonstrated in the same cells in normal developing follicles. In addition, since an histochemical positivity was demonstrated also in the granulosa cells of some obviously atretic follicles, it is possible that many of the follicles having granulosa cells filled with lipid droplets and attached ribosomes and histochemically positive might be, in the immature ovaries, in a very precocious stage of atresia. It is to precise for these cells whether a cytoplasm with these two strictly correlated components (lipid droplets and attached ribosomes) and showing an histochemical positivity could carry-on all the biochemical steps involved in steroid biosynthesis or only has only a temporary capability to produce some precursors of steroids.
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  • 47
    ISSN: 1432-0878
    Keywords: Reproductive tract ; Biomphalaria glabrata ; Desiccation ; Starvation metabolism ; Weighing experiments ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of desiccation (36 weeks), starvation (12 weeks) and recovery (4 weeks following 16 weeks of desiccation and 2 weeks following 9 weeks of starvation) upon the accessory sex glands and some other body parts of Biomphalaria glabrata were studied by means of weighing experiments and histochemical and ultrastructural methods. The results of the weighing experiments show that the various parts of the reproductive tract are not protected from involution processes during the adverse conditions, as some parts (the albumen gland, spermduct and prostate gland) showed a more pronounced decrease in weight than other body parts. Measurements of the epithelial heights of the accessory sex glands and ultrastructural observations corroborate the results of the weighing experiments. During the adverse conditions the organelles involved in the formation of the secretion granules (granular endoplasmic reticulum and Golgi-apparatus) became involuted. The secretion granules within the cells of the albumen gland, spermduct and prostate gland were broken down by crinophagy. This latter process was less pronounced in the oviduct, muciparous gland, oöthecal gland, uterus and vagina. During the adverse conditions the lipoprotein producing cell types (mainly in the male part) remained active longer than the polysaccharide producing cell types (mainly in the female part). The significance of this observation is discussed. The amounts of glycogen present in most tissues of the reproductive tract and of the other investigated body parts (the foot, columellar muscle and vesicular connective tissue cells) were not apparently diminished, even when the secretory cells showed clear signs of involution, as a result of long periods of adverse conditions. Within the recovery periods 50% of the snails resumed egg production. During recovery the relative increases in weight of the accessory sex glands seemed to exceed that of other body parts, indicating that the restoration of the accessory sex glands is favoured. Histologically, reactivation of the accessory sex glands was apparent after 36–72 hours of recovery. At this time secretory material was again observed within the cisternae of the gland cell Golgi-bodies. Because reactivation is fairly rapid, a nervous or hormonal control of this process appears more likely than control via the general metabolism. The possible functions of various body organs in storing food reserve material is discussed, and it is concluded that the glycogen storing vesicular connective tissue cells (which occur throughout the whole body in the connective tissue) play a major role.
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  • 48
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    Cell & tissue research 144 (1973), S. 339-351 
    ISSN: 1432-0878
    Keywords: Nervous system ; Tissue culture ; Sheath cells ; Sensory end-organs ; Histochemistry
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    Topics: Biology , Medicine
    Notes: Summary Fetal spinal ganglia and spinal cord segments with adhering spinal ganglia were explanted on collagen-coated coverslips. They were investigated with enzyme histochemical methods for the existence of hydrolases and dehydrogenases up to 54 days of cultivation. Alkaline phosphatase was located in arachnoid cells and in mantle cells (satellite cells). Butyrylcholinesterase and alpha-glycerophosphate-menadione-tetrazolium reductase were found in mantle cells. Acetylcholinesterase and indoxylesterase were active in the whole neuron; acid phosphatase and alpha-naphthylacetate esterase were restricted to the perikarya. During the process of cell differentiation in vitro alkaline phosphatase decreased in mantle cells. Acid phosphatase became diminished distinctly in spinal ganglion cells. The other neuronal enzymatic activities remained unaltered during the whole period of cultivation. Proliferated Schwann cells were conspicuous by their activity for butyrylcholinesterase. In newly formed myelin sheaths arylsulphatase was active. Lactate dehydrogenase was contained in the perineurium which had developed. Cultures of long duration could contain cytological formations which were reminiscent of sensory end-organs with respect to their enzyme patterns. The enzyme activities of nervous tissues in vitro in their approximation to the situation in situ are discussed.
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  • 49
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    Cell & tissue research 142 (1973), S. 465-477 
    ISSN: 1432-0878
    Keywords: Rabbit thymus ; Ketosteroids ; Granulated cells ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Topochemisch konnten im Kaninchenthymus Ketosteroide nachgewiesen werden, für deren Vorhandensein die chemische Analyse von Thymuslipidextrakten Hinweise ergeben hatte. Die Darstellung der Ketosteroide erfolgte mit der NAHD-Reaktion (Camber, 1949). Diese Befunde dürften als spezifisch gelten, da eine Verfälschung durch freie Gewebsaldehyde, Plasmalogene (Gomori, 1952) und Corticosteroide (Khanolkar et al., 1958) ausgeschlossen wurde. Mit Hilfe der Camber-Methode konnten Granula bestimmter Zellen des Kaninchenthymus selektiv dargestellt werden, die auf Grund morphologischer Kriterien in zwei Gruppen unterteilt wurden. Die Zellen liegen im gesamten Thymusparenchym sowie im Bindegewebe der Septen und der sogenannten „Kapsel“. Prädilektionsorte stellen die Umgebung der Hassallschen Körperchen, die Mark-Rinden-Grenze, der intra- und perivasale Raum sowie die subkapsuläre Zone dar. Beide Zellgruppen sind Sudan III-, PAS- und Eosin-positiv, besitzen eine ausgeprägte gelbgrüne Eigenfluoreszenz und können differentialdiagnostisch gegen Mastzellen abgegrenzt werden. Elektronenmikroskopisch zeigen beide Zellgruppen zahlreiche Übereinstimmungen mit Reifestadien eosinophiler Knochenmarkszellen.
    Notes: Summary Ketosteroids were demonstrated topochemically in the rabbit thymus following indications given by chemical analysis of thymus lipid extracts. They were revealed by means of the NAHD-reaction (Camber, 1949). The results are thought to be specific, because adulteration by free tissue aldehydes, plasmalogens (Gomori, 1952) and corticosteroids (Khanolkar et al., 1958) can be excluded. The Camber-method selectively reveals the presence of two groups of morphologically differentiable granules in specific rabbit thymus cells which are distributed throughout the entire thymic parenchyme as well as in the connective tissue of the septa and the in so-called “capsule”. They are mainly seen in the vicinity of Hassall's bodies, in the zone between medulla and cortex, the intra- and perivascular space and in the subcapsular space. Both cell groups are Sudan III-, PAS- and eosin-positive, show intensive yellow-green primary fluorescence and can be distinguished from mast cells by differential diagnosis. Electron microscopy reveals that both cell groups show many similarities with the maturation phase of bone marrow eosinophils.
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    Cell & tissue research 145 (1973), S. 389-416 
    ISSN: 1432-0878
    Keywords: Adrenal chromaffin cells ; Ganglion cells ; Avian adrenal gland ; Light- and electron microscopy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of the adrenal gland of 15 bird species was investigated by light-, fluorescence-, and electron microscopy as well as by histochemical methods. 1. Adrenal Chromaffin Cells. Cells producing adrenaline (A) and noradrenaline (NA) may be distinguished from each other with the electron microscope by the different structure of their granules. In all species investigated A-cells prevailed. Granules in A-cells of Corvidae, partly those of the other passeriform birds as well, resemble granules from the pituitary pars intermedia because of their incomplete membrane and the low electron density of their contents. A-cells of some passeriform birds have mitochondria with specifically arranged cristae. Large cytosomes and inclusions of lipofuscin pigment are to be found in the gulls Larus ridibundus and Larus argentatus. The House Sparrow (Passer domesticus) and the Chaffinch (Fringilla coelebs) show vacuoles filled with a colloid-like substance, which are surrounded by adrenal chromaffin cells. 2. Ganglion Cells. The adrenal gland of birds is rich in ganglion cells. Two types can be distinguished. “Large” ganglion cells resemble completely sympathetic nerve cells as described in many vertebrates. “Small” ganglion cells have a low nucleus-cytoplasm-ratio. Some of them include granules of various structure and quantity. Whether they represent transitional stages to adrenal cells, interneurons, P-neurons or a heterogeneous population remains to be clarified.
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    Cell & tissue research 145 (1973), S. 417-442 
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    Keywords: Adrenal chromaffin cells ; Birds ; Cholinergic innervation ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary According to their ultrastructure and histochemistry three types of efferent nerve fibers can be distinguished in the bird's adrenal gland. The main part is made up of cholinergic fibers recognizable by a positive reaction for acetylcholinesterase and two specific populations of granules within the synaptic ending. Synaptic vesicles measuring 300 to 500 Å in diameter and dense-cored vesicles with a diameter of about 1 000 Å are discernible. In the periphery of the gland cholinergic axons for the innervation of adrenal cells form large bundles surrounded by a perineural sheath. The bundles cross the capsule and are situated within the adrenal chromaffin cords or at their periphery. Finally small groups of fibers enter a group of chromaffin cells which are surrounded by a basal lamina and which consist of about a dozen or more cells producing adrenaline and noradrenaline. Synaptic endings occur, above all in passeriform species, in the center of a chromaffin cell complex. They are either attached to the innervated cells or their dendrite-like processes, or embedded into the cells, or connected to short spines of the innervated cells. Synaptic and dense-cored vesicles leave the bouton by exocytosis. One synaptic terminal may innervate up to three A- or NA-cells. The existence of different types of synapses for A- and NA-cells cannot be excluded.
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  • 52
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    Keywords: Branchial gland ; Cephalopoda ; Fine structure ; Hemocyanin ; Histochemistry ; Electron microscopy
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    Description / Table of Contents: Zusammenfassung Licht- und elektronenmikroskopische Untersuchungen an der Branchialdrüse verschiedener Cephalopoden (Sepia officinalis, Octopus vulgaris, Loligo vulgaris, Eledone moschata) zeigen, daß das Drüsengewebe des stark vaskularisierten Organs aus einem sekretorisch aktiven Zelltypus mit ausgeprägtem endoplasmatischen Retikulum besteht. In den Zisternen des endoplasmatischen Retikulums lassen sich granuläre und ringförmige Strukturen (Durchmesser: 45–65 Å und 170 Å) nachweisen, die in Größe und Gestalt mit den Hämocyanin-Einheiten in den Gefäßen und Lakunen übereinstimmen und durch randlichen Zerfall der Zellen in den Blutraum auszuwandern scheinen. Die histochemischen Untersuchungen ergeben eine positive Reaktion für Monoaminoxydase, aber vergleichsweise geringe Phosphatase- und Dehydrogenase-Aktivitäten. Diese Befunde sowie der histochemisch nachgewiesene hohe Kupfergehalt des Drüsengewebes sprechen für eine hämopoetische, d.h. hämocyaninbildende Funktion der Kiemendrüse.
    Notes: Summary Light and electron microscopic investigations on the branchial gland of different Cephalopoda (Sepia officinalis, Octopus vulgaris, Loligo vulgaris, Eledone moschata) show that the gland tissue, strongly vascularized, consists of an actively secreting cell type with a remarkable endoplasmatic reticulum. In the cisternae of the endoplasmatic reticulum granular and ring-shaped structures can be identified (diameter: 45–65 Å and 170 Å) which correspond in size and shape with the hemocyanin units in the vessels and lacunae and which seem to emigrate into the blood space caused by the peripheral decay of the cells. Histochemical investigations show a positive reaction for monoaminoxidase, but comparatively low phosphatase and dehydrogenase activities. These results, and also the high content of histochemically identified copper in the gland tissue, seem to indicate a hemopoetic, i.e. hemocyanin-forming function for the branchial gland.
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  • 53
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    Keywords: Brain ; Hypothalamo-hypophysial system ; Xenopus laevis, tadpoles ; Monoamines ; Histochemistry
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    Topics: Biology , Medicine
    Notes: Summary In tadpoles of Xenopus laevis the histochemical distribution of monoamines in the tel-, di- and mesencephalon was studied. Catecholamines are present in some mitral cells of the olfactory bulb, the neurons of the preoptic recess organ (PRO), the neurons of the paraventricular organ (PVO) and cells in the vicinity of the PVO, namely the so-called PVO-accompanying cells, the nucleus infundibularis dorsalis (NID) and in the nucleus reticularis mesencephali (NRM). The PRO, PVO, and NID are composed of liquor-contacting neurons. With the Falck-technique, in the PVO and NID two types of fluorescent cells were observed: green cells, containing a catecholamine and yellow-orange cells, presumably containing a tryptamine. Tryptaminergic neurons occur in the NRM and in the area of the raphe nucleus. Extensive tracts of fluorescent fibres originating in the hindbrain ascend to the area praeoptica and the septum, striatum and epistriatum of the telencephalon. Also, fibre connections could be traced from the PVO to the area praeoptica, to the thalamus and to the nucleus ventromedialis tuberis. The PVO and/or NID give rise to a catecholaminergic tract running towards the hypophysis. Fibres of this tract partly terminate in the developing median eminence and partly in the pars intermedia. Experimental data indicate that the aminergic fibres in the pars intermedia exert an inhibitory influence on MSH-release.
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  • 54
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    Cell & tissue research 140 (1973), S. 91-100 
    ISSN: 1432-0878
    Keywords: Pulmonary and bronchial vessels ; Laboratory mammals ; Cholinesterase-containing nerve fibres ; Species differences ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Distribution of cholinesterase-containing nerve fibres on blood vessels in the lungs of rats, mice, rabbits, guinea pigs, cats, dogs, and rhesus monkeys has been studied with the thiocholine method modified by Coupland and Holmes and with the “direct-coloring” method according to Karnovsky and Roots. The presence of acetylcholinesterase positive nerve fibres on the pulmonary arteries has been established only in four species of the studied animals, namely the cat, the dog, the rhesus monkey and the rabbit. These nerves form d distinct plexus on the border between the media and adventitia. In the thick walled perihilar branches of the pulmonary artery of the rabbit the nerve fibres penetrate—as a rule—into the outer half of the media. Despite many times repeated experiments and careful investigations no nerve fibres have been found on the intrapulmonary branches of the blood vessels in the lungs of rats, mice, and guinea pigs. In the walls of the pulmonary veins, with the exception of the pulmonary veins in the rat and the mouse, cholinesterase fibres have been identified only seldom. Acetylcholinesterase nerve fibres in medio-adventitial localization have also been found in the walls of bronchial arterioles, this being the case in all the species under study. Bronchial veins do not exhibit any nerve fibres. The distribution of the acetylcholinesterase-containing nerve fibres on the pulmonary arteries is different from species to species.
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  • 55
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    Keywords: Neurosecretory cells ; Lateral ; Locust ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
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    Description / Table of Contents: Résumé L'étude histologique, histochimique et ultrastructurale des péricaryones neurosécréteurs latéraux de Locusta précise leur nombre et leur localisation. Elle révèle que le neurosécrétat latéral est semblable morphologiquement (forme et diamètre des granules élémentaires) au neurosécrétat A de la pars intercerebralis. Cependant, il en diffère histochimiquement par la présence d'une composante glucidique. Elle confirme l'hypothèse émise pour les péricaryones neurosécréteurs de la pars intercerebralis (Girardie et Girardie, 1967), de l'unicité cellulaire chez Locusta des types A et B selon la nomenclature de Johansson (1958). Elle suggère que les péricaryones latéraux pourraient être des cellules neurosécrétrices très actives.
    Notes: Summary The number (8 to 12) and position of the lateral neurosecretory cells have been established in Locusta by a histological, histochemical and ultrastructural study. The neurosecretory material of the lateral cells contains glycoprotein and is, in this way, histochemically different from medial A cells neurosecretory material. However, the morphological aspect (shape, diameter) of elementary dense core vesicles in the lateral and medial A neurosecretory cells is similar. This study confirms the idea (Girardie and Girardie, 1967) that, in Locusta, A cells and B cells (Johansson, 1958) are in fact two physiological aspects of one cell type. It also suggests that the lateral cells could be very active neurosecretory cells.
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    Cell & tissue research 146 (1973), S. 147-154 
    ISSN: 1432-0878
    Keywords: Peripheral autonomic innervation ; Ureterovesical ganglia ; Parasympathetic postganglionic synapse ; Sympathetic postganglionic synapse ; Denervated bladder ; Acetylcholinesterase ; Catecholamine ; Histochemistry
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    Topics: Biology , Medicine
    Notes: Summary Histochemical techniques for acetylcholinesterase and catecholamine show that ureterovesical ganglia of both cat and dog contain dense intraganglionic cholinergic and adrenergic plexuses. Ramifications of both plexuses surround most cholinergic and adrenergic ganglion cell bodies as pericellular synaptic plexuses. Similar pericellular plexuses exist around extraganglionic cholinergic and adrenergic ganglion cells. Both adrenergic and cholinergic synaptic fibers persist in denervated pregnaglionic nerve-free specimens, indicating that cholinergic synaptic fibers are postganglionic parasympathetic in nature. The presence of adrenergic (postganglionic sympathetic) and postganglionic parasympathetic synapses around cell bodies in ureterovesical ganglia provides a morphologic basis for the sympathoinhibitory and muscarinic parasympatho-excitatory phenomena described in these ganglia.
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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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  • 58
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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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  • 59
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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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  • 60
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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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  • 61
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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
    Source: Springer Online Journal Archives 1860-2000
    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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 63
    ISSN: 1573-8744
    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
    Source: Springer Online Journal Archives 1860-2000
    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. 49-57 
    ISSN: 1432-0827
    Keywords: Histochemistry ; Cartilage ; Enzymes ; Vitamin D ; Starvation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé 1. La distribution quantitative de phosphatase alcaline et de déshydrogénas eglucose-6-phosphate dans les zones hypertrophiques, en voie de prolifération du cartilage de rats rachitiques, pendant la cicatrisation induite par l'administration de vitamin D ou par jeun prolongé, est étudiée. 2. L'activité en phosphatase alcaline de la zone hypertrophique est environ triple de celle de la zone de prolifération du rat sevré normal et environ quadruple de celle des rats rachitiques. 3. Apres administration d'une seule dose de vitamine D (8000 unités), il se produit une augmentation significative de l'activité en phosphatase alcaline de la a zone en voie de prolifération. Une augmentation moins nette est observée dans la zone de prolifération de rats ayant jeuné 48 heures. 4. On observe une diminution significative de l'activité en phosphatase alcaline de la partie centrale de la zone hypertrophique de cartilage aprés traitement a la vitamine D. Une telle diminution n'a pas été observée chez le rat qui jeûne. 5. Chez le rat sevré normal, l'activité en déshydrogénase glucose-6-phosphate (G-6-PDH) est plus élevée dans la zone de prolifération que dans la zone hypertrophique. Chez le rat rachitique non traité, le contenu en enzyme est à peu pres identique dans les deux zones. 6. Apres traitement a la vitamine D, on note une décroissance nette de l'activité en G-6-PDH. Une telle décroissance n'est pas observée chez le rat qui jeûne.
    Abstract: Zusammenfassung 1. Diese Arbeit beschreibt die quantitative Verteilung der alkalischen Phosphatase und der Glucose-6-Phosphat-Dehydrogenase in proliferierenden und hypertrophischen Zonen von rachitischem Rattenknorpel während der durch Vitamin D-Gabe hervorgerufenen Heilung oder während der Mangeldiät. 2. Die Aktivität der alkalischen Phosphatase in der hypertrophischen Zone war etwa dreimal so groß wie in der proliferierende Zone der normalen entwöhnten Ratte und etwa viermal so groß bei den rachitischen Ratten. 3. Nach einer einmaligen Vitamin D-Gabe (8000 i.E) erfolgte eine signifikante Erhöhung der alkalischen Phosphatasen-Aktivität in der proliferierenden Zone. Eine weniger signifikante Erhöhung wurde in der proliferierenden Zone von Ratten festgestellt, welche 48 Std gefastet hatten. 4. Nach Vitamin D-Behandlung erfolgte eine signifikante Abnahme der alkalischen Phosphatasen-Aktivität in der mittleren Region der hypertrophischen Zone des Knorpels. Bei den fastenden Ratten wurde keine solche Abnahme beobachtet. 5. Bei der normalen entwöhnten Ratte war die Aktivität der Glucose-6-Phosphat-Dehydrogenase (G-6-PDH) größer in der proliferierenden als in der hypertrophischen Zone. Bei der unbehandelten rachitischen Ratte war der Enzymgehalt in beiden Zonen etwa gleich. 6. Nach Vitamin D-Behandlung erfolgte eine merkliche Abnahme der G-6-PDH-Aktivität. Bei der fastenden Ratte wurde keine solche Abnahme beobachtet.
    Notes: Abstract 1. The quantitative distribution of alkaline phosphatase and glucose-6-phosphate dehydrogenase in proliferating and hypertrophic zones of rachitic rat cartilage during healing induced by vitamin D administration or starvation is presented. 2. Alkaline phosphatase activity in the hypertrophic zone is about three times greater than that of the proliferating zone of the normal weanling rat and approximately four times greater in the rachitic rats. 3. Following a single dose of vitamin D (8000 I. U.) there was a significant elevation in alkaline phosphatase activity of the proliferating zone. A less significant increase was observed in the proliferating zone of rats which had breen fasted 48 hours. 4. There was a significant decrease in the alkaline phosphatase activity of the central region of hypertrophic zone of cartilage after vitamin D treatment. No such decrease was observed in the fasted rats. 5. In the normal weanling rat glucose-6-phosphate dehydrogenase (G-6-PDH) activity was greater in the proliferating zone as compared to the hypertrophic zone. In the untreated rachitic rat the enzyme content was about the same in the two zones. 6. Following vitamin D treatment there was an appreciable decrease in the G-6-PDH activity. No such decrease was observed in the fasted 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
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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    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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  • 69
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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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    European journal of clinical pharmacology 4 (1972), S. 191-195 
    ISSN: 1432-1041
    Keywords: Amobarbital ; pentobarbital ; barbiturates ; gas chromatography ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gas chromatographic methods are described for the assay of amobarbital and pentobarbital in 500 µl samples of plasma, in concentrations down to 250 ng/ml. After ether extraction at pH 5.5, the barbiturates are reextracted into an alkaline solution of trimethylanilinium hydroxide and are determined quantitatively by gas chromatography as their dimethylated derivatives. The method has been used successfully in volunteers receiving therapeutic doses of these bariturates.
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    European journal of clinical pharmacology 4 (1972), S. 137-141 
    ISSN: 1432-1041
    Keywords: Fentanyl ; pharmacokinetics ; neuroleptanalgesia ; analogue computer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and urinary excretion of3H-fentanyl were studied in 5 human subjects after intravenous injection of this drug. After an initial rapid decline, the plasma level of fentanyl decreased slowly and approximately exponentially. The plasma concentration of metabolites remained almost steady from 1–3 h after injection. More than 60% of the administered radioactivity was excreted through the kidneys within 4 days. Only a small proportion of it was unchanged fentanyl. The rates of fall of plasma concentration and of urinary excretion were slower in man than in rabbits. — The time courses of plasma concentrations and of urinary excretion were simulated on an analogue computer. The results support the assumption that the different time courses of concentrations in man and rabbits are caused by slower metabolism in man. It seems likely that redistribution plays a dominant part in the short duration of action of fentanyl in man.
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    European journal of clinical pharmacology 4 (1972), S. 150-157 
    ISSN: 1432-1041
    Keywords: Antibiotics ; pharmacokinetics ; microbiological assay ; drug control ; neonatal septicaemia
    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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  • 73
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    Cell & tissue research 126 (1972), S. 335-347 
    ISSN: 1432-0878
    Keywords: Glandulae submaxillares ; Mammals ; Duct cell granules ; Ultrastructure ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Discrete, PAS-positive granules of relatively uniform electron-density and size characterise the intercalated duct cells of mammalian submaxillary glands. Smaller, electron-dense organelles are seen in the cells at the junction of the intercalary-striated duct region in the guinea-pig. The large granules of variable electron-density which are observed in the proximal, modified intercalary cells in the rabbit closely resemble the granules in the acinar cells of the guinea-pig. Several populations of granules differing in size are found in the striated granular tubules of the rat and hamster; the organelles in the rat show two grades of electron-density whereas those in the hamster are uniformly dense. Numerous small granules with compactly arranged intragranular material occupy the apical part of the striated ducts of the cat, dog and rabbit. The chemical composition of each population of duct cell granules is unknown. The question whether granules containing kallikrein, trypsin-like enzymes and amylase are stored in the duct cells is discussed.
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    Cell & tissue research 131 (1972), S. 47-62 
    ISSN: 1432-0878
    Keywords: Neurohypophysis ; Lungfish ; Ultrastructure ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The neurohypophysis of the South American lungfish Lepidosiren paradoxa has been studied with light and electron microscopy, including the Falck-Hillarp technique for catecholamines. The pars nervosa hypophyseos is a well-marked, dorsally located subdivision of the pituitary gland composed of lobes or follicles, each one constituted of a central core of ependymal cells, a subependymal hilar region made up of nerve fibers and a peripheric palisade zone of nerve endings which contact capillary vessels. Four types of neurosecretory axons can be distinguished under the electron microscope. Type I, the most common, contains spherical elementary granules of high electron density, 1500–1800 Å in diameter. The scarce type II axons contain irregularly-shaped elementary granules. Type III contains only small clear vesicles, 400–600 Å in diameter. Type IV, mostly present in regions of the gland contacting the pars intermedia, contain large granulated vesicles, 900–1000 Å in diameter. The Falck-Hillarp technique revealed axons with a positive reaction for catecholamines at sites corresponding approximately to the location of type IV of the electron microscope. Ependymal cells are of large size, linking the cerebrospinal fluid, the nerve endings and the blood vessels. A conspicuous membrane-bound, spherical dense material, 1400–2000 Å in diameter, is observed in both the apical and vascular processes of these cells. The ependymal processes which traverse the hilar and palisade regions contain structures resembling degenerated neurosecretory axons. These results are discussed in relation with the currently available information on the comparative anatomy of the pars nervosa. The possible functional significance of ependymal cells and of each type of axon are also discussed. This study was aided by the following grants: NIH NS 06953 to Prof. De Robertis, Consejo Nacional de Investigaciones Científicas y Técnicas to Prof. Zambrano, Comisión de Investigaciones Científicas de la Provincia de Buenos Aires and Comisión de Investigaciones Cientificas de la Universidad Nacional de la Plata: to Prof. Iturriza. The authors are indebted to Prof. De Robertis for his generosity in granting us his laboratory facilities, and to Dr. F. J. J. Risso and Mr. A. Fernández (Resistencia, Chaco) who provided the specimens used in this study. The able microtechnical assistance of Miss L. Riboldazzi and Mrs. R. Raña and the photographic work of Mr. A. Saenz are much appreciated.
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    Cell & tissue research 131 (1972), S. 299-308 
    ISSN: 1432-0878
    Keywords: Testis, rat ; Myoid cells ; Androgens ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To study the regulation of the development of myoid cells, seminiferous tubules of adult and prepubertal rats were grown in organ culture under the influence of testosterone, HCG and cyproterone acetate. Contractility, EM-structure and histochemical activities of alkaline phosphatase and ATPase of the myoid cells were studied in the adult rat tubules at one week intervals up to 5 weeks in culture, in the prepubertal rat tubules at the age of 15 days and after 15 and 21 days in culture. As in vivo, contractions appear in cultured tubules of prepubertal rats at the age of 15 days. Testosterone and HCG increase the percentage of contractile tubules and the number of filaments of the myoid cells. Cyproterone acetate inhibits both functional and structural development and tends to decrease the enzyme activities. In the cultured adult rat tubules cyproterone acetate causes disappearance of contractility within one week, while contractions normally are found for 3 weeks. Testosterone and HCG have no notable effects on the contractility of adult rat tubules, but they lengthen the persistence of alkaline phosphatase activity. It is concluded that the maturation and also the functioning of the myoid cells are subject to androgenic regulation.
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    Cell & tissue research 131 (1972), S. 519-528 
    ISSN: 1432-0878
    Keywords: Cardiac innervation ; Teleosts ; Acetylcholinesterase ; Fine structure ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The innervation of the heart of the plaice has been studied ultrastructurally and histochemically in order to describe the anatomy, and the nature of the neuro-transmitters involved in the regulation of the heart. A single cardiac branch of the vagus runs over the Duct of Cuvier and sinus venosus where it forms a plexus extending into the sinoatrial region. Many ganglion cells are scattered throughout this plexus upon which are seen cholinergic-type terminals at which AChE can be localised. It is therefore concluded that this is the parasympathetic cardiac ganglion. The innervation of the atrium is dense at the sinoatrial end but decreases towards the ventricle. The ventricle is probably aneural, possibly a consequence of the lack of a coronary blood supply to act as a pathway for an innervation of this chamber. Most of the intramural axon profiles contain large numbers of small agranular vesicles and are cholinergic, AChE being localised at their membranes. Other profiles contain small numbers of larger granular vesicles amongst the agranular vesicles but these are not adrenergic since these vesicles are not depleted by reserpine, do not load with 6-OHDA, and AChE can be localised at the membranes of the profiles. No adrenergic-type profiles were seen in any part of the heart, nor were any fluorescent, catecholamine-containing fibres observed.
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    Cell & tissue research 134 (1972), S. 351-366 
    ISSN: 1432-0878
    Keywords: Sensory cell ; Proboscis ; Glycera convoluta ; Papilla ; Electronmicroscopy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Chaque papille de la trompe chez Glycera convoluta contient un groupe central de deux à quatre cellules sensorielles primaires. Chaque cellule possède un noyau allongé situé à mi-hauteur de la papille. Le processus péripherique ou dendritique porte cinq à six cils qui traversent la cuticule et sont entourés chacun par un cercle de microvillosités; les cils se prolongent dans le cytoplasme par de fines racines ciliaires qui se réunissent pour former une seule énorme racine montrant une striation périodique. Le processus central ou axonal se prolonge dans le plexus nerveux sous-épithélial. Le rôle physiologique de ces cellules est discuté.
    Notes: Summary Each papilla in the proboscis of Glycera convoluta contains a central group of two to four primary sensory cells. Each one shows an elongated nucleus situated at half-height of the papilla. The peripheric or dendritic process bears five to six cilia traversing the cuticle; each of them is circled by a ring of microvilli. The cilia are prolonged in the cytoplasm by fine ciliary rootlets which gather themselves in a very big single root showing a periodic striation. The central or axonal process runs in the subepithelial nervous plexus. The physiological role of the cells is discussed.
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    Cell & tissue research 131 (1972), S. 481-495 
    ISSN: 1432-0878
    Keywords: Hippocampal region ; Guinea pig ; AChE distribution pattern ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 1. The distribution of acetyl cholinesterase (AChE) has been described in the dentate area, a part of the hippocampal region, in the adult guinea pig. The enzyme was demonstrated histochemically with a modification of the Koelle thiocholine method applied to formaldehyde-fixed frozen sections and unfixed cryostat sections. Non-specific cholinesterase was suppressed by ethopropazine, while the staining reaction for AChE was controlled by complete specific inhibition with BW 284c51. A single brain was stained according to the method of Karnovsky and Roots. 2. The abundant AChE found in the dentate area exhibited a distinctly stratified distribution pattern. In the molecular layer, strong reaction was present in the outer third and immediately above the granular cell layer, the intermediate zone being light. The granular cell bodies were unstained. In the hilus, five layers showing alternating stronger and weaker reaction for AChE were recognizable. 3. In view of the opinions of Cajal, Lorente de Nó, and Blackstad criteria for the definition of the dentate area are discussed. The present results fit into a concept of a layered guinea pig hilus representative of one group of mammals (other members being rabbit, monkey, and man) differing morphologically from the non-layered hilus of rat and mouse. The distribution of metal in the guinea pig hilus supports the concept. 4. Possible structural correlates to the AChE are considered and a comparison with the distribution of AChE in the rat, reported earlier, has been made. In the molecular layer, the most striking difference was the heavy activity observed in the outer third in the guinea pig, where the content is moderate in the rat. The granular cell layer appeared virtually identical in both species. In the hilus the stratified pattern in the guinea pig, contrasting with the more diffuse distribution in the rat, essentially reflects the differing structural architectonics in the hilus of the two species.
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    Keywords: Jejunum (rat) ; Lactic acid perfusion ; Mucosal hypertrophy ; Histology ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung An weiblichen Wistarratten wurden die zellulären und strukturellen Veränderungen der Dünndarmschleimhaut nach chronischer MS-Belastung durch 12tägige Dauerinfusion ins Jejunum untersucht. Folgende Befunde wurden erhoben: 1. Die MS-Belastung führt in Abhängigkeit von der Konzentration zur Reduktion des Glukosetransports. 2. Die Funktionsstörung ist bedingt durch Enzymaktivitätsverlust. 3. Die Reduktion betrifft alle enzymhistochemisch untersuchten Aktivitäten; sie zeigt, daß alle Zellkompartimente des Epithels beeinträchtigt sind. 4. Qualitative Abweichungen des Reaktionsmusters treten nach MS-Belastung nur beim Saure-Phosphatase-Nachweis auf. Sie sind gekennzeichnet durch Schwund der Markierbarkeit lysosomaler Granula und Auftreten einer schwachen, diffusen cytoplasmatischen Aktivität. 5. Die Schleimhaut unterliegt einer von der MS-Konzentration abhängigen Transformation mit Verschiebung der Zottenhöhen und Kryptentiefen. Sie wird begleitet von einer gesteigerten mitotischen Aktivität als Folge erhöhter Zellexfoliation an der Zottenspitze. Es handelt sich bei dieser Veränderung somit um eine Schleimhauttransformation vom hyper-regeneratorischen Typ. Ihr Initialstadium ist eine Hypertrophie, ihr Endstadium die zottenlose Schleimhaut mit stark veränderten Krypten. Das Endstadium wird unter MS-Belastung nicht ausgebildet, da geringe Konzentrationssteigerungen zu lokaler Gewebsschädigung und Darmperforation führen. 6. Das MS-Modell ist wegen seiner geringen experimentellen Breite ungeeignet für die biochemische Nacharbeitung der bei der einheimischen Sprue beobachteten cytochemischen Epithelveränderungen.
    Notes: Summary Cellular alterations and mucosal changes in zonation of the small intestine have been studied after prolonged perfusion (12 days) with lactic acid in the rat. These investigations were carried out with cytochemical methods using marker enzymes to study in detail the different stages of mucosal transformation of the hyperregenerative type. Results. 1. Lactic acid produces a dose-dependent reduction in glucose absorption and this is due to alterations of the absorptive epithelium. 2. The normal zonation of the small intestinal mucosa is changed. The degree and pattern of the alterations is dose-dependent. Mucosal hypertrophy—i.e. increase of villus height, crypt length and mitotic activity—is the initial stage of this process. 3. Both, cellular alterations and mucosal changes in zonation are the expression of strong compensatory activities in response to predominantly intraluminal stress. The relationship between mucosal hypertrophy after intestinal resection and mucosal transformation of the hyperregenerative type as induced by lactic acid infusion is discussed. 4. In view of its very limited experimental range the lactic acid model cannot be recommended for the study of the epithelial changes in mucosal transformation at a biochemical level.
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    Cell & tissue research 124 (1972), S. 445-453 
    ISSN: 1432-0878
    Keywords: Tactile hair system ; Snout ; Shrew ; Histology ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The structure of the snout and tactile hair system of the common shrew (Sorex araneus) and the distribution of cholinesterase and alkaline phosphatase activity were studied. The structure of the vibrissae is exceptional compared with that of other mammals studied. Differences are the attachment system of hair follicle to the capsule, the impossibility of dividing the blood sinus clearly into cavernous sinus and ring sinus, the lack of continuous ring-wulst, clear constriction in the outer root sheath at the neck of hair follicle and some specialized structures connected with this. Alkaline phosphatase was not found in the nervous structures of the vibrissae but cholinesterase activity occurs at least in two different structures upon or in the outer root sheath of the hair follicle. The role of these structures and the significance of vibrissae to the shrew is discussed.
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  • 81
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    Cell & tissue research 128 (1972), S. 457-469 
    ISSN: 1432-0878
    Keywords: Liver ; Amphibian ; Tissue culture ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two distinct types of cells were derived from organ cultures of liver from adult and larval Xenopus laevis. Each type was isolated in clonal cell culture. Several media were compared with respect to support of epithelioid outgrowths from explants and support of growth of epithelioid colonies in cell culture. Ultracentrifuged embryo extract promotes the growth of all cell types, but the particulate fraction is also required for the maintenance of the epithelioid morphology of larval cells. In these media it was possible to maintain some epithelioid cell cultures for over 6 months. The identity and retention of some specialized functions of both cell types were demonstrated on larval cells. One cell type contained PAS-stainable, amylase-sensitive granules that increased in amount after treatment with glucocorticoids. This same type was shown by histochemical methods to contain phosphorylase, glucose-6-phosphatase, and dexamethasone-inducible tyrosine aminotransferase, and is considered to be a hepatocyte. The second type appears to be a sinusoidal cell, since it phagocytosed trypan blue and stained positively for acid phosphatase.
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  • 82
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    Keywords: Epidermis ; Snails (Lymnaea stagnalis, Biomphalaria pfeifferi) ; Histochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The epidermis and the associated subepidermal gland cells of the freshwater snails Lymnaea stagnalis and Biomphalaria pfeifferi were studied by means of histochemical and electron microscope techniques. The single cell layered epidermis is composed of general epidermal cells, cilia cells and a few scattered goblet cells. The foot sole and the epidermal regions of the pneumostome and the ventral surface of the lips near the mouth consist nearly entirely of cilia cells; elsewhere the cilia cells are found scattered among the general epidermal cells. The apical layer of the general epidermal cells bear microvilli. Numerous mitochondria, vesicles and lysosomes are located in the apical region of the cells. Several Golgi bodies and a poorly developed granular endoplasmic reticulum occur in the supranuclear region; the nucleus lies in the basal part of the cell. The general epidermal cells in the mouth region contain numerous microfilaments compared to the general epidermal cells in the rest of the epidermis. The cilia of the cilia cells in the densely ciliated regions possess well developed roots and basal bodies interconnected by means of the basal feet. With regard to the other cell organelles, cilia cells are quite similar to the general epidermal cells. For comparison a brief study of the ultrastructure of the epidermis of the terrestrial snail Helix aspersa was carried out. The skin of the snail is covered by a mucous layer produced by various gland cells. In L. stagnalis, in addition to the epidermal goblet cells, thirteen subepidermal gland cell types could be distinguished. The histochemistry of the gland cell types is reflected in the ultrastructure. Three of the gland cell types have an ubiquitous distribution, four types are peculiar to the foot, two types to the lips and five types to the mantle. In B. pfeifferi one epidermal gland cell type and only seven subepidermal gland cell types could be distinguished. Most of these gland cells are limited in their distribution to the foot, lips and mantle edge. The observations may provide a basis for further study in the functions of the snail epidermis.
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  • 83
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    Cell & tissue research 130 (1972), S. 205-218 
    ISSN: 1432-0878
    Keywords: Sternal gland ; Trinervitermes geminatus ; Cell types ; Histochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé La glande sternale de Trinervitermes geminatus correspond à un épaississement médian de la partie antérieure du cinquième sternite abdominal. Elle est bordée intérieurement par une fine basale conjonctive et extérieurement par la cuticule, quelques sensilles campaniformes sont également visibles dans la masse glandulaire. On peut y reconnaître deux types de cellules: d'abord des cellules ovalaires situées dans la partie moyenne de la glande. Elles contiennent de grosses mitochondries et des globules denses, et sont en relation avec la basale par quelques fins prolongements cellulaires. Ensuite des cellules cylindriques, bien développées, constituant toute l'épaisseur de la glande. Elles possèdent de nombreuses vésicules de reticulum lisse et une bordure en brosse formée de microvillosités et de digitations cytoplasmiques qui pénètrent dans la cuticule. Cette cuticule comprend une mésocuticule lacunaire et une fine épicuticule percée par des «canalicules épicuticulaires». Une comparaison est établie avec la glande sternale d'autres termites, en particulier celle de Kalotermes.
    Notes: Summary The sternal gland of Trinervitermes geminatus appears as a median thickening of the epidermis at the anterior part of the fifth abdominal sternite. It is lined internally with a thin basal lamina and externally with the cuticle. A few campaniform sensilla are also visible in the glandular mass. Two types of cells may be recognized. First, oval-shaped cells, containing numerous large mitochondria and dense globules; these cells having no contact with the cuticle are connected with the basal lamina by a few narrow cytoplasmic stems. Second, tall columnar cells, with vesicular endoplasmic reticulum and an apical brush border built up by microvilli and finger—like processes which reach into the cuticle. This cuticle is made of alveolous mesocuticle and a thin epicuticle perforated by “epicuticular canals”. The organ is compared with the sternal gland of other termites, particularly with the one of Kalotermes.
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  • 84
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    Cell & tissue research 133 (1972), S. 223-230 
    ISSN: 1432-0878
    Keywords: Harderian gland ; Anas platyrhynchus ; Polysaccharides ; Histology ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The parenchyma of the Harderian gland of the domestic duck consists of numerous tubular terminal portions, lined by a simple columnar epithelium. Its secretory surface is increased by intratubular folds. Within the cytoplasm of the epithelial cells secretory granules are observed. Polysaccharides of different nature are demonstrated. Strikingly, all centrally located cells contain a periodate reactive mucin. The successive administration of the PAS reaction and of Alcian Blue reveals the coexistence of acid and neutral mucins in the same cells. A metachromatic reaction of the mucosubstances at pH 1.0 was observed and the presence of acid sulfated groups in the Harderian gland, as demonstrated byAlcian Blue at pH 0.5, thereby confirmed. There was no glycogen reaction.
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  • 85
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    Cell & tissue research 134 (1972), S. 403-410 
    ISSN: 1432-0878
    Keywords: Small intestine (rat) ; Transport of peroxidase ; Epithelium ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Bei Ratten tritt 3 min nach intravenöser Injektion von Peroxydase elektronenmikroskopisch ein entsprechendes Reaktionsprodukt im Kapillarlumen der Lamina propria des Dünndarms und an der Basalmembrangrenze der Saumepithelzellen auf. 5 min nach der Injektion finden sich im basalen Abschnitt des Darmepithels pinozytotische Bläschen mit dem Peroxydase-Reaktionsprodukt. — 10–30 min nach der Injektion erreichen die Partikel die apikalen Teile der Zelle. Sie dringen in den interzellulären Spalten bis zu den Haftplatten vor, erreichen jedoch nie das Darmlumen. Im Dünndarm existiert vermutlich auch ein der Resorption entgegengesetzter Saftstrom, der durch Peroxydase markiert werden kann.
    Notes: Summary In rats, 3 minutes after intravenous injection of peroxidase the reaction product can be observed electronmicroscopically in the lumina of the capillaries of the small intestine as well as at the border of the basement membrane of the epithelial border cells. Pinocytotic vesicles containing peroxidase particles occur in the basal portion of the epithelium of the small intestine 5 minutes after injection. 10–30 minutes later, the peroxidase reaches the apical region of the cell. The particles infiltrate into the intercellular spaces as far as the tight junctions but never reach the intestinal lumen. In the small intestine there probably exists a flow of fluid in opposite direction to the resorption, which can be marked by peroxidase.
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  • 86
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    Cell & tissue research 124 (1972), S. 44-56 
    ISSN: 1432-0878
    Keywords: Axonal transport ; Toad spinal nerves ; Ligation ; Sympathectomy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The accumulation of both A and MAO proximal to a ligature on toad spinal nerves has been shown to occur at a slower rate than in mammals. As in mammals, there are two components of axonal transport in amphibian nerves, with the accumulation of A reaching a peak at between 4 and 7 days (cf. 2–4 days for NA in mammals), while MAO accumulation does not reach its maximum before 9 days (cf. 7 days in mammals). No accumulation occurs after sympathectomy, providing evidence for localization of MAO within amphibian sympathetic adrenergic nerves. Distal accumulation of MAO occurs in toad sympathetic nerves; this has not been reported to occur in mammalian nerves. Distal accumulation reaches a peak at 2–4 days, which suggests either a fast retrograde flow of MAO or that induction of MAO is occurring. These results are discussed in relation to differences between mammalian and amphibian sympathetic nerves and to the events occurring following ligation of these nerves.
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  • 87
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    Cell & tissue research 124 (1972), S. 433-444 
    ISSN: 1432-0878
    Keywords: Insect ; Fat body ; Development ; Protein body ; Electron microscopy ; Histochemistry ; Lipoprotein ; Cytology ; Lipid globule ; Silkworm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A developmental study at the electron microscopic level was conducted of the fat body cells of Hyalophora cecropia (L.). During the last larval instar the fat body increases in volume and the cells exhibit a well developed rough endoplasmic reticulum and protein bodies of diverse sizes. In the pupal fat body, the protein bodies appear to be enclosed by a double membrane and contain glycogen granules, ribosomes and mitochondrion-like structures. In addition, there are large lipid globules, cytolysomes and rough endoplasmic reticulum. The ultrastructure of the protein bodies suggests the development of large bodies by fusion of smaller protein bodies. Changes in fat body cell ultrastructure were followed during adult development and cytological evidence was obtained for the depletion of protein, glycogen and lipid in the female during this period. The female adult fat body cell contains free ribosomes, protein bodies, many mitochondria, a few lipid globules and glycogen granules. The male moth fat body cells have many mitochondria, a few glycogen granules, essentially no protein bodies, but an abundance of large lipid globules. Studies on the influence of egg maturation on the morphology of the fat body of Hyalophora gloveri (L.) revealed that ovariectomy of pupae yielded adults having more fat body than normal females, and that the fat body cells of the ovariectomized animals contained more glycogen, lipid and protein. Male pupae receiving ovarian implants developed into adults containing eggs and possessed more fat body than normal females but less than normal males. Very few glycogen granules were found in the fat body cells of normal males or males with implanted ovaries.
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    Cell & tissue research 126 (1972), S. 320-334 
    ISSN: 1432-0878
    Keywords: Glandulae submaxillares ; Mammals ; Acinar cell granules ; Ultrastructure ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Granules in acinar cells show considerable variations in size, shape, electron-density and molecular organisation of secretory material. Discrete organelles with an electron-dense homogenous matrix are seen in the guinea-pig and to some extent in the male hamster. Similar organelles with moderate electron-density are seen in the cat and dog. Acinar cells of the cat, hamster, guinea-pig and to a lesser extent the rat, contain discrete, pale granules and also confluent organelles arising from two to three of the pale particles. Composite, electron-pale secretory units are observed in the dog and rabbit. No correlation could be elicited between the histochemical reactivity of the acinar cells and the content of the secretory enzymes. The relationship between the histochemical reactivity and ultrastructural appearance of acinar cell granules and the organelles containing kallikrein, trypsin-like proteases and amylase seems much more important and functionally relevant. Morphological aspects of the intracellular transport and secretion of granules are discussed.
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  • 89
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    Cell & tissue research 124 (1972), S. 44-56 
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    Keywords: Axonal transport ; Toad spinal nerves ; Ligation ; Sympathectomy ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The accumulation of both A and MAO proximal to a ligature on toad spinal nerves has been shown to occur at a slower rate than in mammals. As in mammals, there are two components of axonal transport in amphibian nerves, with the accumulation of A reaching a peak at between 4 and 7 days (cf. 2–4 days for NA in mammals), while MAO accumulation does not reach its maximum before 9 days (cf. 7 days in mammals). No accumulation occurs after sympathectomy, providing evidence for localization of MAO within amphibian sympathetic adrenergic nerves. Distal accumulation of MAO occurs in toad sympathetic nerves; this has not been reported to occur in mammalian nerves. Distal accumulation reaches a peak at 2–4 days, which suggests either a fast retrograde flow of MAO or that induction of MAO is occurring. These results are discussed in relation to differences between mammalian and amphibian sympathetic nerves and to the events occurring following ligation of these nerves.
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  • 90
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    Keywords: Rectal caeca ; Starfishes ; Epithelium ; Histochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Dans les caecums rectaux des deux espèces étudiées, stratification tissulaire et composition cellulaire sont semblables. L'épithélium interne se compose de mucocytes et de cellules banales. Outre du glycogène, ces dernières renferment chez M. glacialis des grains de mucopolysaccharides neutres associés à des protéines tandis que chez C. tenuispina, les granules contiennent des mucopolysaccharides acides carboxylés et sulfatés également associés à des protéines. L'épithélium externe de C. tenuispina présente, outre des cellules banales, des cellules glandulaires à contenu protéique. Une attention particulière a été apportée à l'ultrastructure du pôle apical des cellules banales internes. On y remarque de nombreuses microvillosités et un flagelle central caractéristique. De plus, on observe très fréquemment des formations pinocytaires ainsi que plus rarement de la phagocytose. Les diverticules seraient donc, chez les Asteriidae, des organes digestifs à part entière se caractérisant par un grand pouvoir d'absorption et une digestion intracellulaire. Enfin, le pôle basal des cellules banales internes, très contourné, contient, par endroit, des β-cytomembranes typiques. Il est possible qu'à ce niveau aient lieu des transferts de substances vers le coelome.
    Notes: Summary Histological and cytological composition are similar in the rectal caeca of both studied species. Internal epithelium is composed of mucocytes and of banal cells. Besides glycogen, these cells contain in M. glacialis neutral mucopolysaccharides associated with proteins, while in C. tenuispina, the granules contain acidic carboxyled and sulfated mucopolysaccharides also associated with proteins. The external epithelium of C. tenuispina presents, besides banal cells, granular secretory cells with proteic content. Special attention has been payed to the ultrastructure of the apical pole of the internal banal cells. One notices numerous microvilli and a characteristic central flagellum. Moreover, one frequently observes pinocytic formations as well as—more rarely—phagocytosis. The rectal diverticula would thus be, in the Asteriidae, real digestive organs provided with a great capacity of absorption and intracellular digestion. The basal pole of the internal banal cells contains from place to place typical β-cytomembranes. Transfers of substances to the coelom can occur at that level.
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    Cell & tissue research 129 (1972), S. 561-569 
    ISSN: 1432-0878
    Keywords: Rumen epithelium (Goat) ; Permeability ; Transport of Myofer ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Durch submuköse Injektion von Myofer, einer licht- und elektronenmikroskopisch nachweisbaren Testsubstanz, wurde in vivo die Permeabilität des Pansenepithels untersucht. Folgende Befunde wurden erhoben: 1. Kurz nach der Applikation ist Myofer in allen Schichten des Epithels nachweisbar. Der Transport dieser Substanz ins Stratum corneum wird durch die tiefen Hornzellen der Barriere nicht verhindert. 2. In allen Epithelschichten ist das Myofer in Form intrazellulärer Cytosomen anzutreffen. 3. In den Interzellularräumen sind Myofergranula zwischen Basalmembran und den tiefen Hornzellen nur vereinzelt, zahlreicher jedoch jenseits der Barriere zu beobachten. Es wird gefolgert, daß die Testsubstanz Myofer die epitheliale Barriere durch transzelluläre Passage überwindet.
    Notes: Summary The permeability of the rumen epithelium to Myofer, a marker injected submucously in vivo, was studied in the light and electron microscopes. The following observations were made: 1. Myofer penetrates the ruminal epithelium 10 min after injection and can be found in all epithelial layers. The deep horny cells of the barrier layer do not prevent the penetration by this marker of the stratum corneum. 2. Myofer is present as cytosomes in cells of all epithelial layers. 3. The intercellular spaces between the basal lamina and the deep horny cells contain only few Myofer granules; the granules are more numerous on the other side of the barrier layer. The observations suggest that the marker Myofer passes through the epithelial barrier of the ruminal wall by transcellular passage.
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    Cell & tissue research 130 (1972), S. 455-462 
    ISSN: 1432-0878
    Keywords: Carotid body ; Cat ; ATPase ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Three kinds of nucleoside phosphatases were demonstrated histochemically in the cat carotid body with nucleoside triphosphate, nucleoside disphosphate and nucleoside monophosphate as substrates. Each of these enzyme activities exhibited the substrate specificity respectively. The nucleoside triphosphatase activity showed specific localization in association with the parenchymal cells of the carotid body. The electronmicroscopy revealed that the reaction product was located on and between the two apposing plasma membranes of type I and type II cells, of a type II cell and its wrapping axons and of the intricate basal infolding of a type II cell itself. Some possible functions of the adenosine triphosphatase in the carotid body are discussed.
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  • 93
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    Cell & tissue research 134 (1972), S. 227-243 
    ISSN: 1432-0878
    Keywords: Calcium cells ; Mollusca (Ferrissia wautieri) ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Le calcium s'accumule dans les tissues de Ferrissia wautieri sous forme de sphérules de calcaire intracellulaires. Notre travail comporte une étude descriptive de ces cellules en microscopie optique et électronique, et une étude minéralogique abordée par des techniques de coloration, de dissolution, de polarisation de la lumière et de diffraction électronique. Les résultats obtenus montrent que les sphérules, par leur aspect, leur nombre, leur volume et leur état de cristallisation, présentent des caractères différents selon la saison, ce qui permet d'établir une relation entre l'état des nodules calcaires et les variations du métabolisme des individus.
    Notes: Summary In Ferrissia wautieri calcium is stored in the connective tissue in intracellular calcareous spherules. The cells have been studied light- and electronmicroscopically and a mineralogical analysis of the spherules was done by selective staining, dissolution, polarisation and electron diffraction. The results of these studies show that the aspect, the number, the volume and the rate of cristallisation of the calcospherites are different according to the seasons. Therefore it may be assumed that the characteristics of the spherules are connected with metabolic variations in these animals.
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    Calcified tissue international 7 (1971), S. 267-276 
    ISSN: 1432-0827
    Keywords: Tech ; Development ; Enamel ; Enzyme ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'activité en naphtylamidase est étudiéc au niveau des incisives et molaires de rat, à divers stades de développement. Du L-leucyl-4-methoxy-2-naphtylamide, du L-alanyl-4-methoxy-2-naphtylamide, du L-leucyl-2-naphthylamide et du DL-alanyl-2-naphtylamide sont utilisés comme substrats: du bleu rapide B et du grenat rapide GBC sont employés comme sels de diazonium. Le naphtylamidase n'est pas visible au niveau de dents, en voie de dévelopment, au cours de la formation matricielle de l'émail. A la fin de ce stade, le naphtylamidase est présent au niveau de l'extrémité distale des améloblastes, près de la surface de l'émail. L'activité enzymatique reste identique jusqu'au moment de la fusion de l'épithélium dentaire et de l'épithélium buccal, au moment de l'éruption de la dent dans la cavité buccale. On ne rencontre pas de naphtylamidase au niveau d'autres tissues dentaires; cependant une activité marquée est observée dans les ostéoclastes au niveau des surfaces de résorption de l'os alvéolaire, entourant les dents, en voie de développement et d'éruption, et dans certaines régions du tissu conjonctif.
    Abstract: Zusammenfassung Die Aktivität der Naphthylamidase wurde in den Backen- und Schneidezähnen von Ratten in verschiedenen Entwicklungsstufen studiert. Als Substrate wurden L-leucyl-4-methoxy-2-naphthylamid, L-alanyl-4-methoxy-2-naphthylamid, L-leucyl-2-naphthylamid und DL-alanyl-2-naphthylamid verwendet; als Diazoniumsalze dienten Echtblau B und Echt-Granat GBC. Naphthylamidase konnte während der Schmelzmatrixbildung im Zahn nicht nachgewiesen werden. Nach Abschluß dieser Phase erschien Naphthylamidase in den distalen Enden der Ameloblasten, nahe bei der Schmelzoberfläche. Die Enzymtätigkeit blieb am selben Ort lokalisiert, bis das Zahnepithel, im Augenblick wo der Zahn in die Mundhöhle durchstößt, in das Mundepithel überging. Naphthylamidase wurde in anderen Zahngeweben nicht gefunden, aber eine deutliche Aktivität konnte in gewissen Bezirken des Bindegewebes sowie in den Osteoklasten der resorbierenden Oberflächen vom alveolären Knochen festgestellt werden, welcher die sich bildenden und die hervorstoßenden Zähne umgibt.
    Notes: Abstract Naphthylamidase activity was studied in rat molar and incisor teeth at different stages of development. L-leucyl-4-methoxy-2-naphthylamide, L-alanyl-4-methoxy-2-naphthylamide, L-leucyl-2-naphthylamide and DL-alanyl-2-naphthylamide were used as substrates and Fast blue B and Fast Garnet GBC as diazonium salts. Naphthylamidase was not demonstrable in the teeth during enamel matrix formation. After the termination of this stage, naphthylamidase was present in the ameloblasts in their distal ends close to the enamel surface. The enzyme activity retained this localization until the dental epithelium fused with the oral epithelium at the time of tooth eruption into the oral cavity. Naphthylamidase was not found in other dental tissues, but marked activity was found in osteoclasts at the resorbing surfaces of alveolar bone surrounding the developing and erupting teeth and in certain areas of the connective tissue.
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    European journal of clinical pharmacology 4 (1971), S. 54-58 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; infusion ; plasma expander ; blood level fluctuation ; sulfonamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary A hypothetical pharmacokinetic model is reported which describes the decreasing fluctuations in the blood levels of a sulfonamide during infusion of a plasma expander. Its concentration in the serum increases reciprocally with the amount of plasma expander infused. These procedures can be described by simple equations, and it is possible therefore, to calculate the dose required to maintain a constant blood level during the infusion.
    Notes: Zusammenfassung Es wird über ein hypothetisch-pharmakokinetisches Modell berichtet, welches sich mit der absinkenden Serumkonzentration eines Sulfonamids nach Infusion eines Plasmaexpanders beschäftigt. Die Serumkonzentration fällt reziprok zur infundierten Menge des Plasmaexpanders ab. Die Vorgänge lassen sich durch einfache Gleichungssysteme beschreiben. Es gelingt daher, eine Zusatzdosis zu berechnen, welche den bei Infusionsbeginn bestehenden Plasmaspiegel annähernd konstant erhält.
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    European journal of clinical pharmacology 4 (1971), S. 32-37 
    ISSN: 1432-1041
    Keywords: Glibenclamide ; pharmacokinetics ; metabolism ; potentiation of hypoglycemic action ; phenylbutazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary Metabolically healthy subjects were given an intravenous injection of 1,13 mg14C-labelled glibenclamide (HB 419). The plasma level, renal elimination of the radioactivity and metabolism of the substance were investigated. Two minutes after administration the HB 419 is virtually present only in the blood and at the end of the distribution period mostly in the extracellular space. 53% of the radioactivity is excreted via the kidneys in the form of metabolites. If glibenclamide is administrated in the same way to the same subjects after pretreatment with phenylbutazone there are no differences in the course of the plasma levels or the rate of elimination from the blood. There is, however, a significant difference in the excretion of the radioactivity in the urine. In the presence of phenylbutazone significantly less HB 419 metabolite is excreted renally. In view of the known alternative route of elimination it is suggested that the amount not excreted in the urine is in compensation eliminated via the bile. There was no difference in the metabolism of glibenclamide between the control and phenylbutazone treated groups. The potentiation by phenylbutazone of HB 419 action, and probably also that of other antidiabetic sulphonylureas, must therefore be due predominantly to other causes (Communication III).
    Notes: Zusammenfassung Stoffwechselgesunde Versuchspersonen erhielten14C-markiertes Glibenclamid in einer Dosis von 1.13 mg/Vpn i.v. gespritzt. Plasmaspiegelverläufe, renale Elimination der Radioaktivität und die Metabolisierung der Substanz wurden untersucht. Zwei Minuten nach der Applikation ist HB 419 praktisch nur im Blutund nach Abschluß der Verteilung weitgehend im Extracellulärraum vorhanden. 53% der Radioaktivität werden über die Nieren in Form von Metaboliten ausgeschieden. Wird den gleichen Probanden nach Prämedikation mit Phenylbutazon Glibenclamid in gleicher Weise verabfolgt, ergibt sich kein Unterschied hinsichtlich der Plasmaspiegelverläufe und der Eliminationsgeschwindigkeit aus dem Blut. Ein signifikanter Unterschied besteht jedoch in der Ausscheidung der Radioaktivität in den Harn (26.3%). In Gegenwart von Phenylbutazon wird ein signifikant geringerer Anteil von HB 419-Metaboliten renal eliminiert. Aufgrund des bekannten zweiten Ausscheidungsweges wird vermutet, daß der fehlende Anteil kompensatorisch über die Galle eliminiert wird. Die Metabolisierung von Glibenclamid weist keine Differenzen zwischen Phenylbutazon-und Kontroll-Gruppe auf. Die Wirkungspotenzierung von HB 419 — wahrscheinlich auch diejenige anderer antidiabetisch wirksamer Sulfonylharnstoffe — durch Phenylbutazon dürfte demnach überweigend andere Ursachen haben. (Mitteilung III).
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  • 97
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    European journal of clinical pharmacology 3 (1971), S. 221-228 
    ISSN: 1432-1041
    Keywords: Biguanides ; butylbiguanide ; pharmacokinetics ; sustained release form
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In man, after oral administration of 50 mg14C-butylbiguanide, the maximum serum concentration was 26–41 µg/100 ml. The biguanide was eliminated with an average half-life of 2h. 84% of the dose administered was found excreted unchanged in the urine. — After administration of14C-butylbiguanide in a sustained release form (Silubin® retard), the drug was slowly released and its serum concentration remained almost constant for up to 7 h.
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  • 98
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    Cell & tissue research 112 (1971), S. 15-30 
    ISSN: 1432-0878
    Keywords: Slug ; Biogenic amines ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of monoamines inLimax maximus was studied by the histochemical fluorescent method of Falck and Hillarp. The number of 5-HT-containing and catecholamine-containing perikarya in the central nervous system is small compared with the non-fluorescent perikarya. However, all the ganglia except the proto-cerebral ganglia have some amine-containing neurons. There are relatively larger numbers of fluorescent cells in the cerebral, visceral, pedal and right parietal ganglia than in the other ganglia. A single, giant 5-HT-containing neuron was observed in each meta-cerebral ganglion. Monoamine neurons are localised in a number of peripheral tissues (heart, integument, tentacles, penis retractor muscle, sole of foot, kidney, alimentary canal, reproductive organs and tentacular, pharyngeal and cephalic retractor muscles). Neurons containing catecholamine are mostly associated with sensory structures such as the statocysts, the retina of the eye and the integument of the tentacles, whereas 5-HT-containing nerve fibres are mainly observed in muscle tissues.
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  • 99
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    Cell & tissue research 116 (1971), S. 405-424 
    ISSN: 1432-0878
    Keywords: Midgut ; Formica ; Histophysiology ; Histochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Les cellules du mésentéron des ouvrières, des reines et des mâles de Formica polyctena F. possèdent un certain nombre de particularités cytologiques dont l'évolution a été suivie au cours du développement post-embryonnaire et du cycle annuel. A l'apex des cellules de régénération les microvillosités se différencient avant l'élimination des cellules caduques larvaires ou nymphales. A partir de la nymphose une activité sécrétoire apocrine se manifeste dans la partie dorsale de l'épithélium du mésentéron, l'ensemble des cellules assurant par ailleurs la fonction absorbante de l'organe. Il existe deux sortes d'inclusions cytoplasmiques, des polysaccharides et des concrétions minérales. Les polysaccharides sont surtout abondants chez les larves et les nymphes: le glycogène, polysaccharide de réserve, est utilisé au cours de l'histogénèse; des mucopolysaccharides acides, d'origine golgienne, représentent une sécrétion muqueuse. Les sphérocristaux sont constitués de strates concentriques de phosphates et chlorures de calcium et d'une matrice de mucopolysaccharides. La cristallisation des éléments minéraux s'effectue, à partir de la nymphose seulement, dans les citernes ergastoplasmiques. Cette accumulation d'ions pourrait être en relation avec le régime alimentaire de l'insecte ou représenter une voie d'excrétion.
    Notes: Summary The midgut cells of workers, queens and males of the ant Formica polyctena show cytological characteristics which were studied in the course of postembryonic development and annual cycle. The microvilli of the regenerating cells appear before the elimination of the regressing larval and pupal cells. At the time of pupation, an active phase of apocrine secretion begins in the dorsal part of the midgut epithelium, while the absorptive function is carried out by all cells of the organ. Two types of cytoplasmic inclusions coexist: polysaccharides and mineral concretions. The polysaccharides are particulary abundant in larvae and pupae. Glycogen is metabolized during histogenesis; acid mucopolysaccharides, elaborated in the Golgi apparatus, represent a mucous secretion. The spherites are composed of concentric strata of calcium phosphate and chloride and a matrix of mucopolysaccharides. These minerals form in the ergastoplasmic cisternae of pupal cells only. Their accumulation could be related to the insect's diet, or it could reflect a process of excretion.
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  • 100
    ISSN: 1432-0878
    Keywords: Notochord ; Caecilians ; Histochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The notochord of Ichthyophis glutinosus and I. kohtaoensis consists of peripheral flattened cells characterized by a well-developed system of rough endoplasmic reticulum, bundles of tonofilaments, and abundant glycogen particles. These cells contain furthermore fairly high activities of α-naphtyl-acetate esterase and 4-chloro-5-bromoindoxyl acetate esterase as well as acid phosphatase which was found in lysosomal localization. The huge intracellular vacuoles of the centrally situated cells possibly originate from electron translucent spaces within the glycogen fields of the peripheral cells. The notochord sheath consists of variously differentiated layers of collagen fibers and of an elastica externa. The diameters of the collagen fibers increase from the inner towards the outer region of the sheath. A peculiar feature of the Ichthyophis notochord sheath is a ring of mineralized collagen. The notochord of the caecilians investigated is compared with that of anurans, urodeles, and several groups of fish.
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